Academic literature on the topic 'HIV vaccine; adjuvants'
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Journal articles on the topic "HIV vaccine; adjuvants"
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Berendam, Stella J., Papa K. Morgan-Asiedu, Riley J. Mangan, Shuk Hang Li, Holly Heimsath, Kan Luo, Alan D. Curtis, et al. "Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques." PLOS ONE 16, no. 12 (December 31, 2021): e0256885. http://dx.doi.org/10.1371/journal.pone.0256885.
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Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06–1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.
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Moser, B. A., R. C. Steinhardt, Y. Escalante-Buendia, D. A. Boltz, K. M. Barker, B. J. Cassaidy, M. G. Rosenberger, S. Yoo, B. G. McGonnigal, and A. P. Esser-Kahn. "Increased vaccine tolerability and protection via NF-κB modulation." Science Advances 6, no. 37 (September 2020): eaaz8700. http://dx.doi.org/10.1126/sciadv.aaz8700.
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Improving adjuvant responses is a promising pathway to develop vaccines against some pathogens (e.g., HIV or dengue). One challenge in adjuvant development is modulating the inflammatory response, which can cause excess side effects, while maintaining immune activation and protection. No approved adjuvants yet have the capability to independently modulate inflammation and protection. Here, we demonstrate a method to limit inflammation while retaining and often increasing the protective responses. To accomplish this goal, we combined a partial selective nuclear factor kappa B (NF-kB) inhibitor with several current adjuvants. The resulting vaccines reduce systemic inflammation and boost protective responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method was tested across a broad range of adjuvants and antigens. We anticipate these studies will lead to an alternative approach to vaccine formulation design that may prove broadly applicable to a wide range of adjuvants and vaccines.
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Kozlowski, Pamela A., and Anna Aldovini. "Mucosal Vaccine Approaches for Prevention of HIV and SIV Transmission." Current Immunology Reviews 15, no. 1 (April 12, 2019): 102–22. http://dx.doi.org/10.2174/1573395514666180605092054.
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Optimal protective immunity to HIV will likely require that plasma cells, memory B cells and memory T cells be stationed in mucosal tissues at portals of viral entry. Mucosal vaccine administration is more effective than parenteral vaccine delivery for this purpose. The challenge has been to achieve efficient vaccine uptake at mucosal surfaces, and to identify safe and effective adjuvants, especially for mucosally administered HIV envelope protein immunogens. Here, we discuss strategies used to deliver potential HIV vaccine candidates in the intestine, respiratory tract, and male and female genital tract of humans and nonhuman primates. We also review mucosal adjuvants, including Toll-like receptor agonists, which may adjuvant both mucosal humoral and cellular immune responses to HIV protein immunogens.
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Louis, Lumena, Megan C. Wise, Hyeree Choi, Daniel O. Villarreal, Kar Muthumani, and David B. Weiner. "Designed DNA-Encoded IL-36 Gamma Acts as a Potent Molecular Adjuvant Enhancing Zika Synthetic DNA Vaccine-Induced Immunity and Protection in a Lethal Challenge Model." Vaccines 7, no. 2 (May 22, 2019): 42. http://dx.doi.org/10.3390/vaccines7020042.
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Identification of novel molecular adjuvants which can boost and enhance vaccine-mediated immunity and provide dose-sparing potential against complex infectious diseases and for immunotherapy in cancer is likely to play a critical role in the next generation of vaccines. Given the number of challenging targets for which no or only partial vaccine options exist, adjuvants that can address some of these concerns are in high demand. Here, we report that a designed truncated Interleukin-36 gamma (IL-36 gamma) encoded plasmid can act as a potent adjuvant for several DNA-encoded vaccine targets including human immunodeficiency virus (HIV), influenza, and Zika in immunization models. We further show that the truncated IL-36 gamma (opt-36γt) plasmid provides improved dose sparing as it boosts immunity to a suboptimal dose of a Zika DNA vaccine, resulting in potent protection against a lethal Zika challenge.
