Artykuły w czasopismach na temat „Adjuvant”
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Bhatnagar, Noopur, Ki-Hye Kim, Jeeva Subbiah, Bo Ryoung Park, Pengfei Wang, Harvinder Singh Gill, Bao-Zhong Wang i Sang-Moo Kang. "Adjuvant Effects of a New Saponin Analog VSA-1 on Enhancing Homologous and Heterosubtypic Protection by Influenza Virus Vaccination". Vaccines 10, nr 9 (24.08.2022): 1383. http://dx.doi.org/10.3390/vaccines10091383.
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Adjuvants can increase the magnitude and durability of the immune response generated by the vaccine antigen. Aluminum salts (Alum) remain the main adjuvant licensed for human use. A few new adjuvants have been licensed for use in human vaccines since the 1990s. QS-21, a mixture of saponin compounds, was included in the AS01-adjuvanted Shingrix vaccine. Here, we investigated the adjuvant effects of VSA-1, a newly developed semisynthetic analog of QS-21, on promoting protection in mice after vaccination with the inactivated split virus vaccine. The adjuvant effects of VSA-1 on improving vaccine efficacy after prime immunization were evident as shown by significantly higher levels of hemagglutination-inhibiting antibody titers and enhanced homologous protection compared to those by QS-21 and Alum adjuvants. The adjuvant effects of VSA-1 on enhancing heterosubtypic protection after two doses of adjuvanted vaccination were comparable to those of QS-21. T cell immunity played an important role in conferring cross-protection by VSA-1-adjuvanted vaccination. Overall, the findings in this study suggest that VSA-1 exhibits desirable adjuvant properties and a unique pattern of innate and adaptive immune responses, contributing to improved homologous and heterosubtypic protection by inactivated split influenza vaccination in mice.
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Sayers, Samantha, Guerlain Ulysse, Zuoshuang Xiang i Yongqun He. "Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development". Journal of Biomedicine and Biotechnology 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/831486.
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Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used inBrucellavaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.
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Hsu, Shiou-Chih, Kun-Hsien Lin, Yung-Chieh Tseng, Yang-Yu Cheng, Hsiu-Hua Ma, Ying-Chun Chen, Jia-Tsrong Jan, Chung-Yi Wu i Che Ma. "An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection". Vaccines 12, nr 6 (23.05.2024): 569. http://dx.doi.org/10.3390/vaccines12060569.
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An incomplete Freund’s adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response. In contrast to α-galactosyl ceramide, its synthetic analogue C34 was antagonistic toward a stimulatory effect of an aluminum hydroxide adjuvant on a specific antibody response. The aluminum hydroxide adjuvant alone could confer complete vaccine-induced protection against mortality as well as morbidity caused by a lethal challenge of the same strain of an influenza A virus. The research results indicated that adjuvants could reshape immune responses either to improve vaccine-induced immunity or to provoke an unexpected pathogenic consequence. On the basis of these observations, this research connotes the prominence to develop a precision adjuvant for innocuous vaccination aimed at generating a protective immunity without aberrant responses.
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Volosnikova, E. A., D. N. Shcherbakov, V. V. Ermolaev, N. V. Volkova, O. N. Kaplina, M. B. Borgoyakova i E. D. Danilenko. "Development of a vaccine adjuvant based on squalene and study of its adjuvant properties". Medical Immunology (Russia) 25, nr 3 (1.06.2023): 685–90. http://dx.doi.org/10.15789/1563-0625-doa-2824.
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The use of modern subunit vaccines involves adjuvant introduction into their composition. Currently, the search for new and improvement of existing adjuvant systems is actively underway. Squalene- based adjuvants are well-known and approved in a number of countries for clinical use in influenza vaccines. Our study was devoted to the development of an adjuvant composition on the basis of squalene. The resulting adjuvants were composed in a form of oil emulsion containing a hydrophilic and hydrophobic phase. The stability of the emulsion was achieved by treating it with ultrasound at a frequency of 22 kHz. Particle sizes of the obtained emulsions were examined with the use of an electron microscope. The particle size was calculated to be 50-80 nm for the majority of particles (84%). Adjuvant activity was evaluated in 100 male Balb/C mice, weighing 16-18 g. To assess the humoral immune response, immunization was performed twice, with a 14-day interval, by intramuscular injection of 200 mL per animal. The receptor-binding domain (RBD) of the surface S protein of the severe acute respiratory syndrome coronavirus 2 (Delta variant (B.1.617.2)) or ovalbumin (OVA) from chicken eggs were used as antigens. RBD was administered at a dose of 50 mg/animal; OVA was administered at two doses (1 mg or 5 mg/animal). An antigen with aluminum hydroxide was used as a positive control; a saline solution was used as a negative control. The effectiveness of the obtained adjuvants was determined by measuring the titers of specific antibodies in mouse sera in ELISA assays using the recombinant RBD of SARS-CoV-2 S-protein or ovalbumin from chicken eggs. It was shown that the use of squalene-based adjuvants increased the antigens’ immunogenicity. The average titers of specific antibodies against RBD in the experimental group were 4 times higher than in the group immunized with RBD adjuvanted with aluminum hydroxide. An increase in immunogenicity of the antigen adjuvanted with squalene was also observed in the experimental OVA-group. Thus, it was shown that the developed squalene-based adjuvant compositions could be an alternative to the traditional adjuvants based on aluminum salts.
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Mancini, Rock, Aaron Hendricksen, Austin Ryan, Hector Aguilar-Carreno i Shahrzad Ezzatpour. "Modulating vaccine inflammation with thermophobic trehalose glycolipid adjuvant polymers". Journal of Immunology 210, nr 1_Supplement (1.05.2023): 158.04. http://dx.doi.org/10.4049/jimmunol.210.supp.158.04.
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Abstract Adjuvants drive the efficacy of many vaccines, however, they also elicit undesirable inflammation which is commonly pyrogenic resulting in local or systemic increases in temperature. Based on this, we envisioned that inversely coupling adjuvant potency to small (~2 °C) temperature changes could be a uniquely effective approach to balance efficacy while maintaining safety and tolerability. Here we report the first Thermophobic Adjuvant Polymers (TAPs) that reversibly attenuate potency in response to temperature. TAPs consisted of co-polymers containing both trehalose glycolipid adjuvant and thermoresponsive N-isopropylacrylamide (NIPAM) subunits. In an Influenza A/California/04/2009 virus vaccine mouse model, TAPs were effective adjuvants. Mice immunized with TAPs adjuvanted vaccine exhibited increased neuraminidase neutralizing antibodies, lymph CD4 +T cells, and CD4 +/44 +/62L +lung central memory T cells. Protection after viral rechallenge was comparable between TAPs and alum adjuvanted vaccines. At 37 °C in-vitro, TAPs elicited cytokine profiles comparable to other glycolipid adjuvants in the JAWSII cell line and primary CD11c +BMDCs. Relative to 37 °C, inflammation (TNF-α and IL-6) was enhanced at 35 °C and abrogated at 39 °C. DLS and NOESY-NMR suggest that the temperature-dependent activity is due to intramolecular hydrophobic shielding between the adjuvant and NIPAM which is enhanced beyond the lower critical solution temperature. Overall, this study demonstrates TAPs are an effective influenza vaccine adjuvant and elicit inflammation which is inversely linked to temperature. We envision this approach could be extended to many other adjuvants to enhance efficacy while maintaining safety and tolerability. Supported by grants from NIH (1R01CA234115), AAI (Careers in immunology fellowship), and the Washington Research Foundation.
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Isaacs, Ariel, Zheyi Li, Stacey T. M. Cheung, Danushka K. Wijesundara, Christopher L. D. McMillan, Naphak Modhiran, Paul R. Young, Charani Ranasinghe, Daniel Watterson i Keith J. Chappell. "Adjuvant Selection for Influenza and RSV Prefusion Subunit Vaccines". Vaccines 9, nr 2 (20.01.2021): 71. http://dx.doi.org/10.3390/vaccines9020071.
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Subunit vaccines exhibit favorable safety and immunogenicity profiles and can be designed to mimic native antigen structures. However, pairing with an appropriate adjuvant is imperative in order to elicit effective humoral and cellular immune responses. In this study, we aimed to determine an optimal adjuvant pairing with the prefusion form of influenza haemagglutinin (HA) or respiratory syncytial virus (RSV) fusion (F) subunit vaccines in BALB/c mice in order to inform future subunit vaccine adjuvant selection. We tested a panel of adjuvants, including aluminum hydroxide (alhydrogel), QS21, Addavax, Addavax with QS21 (AdQS21), and Army Liposome Formulation 55 with monophosphoryl lipid A and QS21 (ALF55). We found that all adjuvants elicited robust humoral responses in comparison to placebo, with the induction of potent neutralizing antibodies observed in all adjuvanted groups against influenza and in AdQS21, alhydrogel, and ALF55 against RSV. Upon HA vaccination, we observed that none of the adjuvants were able to significantly increase the frequency of CD4+ and CD8+ IFN-γ+ cells when compared to unadjuvanted antigen. The varying responses to antigens with each adjuvant highlights that those adjuvants most suited for pairing purposes can vary depending on the antigen used and/or the desired immune response. We therefore suggest that an adjuvant trial for different subunit vaccines in development would likely be necessary in preclinical studies.
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Lee, Youri, Eun-Ju Ko, Young-Tae Lee, Ki-Hye Kim, Young-Man Kwon i Sang-Moo Kang. "A unique adjuvant combination modulates immune responses preventing vaccine-enhanced pulmonary histopathology after vaccination with fusion protein and challenge with respiratory syncytial virus". Journal of Immunology 200, nr 1_Supplement (1.05.2018): 180.28. http://dx.doi.org/10.4049/jimmunol.200.supp.180.28.
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Abstract Vaccination of young children with alum-adjuvanted formalin-inactivated respiratory syncytial virus (FI-RSV) induced vaccine-enhanced disease (VED) after natural infection during epidemic season, resulting in hospitalizations and two deaths. There is no licensed RSV vaccine. VED was also observed in previous reports with fusion (F) protein RSV vaccines and adjuvants including oil-in-water emulsion, delta-inulin, and natural killer T cell agonist α-GalCer. In this study to search for adjuvants preventing RSV VED, we investigated a novel combination of monophosphoryl lipid A (MPL TLR4 agonist) and oligodeoxynucleotide CpG (CpG TLR9 agonist) in the RSV F protein vaccination. RSV specific IgG antibodies and neutralizing titers, and controlling RSV lung viral loads after challenge were similarly observed in the alum and MPL+CpG adjuvant groups of mice that received a single dose prime immunization with RSV F protein vaccine. Analysis of IgG isotypes and cytokines suggested the induction of T helper type 1 (Th1) immune responses by inclusion of MPL+CpG adjuvant in contrast to alum adjuvant biasing Th2 type immune responses. Most importantly, lung histopathology and infiltration of inflammatory innate immune cells (eosinophils, neutrophils) were not observed after F protein vaccination with MPL+CpG adjuvant whereas severe lung histopathology was induced after alum adjuvanted F protein vaccination and RSV challenge. The results in this study suggest a novel adjuvant approach to improve efficacy and safety of RSV subunit vaccines.
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Burakova, Yulia, Rachel Madera, Lihua Wang, Sterling Buist, Karen Lleellish, John R. Schlup i Jishu Shi. "Food-Grade Saponin Extract as an Emulsifier and Immunostimulant in Emulsion-Based Subunit Vaccine for Pigs". Journal of Immunology Research 2018 (27.11.2018): 1–8. http://dx.doi.org/10.1155/2018/8979838.
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Subunit vaccines consisting of highly purified antigens require the presence of adjuvants to create effective and long-lasting protective immunity. Advances on adjuvant research include designing combination adjuvants which incorporate two or more adjuvants to enhance vaccine efficacy. Previously, an oil-in-water emulsion adjuvant (OW-14) composed of mineral oil and an inexpensive gum Arabic emulsifier has been reported demonstrating enhanced and robust immune responses when used as an adjuvant in swine subunit vaccines. This study presents a modified version of OW-14 prepared with food-grade Quillaja saponin extract (OWq). In new OWq emulsion, saponin extract served as an emulsifier for stabilization of emulsion droplets and as an immunoactive compound. The use of saponins allowed to reduce the required amount of emulsifier in the original OW-14. However, emulsion stabilized with saponins demonstrated extended physical stability even at elevated temperature (37°C). The two-dose vaccination with a classical swine fever virus (CSFV) glycoprotein E2-based vaccine formulated with OWq produced higher levels of E2-specific IgG and virus neutralizing antibodies in pigs in contrast with animals that received the vaccine adjuvanted with oil only. In addition, new OWq adjuvant was safe to use in the vaccination of pigs.
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Yam, Karen, Jyotsana Gupta, Elizabeth Allen i Brian Ward. "Adjuvanted influenza vaccines in young and aged BALB/c mice (166.25)". Journal of Immunology 188, nr 1_Supplement (1.05.2012): 166.25. http://dx.doi.org/10.4049/jimmunol.188.supp.166.25.
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Abstract Although the available influenza vaccines are generally safe, they are far from ideal. They have reduced efficacy in the most at risk groups: the very young and the elderly. To address such concerns, the vaccine industry is increasingly turning its attention to the use of adjuvants to enhance the immune responses generated by these vaccines. During the 2009 pandemic H1N1 influenza outbreak, an adjuvanted influenza vaccine was selected for administration to Canadians; it was formulated with the oil-in-water adjuvant AS03 and consisted of 1/4 the usual antigen dose of vaccine. This study investigated the immune responses generated following immunization with adjuvanted influenza vaccines in aged and young mice. We tested two ages of BALB/c mice (2 months, 1.4 years), two doses of Influenza A/Uruguay H3N2 split vaccine (0.75ug, 3ug), and two adjuvants (alhydrogel, AS03). The use of an adjuvant increased serum HAI titers compared to vaccination with unadjuvanted vaccine. We found no significant difference in using the high dose of vaccine antigen with both adjuvants. At the low dose of vaccine, the AS03 adjuvant gave significantly higher HAI titers in both age groups. Finally, aged mice given a low dose of the AS03-adjuvanted split vaccine showed significantly lower HAI titers than young mice. We are identifying additional differences between the immune responses of young and aged mice with an overall goal to be able to design more effective vaccines, especially for the elderly.
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Sanchez, Pedro L., Greiciely Andre, Anna Antipov, Nikolai Petrovsky i Ted M. Ross. "Advax-SM™-Adjuvanted COBRA (H1/H3) Hemagglutinin Influenza Vaccines". Vaccines 12, nr 5 (24.04.2024): 455. http://dx.doi.org/10.3390/vaccines12050455.
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Adjuvants enhance immune responses stimulated by vaccines. To date, many seasonal influenza vaccines are not formulated with an adjuvant. In the present study, the adjuvant Advax-SM™ was combined with next generation, broadly reactive influenza hemagglutinin (HA) vaccines that were designed using a computationally optimized broadly reactive antigen (COBRA) methodology. Advax-SM™ is a novel adjuvant comprising inulin polysaccharide and CpG55.2, a TLR9 agonist. COBRA HA vaccines were combined with Advax-SM™ or a comparator squalene emulsion (SE) adjuvant and administered to mice intramuscularly. Mice vaccinated with Advax-SM™ adjuvanted COBRA HA vaccines had increased serum levels of anti-influenza IgG and IgA, high hemagglutination inhibition activity against a panel of H1N1 and H3N2 influenza viruses, and increased anti-influenza antibody secreting cells isolated from spleens. COBRA HA plus Advax-SM™ immunized mice were protected against both morbidity and mortality following viral challenge and, at postmortem, had no detectable lung viral titers or lung inflammation. Overall, the Advax-SM™-adjuvanted COBRA HA formulation provided effective protection against drifted H1N1 and H3N2 influenza viruses.
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Li, Junli, Lili Fu, Xiaonan Guo, Yang Yang, Jiaxin Dong, Guozhi Wang i Aihua Zhao. "Novel BC02 Compound Adjuvant Enhances Adaptive and Innate Immunity Induced by Recombinant Glycoprotein E of Varicella-Zoster Virus". Vaccines 10, nr 12 (15.12.2022): 2155. http://dx.doi.org/10.3390/vaccines10122155.
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Both adaptive and innate immunity responses are necessary for the efficient elimination of different pathogens. However, the magnitude, quality and desired type of immune response specific to the co-administered antigen is largely determined by adjuvants. BC02 (BCG CpG DNA compound adjuvants system 02) is a novel compound adjuvant with independent intellectual properties, which is composed of BCG CpG DNA biological adjuvant with Al(OH)3 inorganic salt adjuvant acting as a delivery system. Its safety and strong adjuvant efficacy have been effectively verified in preclinical and clinical trials (Phase Ib, ClinicalTrials.gov Identifier: NCT04239313 and Phase II, ClinicalTrials.gov Identifier: NCT05284812). In this study, we report the level of cell-mediated immunity (CMI) and humoral immune response induced by the BC02 novel adjuvant combined with different doses of varicella-zoster virus (VZV) glycoprotein E (gE) in a mouse model. In addition, we conducted preliminary in vitro experiments to explore the enhancement of RAW264.7 cell immune activity by BC02 adjuvanted-gE experimental vaccine to activate innate immune response. The results showed that the BC02-adjuvanted low, medium or high dose of gE were highly effective in eliciting both CMI and humoral immune responses to the immunized mice, respectively. The production of gE-specific IFN-γ and IL-2-specific T cells was established within 28 days after booster immunization. In particular, the effect of BC02-adjuvanted medium dose of gE has been shown to be more prominent. Meanwhile, fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests have also shown that the BC02 adjuvanted-medium dose of gE antigen could induce the secretion of neutralizing antibodies against clinically isolated VZV strains in mice. In addition, our findings have shown that 1/25 dose of gE+BC02 medium dose experimental vaccine can significantly induce the secretion of innate immune cytokines TNF-A, MCP-1, IL-6 and GM-CSF and up-regulate the costimulatory molecules CD40, CD80 and I-A/I-E on RAW264.7 cells; and it has also been activated to form M2 macrophages. At the same time, RAW264.7 cells were stimulated for 12 h, and their phagocytosis was significantly enhanced. Taken together, these results suggest that the BC02 compound adjuvant offers a strategy to induce an appropriate innate and adaptive immunity against the different doses of the VZV gE protein to improve subunit vaccine efficacy, and BC02 may be a promising adjuvant candidate for subunit HZ vaccines.