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Ozorowski, Gabriel, Albert Cupo, Michael Golabek, Michelle LoPiccolo, Thomas A. Ketas, Matt Cavallary, Christopher A. Cottrell, P. J. Klasse, Andrew B. Ward, and John P. Moore. "Effects of Adjuvants on HIV-1 Envelope Glycoprotein SOSIP TrimersIn Vitro." Journal of Virology 92, no. 13 (April 18, 2018): e00381-18. http://dx.doi.org/10.1128/jvi.00381-18.
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ABSTRACTNative-like, soluble, recombinant SOSIP trimers of various designs and based on severalenvgenes of human immunodeficiency virus type 1 (HIV-1) are being tested as immunogens in different animal models. These experiments almost always involve coformulating the trimers with an adjuvant to boost the magnitude of the immune responses. One factor relevant to the choice of an adjuvant is that it should not physically damage the immunogen or impede its ability to present relevant epitopes. As examples, an adjuvant formulation that includes harsh detergents could disrupt the structural integrity of a trimer, and any charged compounds in the formulation could bind to countercharged regions of the trimer and physically occlude nearby epitopes. While a few adjuvants have been tested for their potential effects on SOSIP trimersin vitro, there has been no systematic study. Here, we have assessed how nine different adjuvants of various compositions affect SOSIP trimers of the BG505 and B41 genotypes. We used negative-stain electron microscopy, thermal denaturation, and gel electrophoresis to evaluate effects on trimer integrity and immunoassays to measure effects on the presentation of various epitopes. We conclude that most of the tested adjuvants are benign from these perspectives, but some raise grounds for concern. An acidified alum formulation is highly disruptive to trimer integrity, and a DNA-based polyanionic CpG oligodeoxynucleotide adjuvant binds to trimers and occludes the trimer apex epitope for the PGT145 neutralizing antibody. The methods described here should be generalizable to protein subunit vaccines targeting various pathogens.IMPORTANCEAdjuvant formulations increase the magnitude of immune responses to vaccine antigens. They are critically important for formulation of HIV-1 envelope glycoprotein (Env) vaccines intended to induce antibody production, as Env proteins are otherwise only very weakly immunogenic. The HIV-1 vaccine field now uses the well-defined structures of trimeric Env glycoproteins, like SOSIPs, to present multiple known epitopes for broad and potent neutralizing human antibodies in a native-like conformation. Successful adjuvant formulations must not disrupt how the trimers are folded, as that could adversely affect their performance as immunogens. We studied whether the various adjuvants most commonly used in animal experiments affect the integrity of two different SOSIP trimersin vitro. Most adjuvant classes are not problematic, but an aluminum sulfate formulation is highly damaging, as it exposes trimers to acidic pH and a nucleic acid-based adjuvant can bind to the trimer and block access to a key neutralizing epitope.
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Gupta, Sachin, Emily S. Clark, James M. Termini, Justin Boucher, Saravana Kanagavelu, Celia C. LeBranche, Sakhi Abraham, David C. Montefiori, Wasif N. Khan, and Geoffrey W. Stone. "DNA Vaccine Molecular Adjuvants SP-D-BAFF and SP-D-APRIL Enhance Anti-gp120 Immune Response and Increase HIV-1 Neutralizing Antibody Titers." Journal of Virology 89, no. 8 (January 28, 2015): 4158–69. http://dx.doi.org/10.1128/jvi.02904-14.