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Liu, Dong, Chaoqiang An, Yu Bai, Kelei Li, Jianyang Liu, Qian Wang, Qian He i in. "A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine". Viruses 14, nr 9 (24.08.2022): 1854. http://dx.doi.org/10.3390/v14091854.
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The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants.
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Ko, Eun-Ju, Young-tae Lee, Yu-Jin Jung, Youri Lee, Min-Chul Kim i Sang Kang. "A novel recombinant adjuvant replacing the CD4+ T helper cell functions in inducing IgG isotype antibodies and protection by T cell dependent influenza split vaccines (VAC8P.1052)". Journal of Immunology 194, nr 1_Supplement (1.05.2015): 144.8. http://dx.doi.org/10.4049/jimmunol.194.supp.144.8.
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Abstract The action mechanisms of adjuvants have not been well understood yet. We hypothesized that an effective adjuvant would overcome a defect in CD4+ T cell help for the induction of immune responses and protection by T cell dependent vaccines. We found that current influenza split vaccine was not able to induce antibodies and protection in a CD4+ T cell deficient condition. In an attempt to develop an effective adjuvant, we developed a recombinant virus-like particle expressing flagellin (FliC-VLP) and investigated its adjuvant effects and mechanisms by comparing alum adjuvant. CD4 knockout (CD4KO) mice that were immunized with influenza split vaccine plus FliC-VLP (or MF59, AS04 human adjuvant) induced IgG isotype-switched antibodies, germinal center formation, and virus-specific memory cells, all of which were not induced in CD4KO mice with split vaccine alone. Levels of antibodies and protective efficacy in CD4KO mice with split vaccine plus FliC-VLP were significantly higher than those in C57BL/6 wild type mice without adjuvant and CD4KO mice adjuvanted by alum. The adjuvanticity of FliC-VLP was partially dependent on TLR5 when tested in TLR5KO mice. Taken together, the results provide evidence that FliC-VLP adjuvant can stimulate the induction of antigen-specific immune responses and improve protection against lethal infection in CD4KO mice immunized with T cell dependent split vaccines, indicating CD4+ T cell independent action mechanisms of adjuvant.
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Feng, Huapeng, Makoto Yamashita, Li Wu, Tiago Jose da Silva Lopes, Tokiko Watanabe i Yoshihiro Kawaoka. "Food Additives as Novel Influenza Vaccine Adjuvants". Vaccines 7, nr 4 (24.09.2019): 127. http://dx.doi.org/10.3390/vaccines7040127.
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Influenza is a major threat to public health. Vaccination is an effective strategy to control influenza; however, the current inactivated influenza vaccine has mild immunogenicity and exhibits suboptimal efficacy in clinical use. Vaccine efficacy can be improved by the addition of adjuvants, but few adjuvants have been approved for human use. To explore novel and effective adjuvants for influenza vaccines, here we screened 145 compounds from food additives approved in Japan. Of these 145 candidates, we identified 41 compounds that enhanced the efficacy of the split influenza hemagglutinin (HA) vaccine against lethal virus challenge in a mouse model. These 41 compounds included 18 novel adjuvant candidates and 15 compounds with previously reported adjuvant effects for other antigens but not for the influenza vaccine. Our results are of value to the development of novel and effective adjuvanted influenza or other vaccines for human use.
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McMullan, Patrick M. "Emulsifier surfactant-oil combinations with tralkoxydim". Canadian Journal of Plant Science 73, nr 4 (1.10.1993): 1275–81. http://dx.doi.org/10.4141/cjps93-166.
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Research was conducted at the Brandon Research Station to determine the optimum oil-emulsifier surfactant ratio for each of two oil-emulsifier surfactant pairs for use with tralkoxydim. A series of adjuvants containing 8.5, 17, 34, and 68% emulsifier surfactant (by weight) plus oil were formulated for a petroleum oil (PO)- or methylated seed oil (MSO)-based adjuvant. Tame oats (Avena sativa L.) fresh weight was used to determine percent control as the indicator for phytotoxicity. PO (Sunoco 11 N oil) adjuvants had greater emulsion stability ratings than MSO adjuvants. Emulsion stability was not related to oats control, as MSO adjuvants enhanced tralkoxydim phytotoxicity more than PO adjuvants. Oats control increased as adjuvant volume increased from 0.25 to 2.0% (vol/vol) of the spray solution for either PO- or MSO-based adjuvants. For PO-based adjuvants, the adjuvant containing 34% emulsifier surfactant (by weight) and used at 0.5% (vol/vol) was as effective as the adjuvant containing 17% emulsifier surfactant and used at 1.0%. However, for MSO-based adjuvants, 17% emulsifier surfactant content was as effective as higher emulsifier surfactant content. Oats control did not correlate with the amount of oil in the spray solution. These data indicate that the optimum oil-emulsifier surfactant ratio will vary for each particular oil-emulsifier surfactant pair. Key words: Tralkoxydim, adjuvant, adjuvant volume, methylated seed oil, petroleum oil, surfactant content
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Wang, Zhi-Biao, i Jing Xu. "Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery". Vaccines 8, nr 1 (13.03.2020): 128. http://dx.doi.org/10.3390/vaccines8010128.
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Traditional aluminum adjuvants can trigger strong humoral immunity but weak cellular immunity, limiting their application in some vaccines. Currently, various immunomodulators and delivery carriers are used as adjuvants, and the mechanisms of action of some of these adjuvants are clear. However, customizing targets of adjuvant action (cellular or humoral immunity) and action intensity (enhancement or inhibition) according to different antigens selected is time-consuming. Here, we review the adjuvant effects of some delivery systems and immune stimulants. In addition, to improve the safety, effectiveness, and accessibility of adjuvants, new trends in adjuvant development and their modification strategies are discussed.
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Ji, Pengchao, Tiantian Li, Yanan Wu, Qi Zhao, Lu Li, Xuejian Shi, Wenting Jiang i in. "Virus-like Particle Vaccines of Infectious Bursal Disease Virus Expressed in Escherichia coli Are Highly Immunogenic and Protect against Virulent Strain". Viruses 15, nr 11 (30.10.2023): 2178. http://dx.doi.org/10.3390/v15112178.
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Objectives: Infectious bursal disease virus (IBDV) is a highly contagious, acutely infectious agent that causes immunosuppression in chickens. We expressed IBDV VP2 proteins in Escherichia coli (E. coli) to develop an effective virus-like-particles (VLPs) vaccine and evaluated its immunogenicity. Methods: The VLPs produced in E. coli were used as an immunogen mixed with a water-in-mineral-oil adjuvant (MontanideTM ISA 71 VG, ISA 71 RVG) or a white oil (7#) adjuvant. VLPs without an adjuvant, commercial subunit vaccine, inactivated vaccine, and attenuated vaccine were used as controls. These test vaccines were intramuscularly injected into 19-day-old SPF chickens, which were challenged with the IBDV virulent strain at 30 days after vaccination. Results: The adjuvants boosted antibody production, and the adjuvant groups (except white oil) produced higher antibody levels than the non-adjuvanted controls and the commercial vaccine groups. In terms of cellular immunity, the VLPs plus adjuvant combinations produced higher levels of cytokines, IL-2, IL-4, and IFN-γ than the controls. Conclusion: IBDV VLPs plus the ISA 71 RVG adjuvant can be used as an optimal vaccine combination for improving the immune efficacy of IBD subunit vaccines, which can protect against the virulent strain.
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Ryu, Ji In, Shin Ae Park, Seo Ri Wui, Ara Ko, Ji Eun Han, Jung Ah Choi, Man Ki Song, Kwang Sung Kim, Yang Je Cho i Na Gyong Lee. "A De-O-acylated Lipooligosaccharide-Based Adjuvant System Promotes Antibody and Th1-Type Immune Responses to H1N1 Pandemic Influenza Vaccine in Mice". BioMed Research International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/3713656.
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Vaccine adjuvants are agents that are used to promote immune responses to vaccine antigens and thereby to enhance the protective efficacy of the vaccines. In this study, we investigated the adjuvant activity of CIA06, an adjuvant system that is composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS) and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu-S® in mice. CIA06 significantly enhanced influenza-specific serum IgG, hemagglutination-inhibition, and virus-neutralizing antibody titers, which eliminated vaccine dose-dependency in the antibody response. Mice immunized with the CIA06-adjuvanted Greenflu-S showed Th1-type-predominant cytokine profiles, and both CD4+and CD8+T cell responses were induced. Immunization of mice with the CIA06-adjuvanted vaccine reduced the mortality and morbidity of mice upon lethal challenges with influenza virus, and no excessive inflammatory responses were observed in the lung tissues of the immunized mice after viral infection. These data suggest that the dLOS-based adjuvant system CIA06 can be used to promote the immune responses to influenza vaccine or to spare antigen dose without causing harmful inflammatory responses.
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Prior, J. Timothy, Christopher Davitt, Jonathan Kurtz, Patrick Gellings, James B. McLachlan i Lisa A. Morici. "Bacterial-Derived Outer Membrane Vesicles are Potent Adjuvants that Drive Humoral and Cellular Immune Responses". Pharmaceutics 13, nr 2 (20.01.2021): 131. http://dx.doi.org/10.3390/pharmaceutics13020131.
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Discovery and development of novel adjuvants that can improve existing or next generation vaccine platforms have received considerable interest in recent years. In particular, adjuvants that can elicit both humoral and cellular immune responses would be particularly advantageous because the majority of licensed vaccines are formulated with aluminum hydroxide (alum) which predominantly promotes antibodies. We previously demonstrated that bacterial-derived outer membrane vesicles (OMV) possess inherent adjuvanticity and drive antigen-specific antibody and cellular immune responses to OMV components. Here, we investigated the ability of OMVs to stimulate innate and adaptive immunity and to function as a stand-alone adjuvant. We show that OMVs are more potent than heat-inactivated and live-attenuated bacteria in driving dendritic cell activation in vitro and in vivo. Mice immunized with OMVs admixed with heterologous peptides generated peptide-specific CD4 and CD8 T cells responses. Notably, OMV adjuvant induced much greater antibody and B cell responses to co-delivered ovalbumin compared to the responses elicited by the adjuvants alum and CpG DNA. Additionally, pre-existing antibodies raised against the OMVs did not impair OMV adjuvanticity upon repeat immunization. These results indicate that vaccines adjuvanted with OMVs elicit robust cellular and humoral immune responses, supporting further development of OMV adjuvant for use in next-generation vaccines.
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Hauschild i Volkenandt. "Adjuvant treatment of malignant melanoma". Therapeutische Umschau 56, nr 6 (1.06.1999): 324–29. http://dx.doi.org/10.1024/0040-5930.56.6.324.
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Das Ziel einer adjuvanten Therapie nach operativer Entfernung eines Melanoms besteht in der Unterdrückung der Ausbreitung eventuell vorhandener, klinisch inapparenter Mikrometastasen. Vergleiche verschiedener Therapieverfahren (z.B. adjuvant applizierte Chemotherapeutika) mit unbehandelten Kontrollkollektiven ließen in der Vergangenheit gelegentlich eine Wirksamkeit erhoffen. Große, multizentrische, kontrollierte und prospektiv randomisierte Studien konnten jedoch keinen eindeutigen Vorteil einer adjuvanten Chemotherapie in bezug auf die Verlängerung der rezidivfreien Überlebenszeit oder der Gesamtüberlebenszeit erkennen. Eine adjuvante Zytostatika-Therapie kann daher außerhalb von klinischen Studien derzeit nicht mehr empfohlen werden. Derzeitige Hoffnungsträger sind insbesondere die rekombinant herstellbaren Zytokine, vor allem die Interferone. Drei große und randomisierte Studien zur adjuvanten Therapie mit Interferon-alpha von Hochrisiko-Patienten zeigten übereinstimmend eine verbesserte rezidivfreie Überlebenszeit; der Einfluß der Interferon-alpha-Behandlung auf die Heilungsraten bleibt jedoch weiterhin unklar. Ebenso kann derzeit zur optimalen Dosis und Dauer der Interferon-alpha-Therapie noch nicht eindeutig Stellung bezogen werden. Melanom-Patienten mit einem hohen Metastasierungsrisiko sollten in nationale und internationale prospektiv-randomisierte Therapieprotokollen eingeschlossen werden, deren Ergebnisse zu allgemeinverbindlichen Empfehlungen zur adjuvanten Melanomtherapie führen können.
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AbdelAllah, Nourhan H., Nourtan F. Abdeltawab, Abeer A. Boseila i Magdy A. Amin. "Chitosan and Sodium Alginate Combinations Are Alternative, Efficient, and Safe Natural Adjuvant Systems for Hepatitis B Vaccine in Mouse Model". Evidence-Based Complementary and Alternative Medicine 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/7659684.
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Hepatitis B viral (HBV) infections represent major public health problem and are an occupational hazard for healthcare workers. Current alum-adjuvanted HBV vaccine is the most effective measure to prevent HBV infection. However, the vaccine has some limitations including poor response in some vaccinee and being a frost-sensitive suspension. The goal of our study was to use an alternative natural adjuvant system strongly immunogenic allowing for a reduction in dose and cost. We tested HBV surface antigen (HBsAg) adjuvanted with chitosan (Ch) and sodium alginate (S), both natural adjuvants, either alone or combined with alum in mouse model. Mice groups were immunized subcutaneously with HBsAg adjuvanted with Ch or S, or triple adjuvant formula with alum (Al), Ch, and S, or double formulations with AlCh or AlS. These were compared to control groups immunized with current vaccine formula or unadjuvanted HBsAg. We evaluated the rate of seroconversion, serum HBsAg antibody, IL-4, and IFN-γlevels. The results showed that the solution formula with Ch or S exhibited comparable immunogenic responses to Al-adjuvanted suspension. The AlChS gave significantly higher immunogenic response compared to controls. Collectively, our results indicated that Ch and S are effective HBV adjuvants offering natural alternatives, potentially reducing dose.
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Shichinohe, Shintaro, i Tokiko Watanabe. "Advances in Adjuvanted Influenza Vaccines". Vaccines 11, nr 8 (21.08.2023): 1391. http://dx.doi.org/10.3390/vaccines11081391.
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The numerous influenza infections that occur every year present a major public health problem. Influenza vaccines are important for the prevention of the disease; however, their effectiveness against infection can be suboptimal. Particularly in the elderly, immune induction can be insufficient, and the vaccine efficacy against infection is usually lower than that in young adults. Vaccine efficacy can be improved by the addition of adjuvants, and an influenza vaccine with an oil-in-water adjuvant MF59, FLUAD, has been recently licensed in the United States and other countries for persons aged 65 years and older. Although the adverse effects of adjuvanted vaccines have been a concern, many adverse effects of currently approved adjuvanted influenza vaccines are mild and acceptable, given the overriding benefits of the vaccine. Since sufficient immunity can be induced with a small amount of vaccine antigen in the presence of an adjuvant, adjuvanted vaccines promote dose sparing and the prompt preparation of vaccines for pandemic influenza. Adjuvants not only enhance the immune response to antigens but can also be effective against antigenically different viruses. In this narrative review, we provide an overview of influenza vaccines, both past and present, before presenting a discussion of adjuvanted influenza vaccines and their future.
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Harrell, Jaikin, Lisa A. Morici i James B. McLachlan. "The use of outer membrane vesicles as novel, mucosal adjuvants against intracellular bactiera". Journal of Immunology 208, nr 1_Supplement (1.05.2022): 181.09. http://dx.doi.org/10.4049/jimmunol.208.supp.181.09.
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Abstract Many pathogens first enter the body via mucosal surfaces where they can then invade and disseminate systemically to cause disease. Despite this, most vaccines are given parenterally and are unable to induce mucosal immunity. Immunizing directly at the mucosa could solve this problem, however delivering vaccines at these surfaces often doesn’t invoke robust immunity. One way to alleviate this is to use adjuvants that can evoke an immune response. Most adjuvants, like aluminum salts, are unable to induce mucosal immunity and so novel adjuvants must be employed. Outer membrane vesicles (OMVs) from Burkholderia pseudomallei are potent immune mediators and have been shown to have adjuvant capabilities. The goal of this study is to highlight the role of OMVs as a novel adjuvant that can be used in the next generation of mucosal vaccines. To test this, we created an OMV-adjuvanted inactivated whole-cell vaccine against two intracellular pathogens – Salmonella Typhimurium and Francisella holarctica LVS that could be delivered mucosally. An oral vaccine against S. Typhimurium adjuvanted with OMVs showed protection against lethal challenge in addition to evoking antigen specific CD4 T cells, B cells, and anti-Salmonella antibodies. These antibodies induced greater bacterial killing in macrophages. We are currently exploring an OMV-adjuvanted oropharyngeally delivered vaccine against F. holarctica LVS. Immunity against Francisella requires both CD4 and CD8 T cells and we are determining how an OMV-adjuvanted vaccine will influence these immune cell populations. This study represents a novel approach to mucosal vaccines using OMVs as adjuvants. Supported by NIH U01 AI124289 NIH BAA HHSN72201800045C
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Nakkala, Jayachandra Reddy, Yibo Li, Labone Akter, Xinliang Kang i Xinyuan Chen. "Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by MF59 and AS03-like Adjuvants". Vaccines 12, nr 5 (13.05.2024): 531. http://dx.doi.org/10.3390/vaccines12050531.
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MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms.
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Allison, Anthony C. "Adjuvants and Immune Enhancement". International Journal of Technology Assessment in Health Care 10, nr 1 (1994): 107–20. http://dx.doi.org/10.1017/s0266462300014033.
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AbstractAdjuvants increase cell-mediated and humoral immune responses to specific antigens. Used with recombinant viral antigens, they can elicit the production of T lymphocytes that lyse target cells, expressing the antigen in a genetically restricted fashion. Adjuvants can augment the production of interferon-gamma, thereby favoring the production of protective antibody isotopes, such as immuno-globulin G2a in the mouse. Modern adjuvants display the efficacy of Freund's complete adjuvant without its side effects. One such adjuvant is Syntex adjuvant formulation, a synthetic analogue of muramyl dipeptide in a microfluidized squalane/squalene-in-water emulsion. Monophosphoryl lipid A in a similar lipid emulsion is also effective. Immune-stimulating complexes of saponin and antigens elicit potent cell-mediated and humoral responses. A purified saponin component has adjuvant activity with reduced side effects; liposomes also can have adjuvant activity. Administering antigens in adjuvants can overcome low responsiveness in very young and old experimental animals and in those that are genetically low responders. Adjuvants are likely components of a new generation of recombinant and subunit vaccines.