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ABSTRACTBroadly neutralizing antibodies (bNAbs) specific for conserved epitopes on the HIV-1 envelope (Env) are believed to be essential for protection against multiple HIV-1 clades. However, vaccines capable of stimulating the production of bNAbs remain a major challenge. Given that polyreactivity and autoreactivity are considered important characteristics of anti-HIV bNAbs, we designed an HIV vaccine incorporating the molecular adjuvants BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand) with the potential to facilitate the maturation of polyreactive and autoreactive B cells as well as to enhance the affinity and/or avidity of Env-specific antibodies. We designed recombinant DNA plasmids encoding soluble multitrimers of BAFF and APRIL using surfactant protein D as a scaffold, and we vaccinated mice with these molecular adjuvants using DNA and DNA-protein vaccination strategies. We found that immunization of mice with a DNA vaccine encoding BAFF or APRIL multitrimers, together with interleukin 12 (IL-12) and membrane-bound HIV-1 Env gp140, induced neutralizing antibodies against tier 1 and tier 2 (vaccine strain) viruses. The APRIL-containing vaccine was particularly effective at generating tier 2 neutralizing antibodies following a protein boost. These BAFF and APRIL effects coincided with an enhanced germinal center (GC) reaction, increased anti-gp120 antibody-secreting cells, and increased anti-gp120 functional avidity. Notably, BAFF and APRIL did not cause indiscriminate B cell expansion or an increase in total IgG. We propose that BAFF and APRIL multitrimers are promising molecular adjuvants for vaccines designed to induce bNAbs against HIV-1.IMPORTANCERecent identification of antibodies that neutralize most HIV-1 strains has revived hopes and efforts to create novel vaccines that can effectively stimulate HIV-1 neutralizing antibodies. However, the multiple immune evasion properties of HIV have hampered these efforts. These include the instability of the gp120 trimer, the inaccessibility of the conserved sequences, highly variable protein sequences, and the loss of HIV-1-specific antibody-producing cells during development. We have shown previously that tumor necrosis factor (TNF) superfamily ligands, including BAFF and APRIL, can be multitrimerized using the lung protein SP-D (surfactant protein D), enhancing immune responses. Here we show that DNA or DNA-protein vaccines encoding BAFF or APRIL multitrimers, IL-12p70, and membrane-bound HIV-1 Env gp140 induced tier 1 and tier 2 neutralizing antibodies in a mouse model. BAFF and APRIL enhanced the immune reaction, improved antibody binding, and increased the numbers of anti-HIV-1 antibody-secreting cells. Adaptation of this vaccine design may prove useful in designing preventive HIV-1 vaccines for humans.
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Ceglia, Valentina, Sandy Zurawski, Monica Montes, Aurelie Bouteau, Zhiqing Wang, Jerome Ellis, Mitchell Kroll, Botond Z. Igyarto, Yves Levy, and Gerard Zurawski. "Dendritic cell targeting anti-CD40 antibody-CD40L-HIV-1 vaccines are adjuvant intrinsic." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 167.2. http://dx.doi.org/10.4049/jimmunol.204.supp.167.2.
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Abstract Soluble CD40L and agonistic anti-CD40 monoclonal antibody are adjuvants used in vaccination settings. Vaccines based on anti-CD40 antibodies fused to HIV-1 antigens are in clinical development. Studies with current anti-CD40-based dendritic cell (DC) targeting vaccines show that co-administration of an adjuvant is needed for maximal immune responses. We show that by fusing CD40L to CD40-targeting antibodies, activation of DCs concomitant with antigen uptake and processing is maximized, and this provides a context CD40-targeting vaccines with intrinsic adjuvant activity. Direct fusion of CD40L to L or H chain C-termini results in CD40 agonists with ‘superagonist’ properties. Especially on DCs, both potency and efficacy for induction of cytokine secretion and activation markers is greatly enhanced compared to known strong agonists like Pfizer’s anti-CD40 CP-870-89 antibody. This potency was maintained by anti-CD40-CD40L constructs fused to HIV-1 antigens from Gag, Nef, and Pol regions (HIV5pep). Anti-CD40-CD40L-HIV5pep preferentially expanded CD8+ T cells from HIV-1+ donor PBMCs compared to the same antibody-antigen fusions without attached CD40L. Anti-CD40-CD40L-TEα and anti-CD40-TEα both evoked robust proliferation of TEα-specific CD4+ T cells in human CD40 transgenic mice, but only anti-CD40-CD40L-TEα vaccine elicited TEα-specific CD4+ T cells producing IFNγ. Also, anti-CD40-CD40L-Env gp140 vaccine without adjuvant in human CD40 transgenic mice elicited stronger anti-Env gp140 antibody responses than anti-CD40-Env gp140 vaccine. Thus superagonist anti-CD40 antibodies directly fused to the natural ligand show great advantage in inducing immune responses without the use of an extrinsic adjuvant.
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Bui, Cac T., Lisa M. Shollenberger, Yvonne Paterson, and Donald A. Harn. "Schistosoma mansoni Soluble Egg Antigens Enhance Listeria monocytogenes Vector HIV-1 Vaccine Induction of Cytotoxic T Cells." Clinical and Vaccine Immunology 21, no. 9 (July 2, 2014): 1232–39. http://dx.doi.org/10.1128/cvi.00138-14.