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Cui, Xuemei, Yong Wang, Babar Maqbool, Lijia Yuan, Shanshan He, Cenrong Zhang, Wei Xu i Songhua Hu. "Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant". Vaccines 7, nr 4 (9.10.2019): 143. http://dx.doi.org/10.3390/vaccines7040143.
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The present study evaluated soybean oil (SO) containing vitamin E (VE) and ginseng saponins (GS) (SO-VE-GS) for their adjuvant effect on foot-and-mouth disease (FMD) vaccine. Since mineral oil ISA 206 is a common adjuvant used in the FMD vaccine, it was used as a control adjuvant in this study. VE and GS were found to have a synergistic adjuvant effect. When mice were immunized with the FMD vaccine emulsified in SO with VE and GS, significantly higher serum IgG, IgG1, and IgG2a were found than VE and GS used alone. SO-VE-GS and ISA 206 behaved differently in adjuvant activities. When mice were immunized with the FMD vaccine adjuvanted with SO-VE-GS, significantly higher and earlier production of serum IgG was found than that adjuvanted with ISA 206. Although both adjuvants significantly increased the number of bone marrow plasma cells, a stimulation index of lymphocytes (SI) as well as the production of IL-4 and IL-6, SO-VE-GS promoted significantly higher SI and the ratio of CD4+/CD8+ T cells with production of increased IFN-γ and decreased TGF-β1 as compared with the ISA 206 group. The data suggested that SO-VE-GS activated Th1/Th2 immune responses. Transcriptome analysis of splenocytes showed that differentially expressed genes (DEGs), immune-related gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the SO-VE-GS group. Therefore, the potent adjuvant effect of SO-VE-GS on the FMD vaccine may be attributed to the immune-related gene profile expressed in lymphocytes. Due to its plant origin and due to being much cheaper than imported mineral oil ISA 206, SO-VE-GS deserves further study in relation to vaccines used in food animals.
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Correa, Victor Araujo, Amanda Izeli Portilho i Elizabeth De Gaspari. "Immunological Effects of Dimethyldioctadecylammonium Bromide and Saponin as Adjuvants for Outer Membrane Vesicles from Neisseria meningitidis". Diseases 10, nr 3 (19.07.2022): 46. http://dx.doi.org/10.3390/diseases10030046.
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The meningococcal disease is a global health threat, but is preventable through vaccination. Adjuvants improve meningococcal vaccines and are able to trigger different aspects of the immune response. The present work evaluated the immune response of mice against Neisseria meningitidis outer membrane vesicles (OMV) complexed with the adjuvants aluminium hydroxide (AH), via subcutaneous route; and dimethyldioctadecylammonium bromide (DDA) or Saponin (Sap), via intranasal/subcutaneous routes. ELISA demonstrated that all adjuvants increased IgG titers after the booster dose, remaining elevated for 18 months. Additionally, adjuvants increased the avidity of the antibodies and the bactericidal titer: OMVs alone were bactericidal until 1:4 dilution but, when adjuvanted by Alum, DDA or Sap, it increased to 1/32. DDA and Sap increased all IgG isotypes, while AH improved IgG1 and IgG2a levels. Thus, Sap led to the recognition of more proteins in Immunoblot, followed by DDA and AH. Sap and AH induced higher IL-4 and IL-17 release, respectively. The use of adjuvants improved both cellular and humoral immune response, however, each adjuvant contributed to particular parameters. This demonstrates the importance of studying different adjuvant options and their suitability to stimulate different immune mechanisms, modulating the immune response.
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Khan, Mohammad Suhail, Virginie Jakob, Randhir Singh, Raju S. Rajmani, Sahil Kumar, Céline Lemoine, Harry Kleanthous, Rajesh P. Ringe, Patrice M. Dubois i Raghavan Varadarajan. "Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice". Pharmaceutics 15, nr 12 (12.12.2023): 2759. http://dx.doi.org/10.3390/pharmaceutics15122759.
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Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses. The additional emulsion or liposome-based adjuvants contained a synthetic TLR-4 ligand and/or the saponin QS-21. Trimerization enhanced immunogenicity, with significant antibody titers detectable after a single immunization. Saponin-containing adjuvants elicited enhanced immunogenicity relative to both emulsion and aluminum hydroxide adjuvanted formulations lacking these immunostimulants. Trimeric RBD formulated with liposomal based adjuvant containing both TLR-4 ligand and saponin elicited a strongly Th1 biased response, with ~10-fold higher neutralization titers than the corresponding aluminum hydroxide adjuvanted formulation. The SARS-CoV-2 virus is now endemic in humans, and it is likely that periodic updating of vaccine formulations in response to viral evolution will continue to be required to protect vulnerable individuals. In this context, it is desirable to have efficacious, thermostable vaccine formulations to facilitate widespread vaccine coverage, including in low- and middle-income countries, where global access rights to clinically de-risked adjuvants will be important moving forward.
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Gaskin, R. E., D. B. Horgan, R. M. Van_Leeuwen i D. W. Manktelow. "Adjuvant effects on the retention and uptake of spirotetramat insecticide sprays on kiwifruit". New Zealand Plant Protection 63 (1.08.2010): 60–65. http://dx.doi.org/10.30843/nzpp.2010.63.6569.
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Spirotetramat (Movento) is a systemic insecticide that can control scale insects on kiwifruit It must be tankmixed with a spray adjuvant to maximise leaf uptake This study investigated how two adjuvants a penetrating oil and a superspreader affected spray retention and uptake of spirotetramat into kiwifruit leaves from dilute and concentrated spray mixes Spray retention and distribution of airblastapplied high volume dilute sprays containing the oil adjuvant were good but retention was reduced when sprays were concentrated Concentrated sprays containing the superspreader adjuvant were retained and distributed similarly to the dilute sprays containing oil adjuvant Spirotetramat uptake into foliage was generally low but was greater with the oil penetrant than with the superspreader Concentrating sprays and increasing adjuvant concentrations could increase insecticide uptake as could combining the two adjuvants together in a spray The potential of the adjuvants to maximise spirotetramat efficacy in concentrate sprays and to reduce residues at harvest is discussed
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Kim, Jeremiah Y., Matthew G. Rosenberger, Nakisha S. Rutledge i Aaron P. Esser-Kahn. "Next-Generation Adjuvants: Applying Engineering Methods to Create and Evaluate Novel Immunological Responses". Pharmaceutics 15, nr 6 (8.06.2023): 1687. http://dx.doi.org/10.3390/pharmaceutics15061687.
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Adjuvants are a critical component of vaccines. Adjuvants typically target receptors that activate innate immune signaling pathways. Historically, adjuvant development has been laborious and slow, but has begun to accelerate over the past decade. Current adjuvant development consists of screening for an activating molecule, formulating lead molecules with an antigen, and testing this combination in an animal model. There are very few adjuvants approved for use in vaccines, however, as new candidates often fail due to poor clinical efficacy, intolerable side effects, or formulation limitations. Here, we consider new approaches using tools from engineering to improve next-generation adjuvant discovery and development. These approaches will create new immunological outcomes that will be evaluated with novel diagnostic tools. Potential improved immunological outcomes include reduced vaccine reactogenicity, tunable adaptive responses, and enhanced adjuvant delivery. Evaluations of these outcomes can leverage computational approaches to interpret “big data” obtained from experimentation. Applying engineering concepts and solutions will provide alternative perspectives, further accelerating the field of adjuvant discovery.
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Fan, Jingyi, Shengbin Jin, Lachlan Gilmartin, Istvan Toth, Waleed M. Hussein i Rachel J. Stephenson. "Advances in Infectious Disease Vaccine Adjuvants". Vaccines 10, nr 7 (13.07.2022): 1120. http://dx.doi.org/10.3390/vaccines10071120.
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Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases. Immune stimulants (or adjuvants) are an indispensable factor in vaccine development, especially for inactivated and subunit-based vaccines due to their decreased immunogenicity compared to whole pathogen vaccines. Adjuvants are widely diverse in structure; however, their overall function in vaccine constructs is the same: to enhance and/or prolong an immunological response. The potential for adverse effects as a result of adjuvant use, though, must be acknowledged and carefully managed. Understanding the specific mechanisms of adjuvant efficacy and safety is a key prerequisite for adjuvant use in vaccination. Therefore, rigorous pre-clinical and clinical research into adjuvant development is essential. Overall, the incorporation of adjuvants allows for greater opportunities in advancing vaccine development and the importance of immune stimulants drives the emergence of novel and more effective adjuvants. This article highlights recent advances in vaccine adjuvant development and provides detailed data from pre-clinical and clinical studies specific to infectious diseases. Future perspectives into vaccine adjuvant development are also highlighted.
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Pujisiswanto, Hidayat, Yayuk Nurmiaty, Nanik Sriyani i Annisa Efrima. "Pengaruh Ekstrak Buah Lerak (Sapindus rarak) dan Beberapa Adjuvan terhadap Perkecambahan Gulma Fimbristylis miliacea". JURNAL AGROTROPIKA 20, nr 2 (3.10.2021): 104. http://dx.doi.org/10.23960/ja.v20i2.5205.
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Adjuvant is an ingredient added in a formulation to increase the effectiveness of lerak fruit in inhibiting weeds. This study aims to determine the type of adjuvant in lerak fruit extract that can increase the inhibition of germination of Fimbristylis miliacea and to determine the type of adjuvant in lerak fruit extract that is most effective in inhibiting the germination of F. miliacea. The research was conducted from December 2019 to March 2020 in the Weed Laboratory, Faculty of Agriculture, University of Lampung. This study used a Completely Randomized Design (CRD) to determine the type of adjuvant given to lerak fruit extract on F. miliacea germination with 4 replications. The treatments consisted of lerak fruit extract, lerak fruit extract + VCO adjuvant, lerak fruit extract + KAO adjuvant, lerak fruit extract + Polysorbate 80 adjuvant, and control. The Bartlett test was used to test the homogeneity of variance, if the assumptions of the analysis of variance were met, then the mean value of the treatment was continued with the Least Significant Difference (LSD) test at the 5% level. The results showed that adjuvants and without adjuvants added to lerak fruit extract at a concentration of 50% (500 g/l) were able to suppress the percentage of germination and the speed of germination of Fimbristylis miliace seeds.Keywords: adjuvants, lerak fruit extract, Fimbristylis miliacea, weed
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Harberts, Erin M., David J. Varisco, James K. Fields, Jerilyn R. Izac, Francesca M. Gardner, Eric J. Sundberg, Greg A. Snyder i Robert K. Ernst. "Lipid A mimetics BECC438 and BECC470 potentiate durable and balanced immune responses using an ovalbumin murine vaccine model." Journal of Immunology 206, nr 1_Supplement (1.05.2021): 59.02. http://dx.doi.org/10.4049/jimmunol.206.supp.59.02.
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Abstract The need for effective infectious disease vaccines has become an inescapable topic over the past year. Continued development of next-generation vaccines that provide robust protective immunity is imperative. Such vaccines will likely include an adjuvant that avoids excessive adverse reactions and allows for dose and antigen sparing. Bacterial lipid A mimetics BECC438 and BECC470 have recently emerged as lead adjuvant candidates across several experimental models of infectious disease including Yersinia pestis (plague), human papilloma virus (HPV), and influenza-A (flu). To further define BECC438 and BECC470 as immuno-adjuvants, even without antigen from an infectious pathogen, studies presented here use ovalbumin (Ova) as a model antigen in a murine prime-boost vaccine model. Higher magnitude and more balanced production of antibody isotypes IgG1 and IgG2 are observed when BECC adjuvants are compared to classic adjuvants alum and PHAD. This optimal antibody response is durable and maintained for at least 12 weeks post-vaccination. Initial experiments use C57BL6 mice and are expanded to include BALBc and CD-1 (outbred) mice. Observed immune metrics maintained similar trends across male and females, and genetic backgrounds tested. Biacore immunogenicity analysis of C57BL6 serum found an increased half-life of Ova-specific antibodies in BECC438-adjuvanted animals potentially indicative of a higher antigen binding affinity. Toxicity studies conducted in New Zealand White rabbits report that BECC438 was well tolerated with no significant reactogenicity after 50μg and 100μg intra-muscular adjuvant injection. These studies provide continued evidence supporting development of BECC adjuvants in vaccines for human use.
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Raaijmakers, Tonke K., Renske J. E. van den Bijgaart, Martijn H. den Brok, Melissa Wassink, Annemarie de Graaf, Jori A. Wagenaars, Stefan Nierkens, Marleen Ansems, Gert Jan Scheffer i Gosse J. Adema. "Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes". Journal for ImmunoTherapy of Cancer 8, nr 1 (maj 2020): e000649. http://dx.doi.org/10.1136/jitc-2020-000649.
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BackgroundTumor ablation techniques, like cryoablation, are successfully used in the clinic to treat tumors. The tumor debris remaining in situ after ablation is a major antigen depot, including neoantigens, which are presented by dendritic cells (DCs) in the draining lymph nodes to induce tumor-specific CD8+T cells. We have previously shown that co-administration of adjuvants is essential to evoke strong in vivo antitumor immunity and the induction of long-term memory. However, which adjuvants most effectively combine with in situ tumor ablation remains unclear.Methods and resultsHere, we show that simultaneous administration of cytidyl guanosyl (CpG) with saponin-based adjuvants following cryoablation affects multifunctional T-cell numbers and interleukin (IL)-1 induced polymorphonuclear neutrophil recruitment in the tumor draining lymph nodes, relative to either adjuvant alone. The combination of CpG and saponin-based adjuvants induces potent DC maturation (mainly CpG-mediated), antigen cross-presentation (mainly saponin-based adjuvant mediated), while excretion of IL-1β by DCs in vitro depends on the presence of both adjuvants. Most strikingly, CpG/saponin-based adjuvant exposed DCs potentiate antigen-specific T-cell proliferation resulting in multipotent T cells with increased capacity to produce interferon (IFN)γ, IL-2 and tumor necrosis factor-α in vitro. Also in vivo the CpG/saponin-based adjuvant combination plus cryoablation increased the numbers of tumor-specific CD8+T cells showing enhanced IFNγ production as compared with single adjuvant treatments.ConclusionsCollectively, these data indicate that co-injection of CpG with saponin-based adjuvants after cryoablation induces an increased amount of tumor-specific multifunctional T cells. The combination of saponin-based adjuvants with toll-like receptor 9 adjuvant CpG in a cryoablative setting therefore represents a promising in situ vaccination strategy.
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Starke, Robert J., Karen A. Renner, Donald Penner i Frank C. Roggenbuck. "Influence of Adjuvants and Desmedipham plus Phenmedipham on Velvetleaf (Abutilon theophrasti) and Sugarbeet Response to Triflusulfuron". Weed Science 44, nr 3 (wrzesień 1996): 489–95. http://dx.doi.org/10.1017/s0043174500094236.
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Greenhouse studies determined the influence of 14 adjuvants and desmedipham plus phenmedipham on velvetleaf control and sugarbeet injury by triflusulfuron. A second study determined if six adjuvants, or desmedipham plus phenmedipham, influenced14C-triflusulfuron absorption by cotyledon or first true leaves of velvetleaf. Triflusulfuron applied twice at 4.4 g ai ha−1(split application), alone or in combination with any adjuvant, did not reduce sugarbeet dry weight. Desmedipham plus phenmedipham applied twice at 370 g ai ha−1(split application) reduced sugarbeet dry weight 3%. The addition of an adjuvant to desmedipham plus phenmedipham reduced sugarbeet dry weight 21 to 66% depending on the adjuvant. Sugarbeet injury was not greater when triflusulfuron was applied with any adjuvant (except urea ammonium nitrate (UAN)) plus desmedipham plus phenmedipham compared to desmedipham plus phenmedipham plus the respective adjuvant alone. Velvetleaf was most easily controlled in the cotyledon stage of growth. Velvetleaf control by triflusulfuron increased from 0 (no adjuvant) to 80% by the addition of Scoil or Sylgard 309 plus UAN. Cotyledonary leaves of velvetleaf absorbed 28% more14C-triflusulfuron than first true leaves. Adjuvant increased14C-triflusulfuron absorption by cotyledonary leaves from 15% (no adjuvant) to 48 to 90%. Desmedipham plus phenmedipham decreased velvetleaf control by triflusulfuron plus X-77 or X77 plus UAN compared to triflusulfuron plus the adjuvant alone. Velvetleaf control by triflusulfuron plus other adjuvants was not reduced by desmedipham plus phenmedipham. Absorption of14C-triflusulfuron by cotyledonary and first true leaf velvetleaf decreased when desmedipham plus phenmedipham was added to triflusulfuron plus Dash, Dash plus UAN, X-77, X-77 plus UAN, and Sylgard 309 plus UAN.
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Editorial Staff. "Boosting Adjuvant Activity". Molecular Medicine Communications 1, nr 1 (22.12.2021): 07–09. http://dx.doi.org/10.55627/mmc.001.01.0064.
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Despite a limited stock approved for clinical application, adjuvants still remain a vital component of vaccines due to their ability to enhance responses against antigens bearing poor immunogenicity. Silva and his colleagues synthesized a novel adjuvant consisting of saponin-bearing detergent-like properties and a monophosphoryl lipid A (MPLA) that serves as a Toll-like receptor 4 agonist, both encapsulated in nanoparticle structures. The novel adjuvant formulation invoked increased antibody and germinal center responses as compared to an assortment of already available adjuvants, in both mice and rhesus macaques post-inoculation of an HIV antigen that had poor immunogenic characteristics. In a mast cell-dependent fashion, increased lymphatic flow was observed with saponin–MPLA nanoparticles. Furthermore, lymph nodes also had an enhanced antigen load, indicating the mechanisms by which saponin consisting of adjuvants improves humoral immune responses. Sci Immunol. 2021 Dec 3;6(66):eabf1152.
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Barbateskovic, Marija, Sarah Louise Klingenberg, Sara Russo Krauss, Dezhao Kong, Zhangtong Wu, Sesilje B. Petersen, Mette Kenfelt i Christian Gluud. "Concentrations, Number of Doses, and Formulations of Aluminium Adjuvants in Vaccines: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials". Vaccines 11, nr 12 (27.11.2023): 1763. http://dx.doi.org/10.3390/vaccines11121763.