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ABSTRACTVaccines are an important public health measure for prevention and treatment of diseases. In addition to the vaccine immunogen, many vaccines incorporate adjuvants to stimulate the recipient's immune system and enhance vaccine-specific responses. While vaccine development has advanced from attenuated organism to recombinant protein or use of plasmid DNA, the development of new adjuvants that safely increase immune responses has not kept pace. Previous studies have shown that the complex mixture of molecules that comprise saline soluble egg antigens (SEA) fromSchistosoma mansonieggs functions to promote CD4+T helper 2 (Th2) responses. Therefore, we hypothesized that coadministration of SEA with aListeriavector HIV-1 Gag (Lm-Gag) vaccine would suppress host cytotoxic T lymphocyte (CTL) and T helper 1 (Th1) responses to HIV-1 Gag epitopes. Surprisingly, instead of driving HIV-1 Gag-specific responses toward Th2 type, we found that coadministration of SEA with Lm-Gag vaccine significantly increased the frequency of gamma interferon (IFN-γ)-producing Gag-specific Th1 and CTL responses over that seen in mice administered Lm-Gag only. Analysis of the functionality and durability of vaccine responses suggested that SEA not only enlarged different memory T cell compartments but induced functional and long-lasting vaccine-specific responses as well. These results suggest there are components in SEA that can synergize with potent inducers of strong and durable Th1-type responses such as those toListeria. We hypothesize that SEA contains moieties that, if defined, can be used to expand type 1 proinflammatory responses for use in vaccines.
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Shollenberger, Lisa M., Stephanie K. Norwood, and Zachary J. Bement. "Development of alternative vaccination strategies to overcome Tc1 vaccine failure caused by chronic schistosomiasis." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 167.13. http://dx.doi.org/10.4049/jimmunol.204.supp.167.13.
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Abstract It is a global public health imperative to develop vaccine strategies that produce effective cell-mediated immunity in schistosome-endemic areas, such as sub-Saharan Africa, where HIV infection is common. Vaccine delivery techniques effective in immune-suppressed populations are critical to combating infectious diseases in these already compromised groups. It is well-known that immune suppression, such as by chronic schistosome infection, can cause Tc1/Th1 type vaccines to fail. Listeria, a strong inducer of cell-mediated immunity, can overcome the Th2 biasing and immune suppression caused by schistosome infection. However, safety concerns cause reluctance among the vaccine community and the public to incorporate this vector into immunization programs. Since neither DNA nor the Listeria vaccine vector are ideal for clinical translation, and Gag is likely not the ideal HIV vaccine antigen, we are using this system as a model for enumeration of Tc1 responses (IFNγ+ CD8+ cytotoxic T lymphocytes, CTL); CTLs are likely necessary components of functional responses for next-generation vaccines targeting diseases that currently lack effective vaccines (HIV, TB, malaria). Here, we investigate why DNA vaccine vectors fail during chronic schistosomiasis when Listeria vaccine vectors can generate robust CTL responses to HIV Gag. Specifically, we are examining live bacteria as adjuvants for an episomally expressed or concurrently administered DNA vaccine for HIV Gag. This project is one step toward our overall goal, which is to generate cell-mediated vaccine immunity in schistosome-infected, immune-suppressed patients.
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Vijayan, Mohapatra, Uthaman, and Park. "Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials." Pharmaceutics 11, no. 10 (October 14, 2019): 534. http://dx.doi.org/10.3390/pharmaceutics11100534.
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The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable vaccine candidates need to be designed to elicit appropriate immune responses. Nanotechnology has been found to play a unique role in the design of vaccines, providing them with enhanced specificity and potency. Nano-scaled materials, such as virus-like particles, liposomes, polymeric nanoparticles (NPs), and protein NPs, have received considerable attention over the past decade as potential carriers for the delivery of vaccine antigens and adjuvants, due to their beneficial advantages, like improved antigen stability, targeted delivery, and long-time release, for which antigens/adjuvants are either encapsulated within, or decorated on, the NP surface. Flexibility in the design of nanomedicine allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development. Biomimetic NPs have emerged as innovative natural mimicking biosystems that can be used for a wide range of biomedical applications. In this review, we discuss the recent advances in biomimetic nanovaccines, and their use in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and anti-tumor immunity.