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Aluminium adjuvants are commonly used in vaccines to boost the effects of vaccination. Here, we assessed the benefits and harms of different aluminium adjuvants vs. other aluminium adjuvants or vs. the same aluminium adjuvant at other concentrations, administered a different number of doses, or at different particle sizes used in vaccines or vaccine excipients. We conducted a systematic review with meta-analysis and Trial Sequential Analysis to assess the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We obtained data from major medical databases until 20 January 2023 and included 10 randomized clinical trials of healthy volunteers. The comparisons assessed higher vs. lower aluminium adjuvant concentrations; higher vs. lower number of doses of aluminium adjuvant; and aluminium phosphate adjuvant vs. aluminium hydroxide adjuvant. For all three comparisons, meta-analyses showed no evidence of a difference on all-cause mortality, serious adverse events, and adverse events considered non-serious. The certainty of evidence was low to very low. None of the included trials reported on quality of life or proportion of participants who developed the disease being vaccinated against. The benefits and harms of different types of aluminium adjuvants, different aluminium concentrations, different number of doses, or different particle sizes, therefore, remain uncertain.
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Phelps, Kathleen, Mei Xia, Valerio Rasi, Christopher Fox, Nikolai Petrovsky, Darrick Carter i Daniel Hoft. "Identification of adjuvants for γδ T cells in response to a novel M. tuberculosis vaccine antigen". Journal of Immunology 208, nr 1_Supplement (1.05.2022): 181.10. http://dx.doi.org/10.4049/jimmunol.208.supp.181.10.
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Abstract γδ T cells are ideal effector cells against infectious diseases and cancer. They reside in blood, lymphoid organs, and mucosa, readily available for host defense. γδ T cells develop memory responses independent of MHC presentation. They perform immune functions such as cytolysis, cytokine production, antigen presentation, dendritic cell maturation, and promotion of B cell and T cell responses. Our lab reported that γδ T cells responsive to M. tuberculosis-specific 6-O-methylglucose-containing lipopolysaccharides (mGLP) inhibit intracellular mycobacterial growth. Preliminary data from NHP studies indicate that vaccination with mGLP and IL-2 greatly reduces Mtb burden post-challenge. IL-2 is not translatable for adjuvant use in humans. Therefore, novel adjuvants for γδ T cells are needed to develop optimal vaccine strategies. We are investigating adjuvant candidates to determine their ability to induce optimal activation and expansion of γδ T cells with mGLP or the phosphoantigen HMBPP. To screen adjuvants, PBMCs are incubated with antigen and adjuvant for 7 days, then analyzed for expansion of γδ T cells. Initially few adjuvants promoted γδ T cell expansion in response to HMBPP and none to mGLP. When matured monocyte-derived DCs were added, multiple adjuvants promoted γδ T cell expansion in response to HMBPP and mGLP stimulation without IL-2. We will determine mechanisms involved in novel adjuvant activity, whether adjuvant and mGLP-expanded γδ T cells inhibit intracellular mycobacterial growth, identify cytokines involved in candidate adjuvant effects, characterize cell surface markers upregulated on DC and γδ T cells, and test the best candidate adjuvant(s) with mGLP in NHP trials. Supported by Gama Delta R01 AI048391
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Nisavic, Jakov, Natasa Kustudic-Nikoletic, Nenad Milic i Andrea Zoric. "Examination of the influence of different adjuvants on the immunogenicity of vaccines against parainfluenza 3 virus in cattle". Veterinarski glasnik 70, nr 3-4 (2016): 99–110. http://dx.doi.org/10.2298/vetgl1604099n.
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The objective of our research was to examine the influence of different adjuvants on immunogenicity of vaccine against parainfluenza 3 virus in cattle. In the research there was used the commercial vaccine Respi-ol against PI3 virus in cattle, produced by VZS from Subotica as well as the experimental vaccine against the same virus prepared with completed adjuvant Emulsigen. The research was performed on two experimental groups of 12 calves each. The animals were immunized twice, in the interval of 21 days. The third group of 6 calves was a control. The results of the research showed that a smaller amount of adjuvent Emulsigen per vaccine dose provided a satisfactory height of titre of virus neu?tralizing antibodies in the blood serum samples of vaccinated calves in regard to prescribed greater amount of standard oil adjuvant contained in commercial Respi-ol vaccine.
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Lohsen, Mark, Xiuping Liu, Deana Toussi, Paola Massari i Lee Wetzler. "The Role of MyD88 in the Adjuvant Activity of Neisseria meningitidis PorB (53.5)". Journal of Immunology 188, nr 1_Supplement (1.05.2012): 53.5. http://dx.doi.org/10.4049/jimmunol.188.supp.53.5.
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Abstract Adjuvants enhance the response to poorly immunogenic antigens in vaccines. Our laboratory has shown by ELISA that Neisseria meningitidis outer membrane protein PorB acts as an adjuvant by eliciting a greater serum concentration of antigen-specific IgG when compared to immunization with antigen alone, with Ovalbumin as the antigen. PorB is a TLR2 ligand and signals through the adaptor protein MyD88. We compared the adjuvant effect of PorB to other adjuvants (Alum, MPL & CpG) in WT & MyD88 KO mice. PorB adjuvant activity was ablated in MyD88 KO mice and consistent with previous investigations: MPL & CpG adjuvant activity was also MyD88-dependent while Alum acted independently of MyD88. In addition, we previously observed PorB had residual adjuvant activity in TLR2 KO mice. One hypothesis was that PorB could stimulate the Nalp3 inflammasome and induce IL-1β production without a second signal e.g. ATP. Therefore, bone marrow-derived macrophages were stimulated with PorB ± ATP. The IL-1β production was analyzed by ELISA and compared to IL-1β production from stimulation with other TLR ligands. We found that PorB required ATP in order to sufficiently produce IL-1β, disproving our hypothesis. Overall, our results show an importance for MyD88 in both the adjuvant pathway of PorB & other TLR ligand-based adjuvants. One future direction for this work is MyD88 deletion in an antigen-presenting cell-specific manner to examine the role of each cell type in the adjuvant activity of PorB.
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McMullan, Patrick M., i Desiree L. Czerkawski. "The effect of adjuvant type and rate on the efficacy of sethoxydim and RO-17-3664". Canadian Journal of Plant Science 71, nr 3 (1.07.1991): 881–84. http://dx.doi.org/10.4141/cjps91-128.
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Greenhouse experiments were conducted to determine the effectiveness of various adjuvants and herbicide-adjuvant mixing method on sethoxydim and RO-17-3664 [[{isopropylideneamino) oxy] ethyl-D-(+)-2- [p-{(6-chloro-2-quinooxalinyl)-oxy]phenoxy] propionate] efficacy on wild oats. Mixing the herbicide with adjuvant before dilution did not decrease herbicide efficacy compared to regular herbicide-adjuvant dilution. The emulsifier surfactant concentration in the adjuvant appeared to be related to the adjuvant volume required. The emulsifier surfactant alone enhanced RO-17-3664 activity. Key words: oat (wild), Avena fatua, sethoxydim, RO-17-3664, surfactant, emulsifier
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Miller, Shannon M., Christine Robinson, Margaret Whitacre, Cassandra Buhl, Bethany Crouse, Marco Pravetoni i Jay T. Evans. "A novel TLR adjuvant increases the efficacy of vaccines against fentanyl-induced toxicity and overdose". Journal of Immunology 204, nr 1_Supplement (1.05.2020): 91.25. http://dx.doi.org/10.4049/jimmunol.204.supp.91.25.
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Abstract The widespread illicit use of fentanyl and its analogs is associated with the increased incidence of fatal drug overdoses in the United States in recent years. Pre-clinical studies with vaccines targeting opioids show selectivity and efficacy but clinical data suggests vaccine efficacy against drugs of abuse may be limited by individual variability and a requirement for high and sustained antibody levels. New strategies are needed to enhance vaccine efficacy and increase the quantity and quality of the anti-drug antibody response. We investigated the ability of novel synthetic TLR adjuvants to increase anti-fentanyl antibody titers and protect from fentanyl challenge in mice. Fentanyl-based haptens were conjugated to CRM and combined with alum, novel synthetic TLR adjuvants, or combinations thereof. The most promising TLR adjuvants and combination adjuvants increased anti-fentanyl hapten total IgG, IgG1, and IgG2a antibody concentrations. Splenocyte restimulation with CRM protein showed adjuvant combinations significantly increased secretion of Th1-type cytokines compared to antigen only or single adjuvants alone. Likewise, in a fentanyl challenge model, combination adjuvanted vaccines increased protection from respiratory depression compared to mice vaccinated with antigen alone or single adjuvant controls. These data demonstrate that TLR adjuvants improve the anti-fentanyl adaptive immune response and increase protection against fentanyl challenge in mice, and may enhance vaccine-induced protection against fentanyl overdose in humans.
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Dalençon, François. "Modern Vaccine Adjuvant/Formulation—Session 9: Adjuvants". Human Vaccines & Immunotherapeutics 9, nr 9 (19.09.2013): 2013–14. http://dx.doi.org/10.4161/hv.26074.
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Sherrick, Stewart L., Harvey A. Holt i F. Dan Hess. "Effects of Adjuvants and Environment During Plant Development on Glyphosate Absorption and Translocation in Field Bindweed (Convolvulus arvensis)". Weed Science 34, nr 6 (listopad 1986): 811–16. http://dx.doi.org/10.1017/s004317450006793x.