Dissertations / Theses on the topic "HIV vaccine; adjuvants"
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Hanson, Melissa C. (Melissa Catherine). "Enhancement of HIV vaccine efficacy via lipid nanoparticle-based adjuvants." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/97975.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, February 2015..Cataloged from PDF version of thesis. "December 2014."
Includes bibliographical references (pages 93-108).
Adjuvants are immunomodulators and/or formulations/delivery vehicles which enhance immune responses to vaccines. The lack of progress in the development of an HIV humoral vaccine is due, in part, to the absence of available adjuvants which can be sufficiently potent with minimal adverse side effects. The main goal of this thesis was to develop nanoparticles as HIV vaccine adjuvants. Building upon previous work in the Irvine lab, we determined the potency of lipid-coated microparticles was due in part to the in situ generation of antigen-displaying liposomes. Synthetic liposomes were nearly as potent as lipid-coated microparticles, but with a 10-fold greater antigen conjugation efficiency. We subsequently optimized unilamellar liposomes as delivery vehicles for surface-displayed HIV antigens. For vaccines with a recombinant gpl20 monomer (part of the HIV envelope trimer), immunization at 0 and 6 weeks with 65 nm or 150 nm diameter liposomes with 7.5 pmol gpl20 was found to induce strong anti-gp120 titers which competed with the broadly-neutralizing antibody VRC01. The second HIV antigen used was a peptide derived from the membrane proximal external region (MPER) of the gp41 protein. High-titer IgG responses to MPER required the presentation of MPER on liposomes and the inclusion of molecular adjuvants such as monophosphoryl lipid A. Anti-MPER humoral responses were further enhanced optimizing the MPER density to a mean distance of -10-15 nm between peptides on the liposomes surfaces. Lastly, we explored the adjuvant potential of cyclic dinucleotides (CDNs) with MPER liposome vaccines. Encapsulation of CDN in PEGylated liposomes enhanced its accumulation in draining lymph nodes (dLNs) 15-fold compared to unformulated cyclic dinucleotide. Liposomal CDN robustly induced type I interferon in dLNs, and promoted durable antibody titers comparable to a 30-fold larger dose of unformulated CDN without the systemic toxicity of the latter. This work defines several key properties of liposome formulations that promote durable, high-titer antibody responses against HIV antigens and demonstrates the humoral immunity efficacy of nanoparticulate delivery of cyclic dinucleotides, which is an approach broadly applicable to small molecule immunomodulators of interest for vaccines and immunotherapy.
by Melissa C. Hanson.
Ph. D.
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Buglione-Corbett, Rachel. "Adjuvant-Specific Serum Cytokine Profiles in the Context of a DNA Prime-Protein Boost HIV-1 Vaccine: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/666.
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In recent years, heterologous prime-boost vaccination constructs have emerged as a promising strategy to generate broad and protective immunity against a variety of pathogens. The utility of DNA vaccination in priming the immune system, in particular, has improved the immunogenicity of vaccines against difficult pathogens such as HIV-1. In addition, many vaccine formulations include an adjuvant to augment immune responses. However, the mechanisms and profiles of many adjuvants remain largely unknown, particularly in the context of such combination immunization approaches.
My thesis research studied the effects of several adjuvants, QS-21, aluminum hydroxide, MPL, and ISCOMATRIX™ adjuvant in the context of a previously described pentavalent HIV-1 Env DNA prime-protein boost vaccine, DP6-001. In a murine model, we quantified HIV antigen-specific humoral and T cell responses, as well as pro-inflammatory serum cytokine and chemokines, both shortly after immunization and at the termination of studies. Our data indicates that each candidate adjuvant generates a unique pattern of biomarkers as well as improved immunogenicity in the context of the DP6-001 DNA prime-protein boost vaccine.