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Absorption and translocation of glyphosate [N-(phosphonomethyl)glycine] with and without adjuvants were examined in field bindweed (Convolvulus arvensisL. # CONAR) to develop an understanding of the influence of selected adjuvants and environment before application on glyphosate activity. Light intensity and humidity during plant development resulted in differences in14C-glyphosate absorption. When applied in water or with an oxysorbic (20 POE) (polyoxyethylene sorbitan monolaurate) adjuvant, an average of 9% of the glyphosate was absorbed in plants grown in high light intensity, low humidity (HLLH) before treatment, compared to an average of 21% in plants grown in low light, high humidity (LLHH) before treatment, respectively. Amounts of epicuticular wax on HLLH field bindweed were almost three times as great as on LLHH leaves and may explain absorption differences. No differences in glyphosate absorption were observed between glyphosate applied with oxysorbic or no adjuvant even though the oxysorbic adjuvant effectively reduces surface tension. Absorption was increased two- to threefold with a polyethoxylated tallow amine adjuvant (MON 0818) compared to no adjuvant. Unlike absorption without adjuvant or with oxysorbic adjuvant, there were few absorption differences in plants grown in different environments before application. Absorption continued for 24 to 36 h after application regardless of adjuvant. Reductions in MON 0818 concentration and subsequent necrosis resulted in increased movement of radioactivity away from the site of application.
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Yang, Ya-Wun, i Chih-Feng Chang. "Induction of differentiation of hematopoietic cells by the vaccine adjuvants (75.10)". Journal of Immunology 188, nr 1_Supplement (1.05.2012): 75.10. http://dx.doi.org/10.4049/jimmunol.188.supp.75.10.
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Abstract Vaccine adjuvants have been used to enhance the immune responses against the co-administered antigens. The mechanisms of action by the adjuvants however remain poorly understood. We attempt to investigate in this study the effect of vaccine adjuvants on differentiation of the hematopoietic system. C57BL/6J mice were vaccinated with ovalbumin (OVA) in L121-adjuvant, an emulsion adjuvant consists of Pluronic L121 that previously shown to stimulate cytotoxic lymphocyte (CTL) effect. Cells were isolated from bone marrow and thymus after vaccination, followed by flow cytometric analysis. Our data showed that treatment of animals with L121-adjuvant skewed the differentiation of hematopoietic cells, resulting in a significant increase of the CD11b+ population at the expense of lineage (lin)+ cells, attributing mainly to a dramatic reduction of the B220+ population. A considerable increase of Lin-/Sca1+/c-Kit+ (LSK) hematopoietic stem/progenitor cells was observed in the bone marrow of immunized mice, suggesting an induction of enhanced cell expansion by the vaccine adjuvant. Treatment of animals with L121-adjuvant also affects the differentiation of cells in the thymus with a decrease of the CD4+/CD8+ double-positive (DP) cells, and a concurrent increase of the CD4+ and CD8+ single positive (SP) populations. These experimental results suggested the differentiation effect of vaccine adjuvants on the hematopoietic system, accounting for the enhanced immunity after immunization.
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Kwiatkowski, Cezary A., Marian Wesołowski, Elżbieta Harasim, Dorota Gawęda, i Magda Drabowicz. "The effect of reduced rates of crop protection agents and adjuvants on productivity, weed infestation and health of spring barley (Hordeum sativum L.)". Acta Agrobotanica 66, nr 3 (2013): 103–12. http://dx.doi.org/10.5586/aa.2013.044.
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A field experiment on the cultivation of spring barley was carried out in the period 2009–2011 at the Experimental Farm in Czesławice (central Lublin region) on grey-brown podzolic soil derived from loess (soil quality class II). The study included 3 rates of herbicides, growth retardant and fungicides (100%, 75% and 50%) as well as different types of adjuvant (oil, surface-active, mineral). Plots without adjuvant were the control treatment. A hypothesis was made that the reduction in rates of crop protection agents by 25–50%, with the simultaneous addition of adjuvants, would allow spring barley productivity to be maintained at a level similar to that obtained under the conditions when recommended rates are applied without adjuvant. It was also assumed that particular types of adjuvant would show different interactions with specific groups of crop protection agents. It has been proved that a rational reduction in rates of crop protection agents is up to a limit of 25%, especially when an adjuvant is added to such reduced rates. This allows spring barley productivity to be maintained at the level obtained after the application of full rates (without adjuvant). But a further reduction in rates of crop protection agents by 50%, in spite of the interaction of adjuvants, results in a significant deterioration of all spring barley yield components, since such conditions lead to increased occurrence of agricultural pests (weeds, fungal diseases) as well as increased crop lodging. Among the group of adjuvants tested in the present experiment, the oil adjuvant Atpolan 80 EC showed the best interaction with crop protection agents used.
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He, Qing, Alaina R. Mitchell, Stacy L. Johnson, Claus Wagner-Bartak, Tulin Morcol i Steve J. D. Bell. "Calcium Phosphate Nanoparticle Adjuvant". Clinical Diagnostic Laboratory Immunology 7, nr 6 (1.11.2000): 899–903. http://dx.doi.org/10.1128/cdli.7.6.899-903.2000.
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ABSTRACT Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.
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Pogostin, Brett H., i Kevin J. McHugh. "Novel Vaccine Adjuvants as Key Tools for Improving Pandemic Preparedness". Bioengineering 8, nr 11 (24.10.2021): 155. http://dx.doi.org/10.3390/bioengineering8110155.
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Future infectious disease outbreaks are inevitable; therefore, it is critical that we maximize our readiness for these events by preparing effective public health policies and healthcare innovations. Although we do not know the nature of future pathogens, antigen-agnostic platforms have the potential to be broadly useful in the rapid response to an emerging infection—particularly in the case of vaccines. During the current COVID-19 pandemic, recent advances in mRNA engineering have proven paramount in the rapid design and production of effective vaccines. Comparatively, however, the development of new adjuvants capable of enhancing vaccine efficacy has been lagging. Despite massive improvements in our understanding of immunology, fewer than ten adjuvants have been approved for human use in the century since the discovery of the first adjuvant. Modern adjuvants can improve vaccines against future pathogens by reducing cost, improving antigen immunogenicity, and increasing antigen stability. In this perspective, we survey the current state of adjuvant use, highlight potentially impactful preclinical adjuvants, and propose new measures to accelerate adjuvant safety testing and technology sharing to enable the use of “off-the-shelf” adjuvant platforms for rapid vaccine testing and deployment in the face of future pandemics.
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JANJAM, SRI SUSHMA SANTHI, Yajun Geng, Zhaoqi yan, Soo Min Shin, Kanak Joshi, Anjali Jacob Panicker, Archana shankar i in. "Complete tolerogenic response adjuvant stimulates Treg response to immunization". Journal of Immunology 210, nr 1_Supplement (1.05.2023): 158.08. http://dx.doi.org/10.4049/jimmunol.210.supp.158.08.
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Abstract We identified the lowest composition necessary to generate a vaccination adjuvant that promotes a Treg response following immunization in mice and named it “complete tolerogenic adjuvant.” This novel adjuvant may allow us to utilize the well-established “antigen plus adjuvant” method of vaccination to induce Treg cell-mediated antigen-specific immunosuppression. The minimal composition is dexamethasone, rapamycin, and monophosphoryl lipid A with the following mass ratios: 8:20:3. We have demonstrated why immunosuppressive and immunogenic substances are both required for the formation of genuine adjuvants for Treg cells by dissecting the roles of each of these components during vaccination. Currently, research is ongoing in our group to begin to assess the usefulness of this adjuvant for antigen immunization in murine models of human autoimmune/inflammatory diseases. Specifically, we are evaluating the tolerogenic efficacy of this adjuvant for vaccination regimen targeting the apolipoprotein B antigen, using the ApoE−/− mouse model of atherosclerosis. These studies are expected to help drive the development of further, perhaps more effective, complete tolerogenic adjuvants that could be used to create a plethora of new, novel vaccines for treating immunological illnesses. Master program and NIH grant
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Martiñón, Susana, Angel Cisneros, Sergio Villicaña, Ricardo Hernández-Miramontes, Edgar Mixcoha i Psyché Calderón-Vargas. "Chemical and Immunological Characteristics of Aluminum-Based, Oil-Water Emulsion, and Bacterial-Origin Adjuvants". Journal of Immunology Research 2019 (8.05.2019): 1–9. http://dx.doi.org/10.1155/2019/3974127.
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Adjuvants are a diverse family of substances whose main objective is to increase the strength, quality, and duration of the immune response caused by vaccines. The most commonly used adjuvants are aluminum-based, oil-water emulsion, and bacterial-origin adjuvants. In this paper, we will discuss how the election of adjuvants is important for the adjuvant-mediated induction of immunity for different types of vaccines. Aluminum-based adjuvants are the most commonly used, the safest, and have the best efficacy, due to the triggering of a strong humoral response, albeit generating a weak induction of cell-mediated immune response. Freund’s adjuvant is the most widely used oil-water emulsion adjuvant in animal trials; it stimulates inflammation and causes aggregation and precipitation of soluble protein antigens that facilitate the uptake by antigen-presenting cells (APCs). Adjuvants of bacterial origin, such as flagellin,E. colimembranes, and monophosphoryl lipid A (MLA), are known to potentiate immune responses, but their safety and risks are the main concern of their clinical use. This minireview summarizes the mechanisms that classic and novel adjuvants produce to stimulate immune responses.