Additionally, we examined the impact of several innate signaling pathways on the adaptive immunity raised by DP6-001 and adjuvants, as well as on the unique serum cytokine profiles. These studies provide valuable information in selection of an adjuvant for inclusion in future prime-boost strategies, with the goal of enhancing immunogenicity while minimizing reactogenicity. Furthermore, these studies provided insight about the utility of different current adjuvants in a prime-boost formulation, and the unique immune environment induced by DNA priming.
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Buglione-Corbett, Rachel. "Adjuvant-Specific Serum Cytokine Profiles in the Context of a DNA Prime-Protein Boost HIV-1 Vaccine: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/666.
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In recent years, heterologous prime-boost vaccination constructs have emerged as a promising strategy to generate broad and protective immunity against a variety of pathogens. The utility of DNA vaccination in priming the immune system, in particular, has improved the immunogenicity of vaccines against difficult pathogens such as HIV-1. In addition, many vaccine formulations include an adjuvant to augment immune responses. However, the mechanisms and profiles of many adjuvants remain largely unknown, particularly in the context of such combination immunization approaches.
My thesis research studied the effects of several adjuvants, QS-21, aluminum hydroxide, MPL, and ISCOMATRIX™ adjuvant in the context of a previously described pentavalent HIV-1 Env DNA prime-protein boost vaccine, DP6-001. In a murine model, we quantified HIV antigen-specific humoral and T cell responses, as well as pro-inflammatory serum cytokine and chemokines, both shortly after immunization and at the termination of studies. Our data indicates that each candidate adjuvant generates a unique pattern of biomarkers as well as improved immunogenicity in the context of the DP6-001 DNA prime-protein boost vaccine.
Additionally, we examined the impact of several innate signaling pathways on the adaptive immunity raised by DP6-001 and adjuvants, as well as on the unique serum cytokine profiles. These studies provide valuable information in selection of an adjuvant for inclusion in future prime-boost strategies, with the goal of enhancing immunogenicity while minimizing reactogenicity. Furthermore, these studies provided insight about the utility of different current adjuvants in a prime-boost formulation, and the unique immune environment induced by DNA priming.
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Braga, Catarina Joelma Magalhães. "Pesquisa de novos adjuvantes para vacinas terapêuticas." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42132/tde-13022012-080631/.
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A busca por adjuvantes capazes de estimular eficiente resposta imunológica celular representa uma importante contribuição para a pesquisa de vacinas. No presente trabalho avaliamos o potencial adjuvante de flagelinas de Salmonella para a ativação de linfócitos T, com ênfase na ativação de linfócitos T CD8+, em animais imunizados com diferentes estratégias vacinais, desde vacinas baseadas em linhagens atenuadas de Salmonella; vacinas acelulares que empregaram flagelinas purificadas co-administradas, ou em fusão, a antígenos alvo e, ainda, vacinas de DNA. Nossos resultados demonstram que a utilização de flagelina na forma de vacina de DNA induziu maior proteção terapêutica que a mesma formulação utilizada na forma de vacinas de subunidades, sugerindo que os efeitos adjuvantes da flagelina para ativação de CTLs não estão relacionados apenas a ligação ao TLR5. Os resultados apresentados na presente tese contribuem para a compreensão dos mecanismos de adjuvanticidade da flagelina de Salmonella, particularmente no contexto da ativação de células T.The search for adjuvants that are able to stimulate an efficient cellular immune response represents an important contribution in vaccine development. In this study, we evaluated the potential of Salmonella flagellin as adjuvant for activation of T lymphocytes, with emphasis on the activation of CD8+ T cells, on the mice immunized with different approaches such as vaccines based on attenuated Salmonella strains; acellular vaccines with purified flagellin co-administered or genetically fusioned to the target antigen; or even DNA vaccines. Our results demonstrate that the use of flagellin in the form of DNA vaccines induced greater therapeutic protection than the same formulation used in the form of subunit vaccines, suggesting that the adjuvant effects of flagellin to the activation of CTLs are related not only to link to TLR5. The results presented in this work contribute significantly to the understanding of the mechanisms of flagellin adjuvanticity, particularly in the context of activation of responses mediated by T cells.
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Gutjahr, Alice. "Évaluation de combinaisons de ligands de PRR et de particules biodégradables pour la vaccination muqueuse." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1325.
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De nombreux obstacles freinent le développement d'un vaccin efficace contre le VIH. Pour franchir ces barrières, le recours aux adjuvants est une option prometteuse. Dans ce contexte, l'objectif de ce doctorat est l'évaluation de combinaisons de ligands de PRR et de particules biodégradables pour la vaccination muqueuse. La première partie de l'étude vise à analyser la valeur ajoutée de molécules hybrides composée de deux ligands de PRR comparée à la co-administration des deux agonistes. Des molécules stimulant TLR7 et TLR2 puis TLR7 et NOD2 ont été évaluées. Nous avons démontré l'intérêt de l'association de ligands de PRR au sein d'une même molécule, pour l'induction de réponses immunitaires systémiques et muqueuses. Des études récentes ont montré l'intérêt d'agonistes de STING comme adjuvant vaccinaux. Nous avons étudié l'induction de réponses immunitaires par les agonistes de STING, administrés par voie parentérale ou muqueuse. Nous avons démontré le fort potentiel de ligands de STING pour l'induction de réponses cellulaires et muqueuses. Lors de ces études, nous avons démontré que l'intérêt de la vectorisation d'agonistes de PRR dépend de la molécule. En effet, bien que la vectorisation d'une molécule hybride TLR7/TLR2 n'ait pas d'impact sur la réponse immunitaire induite, la vectorisation d'agonistes de STING potentialise leur effet immunostimulant. Pour finir, nous avons montré que la voie d'administration a un impact sur la réponse immunitaire induite. Afin de mieux comprendre les mécanismes mis en jeu, une étude de biodistribution des formulations de NP de PLA après administration par voie systémique ou muqueuse a été réaliséeThere are many barriers to the development an effective HIV vaccine. The use of adjuvants is a promising option to overcome these obstacles. In this context, the objective of this PhD is the evaluation of combinations of PRR ligands and biodegradable particles for mucosal vaccination.The first part of this study aimed at assessing the added value of hybrid molecules composed of two PRR ligands compared to the co-administration of the two agonists. TLR7 and TLR2 stimulating molecules followed by TLR7 and NOD2 were evaluated. We demonstrated the interest of the association of PRR ligands within the same molecule for the induction of systemic and mucosal immune responses.Recent studies showed the interest of STING agonists as a vaccine adjuvant. We investigated the induction of immune responses by STING agonists administered parenterally or mucosally. We confirmed the strong potential of STING ligands for the induction of cellular and mucosal responses.In these studies, we demonstrated that the interest of vectorization of PRR agonists depends on the molecule. Indeed, although the encapsulation of a TLR7/TLR2 hybrid molecule has no impact on the induced immune response, the vectorization of STING agonists potentiates their immunostimulatory effect.Finally, we showed that the route of administration has an impact on the immune response induced. In order to better understand the mechanisms involved, a biodistribution study of PLA NP formulations after systemic or mucosal administration was performed
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Xu, Lin. "HIV-1 mucosal immunity : from infection to prevention : HIV-1 envelope gp41 conserved region P1 modulates the mucosal innate immune response and acts as a potential mucosal adjuvant The HIV-1 viral synapse signals human foreskin keratinocytes to secrete thymic stromal lymphopoietin facilitating HIV-1 foreskin entry By shaping the antigen binding site in IgA, the CH1α domain is crucial for HIV-1 protection in highly exposed sero-negative individuals The antigen HIV-1 envelope gp41 conserved region P1 can act as mucosal adjuvant by modulating the innate immune response." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB071.
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La vaccination muqueuse, notamment celle administrée par voie nasale, est considérée comme la méthode optimale permettant de protéger les sites muqueux de l'infection par des pathogènes. Cependant, le manque d'adjuvants muqueux spécifiques ainsi qu'une prise en compte insuffisante du système immun nasal limite le développement des vaccins muqueux. P1, un domaine conservé de gp41, la glycoprotéine d'enveloppe du VIH-1, a été récemment utilisé par le laboratoire d'acceuil pour développer un vaccin prophylactique muqueux après immunisation combinée par voie nasale et intra-musculaire. Ce vaccin s'est montré efficace lors études pré-cliniques et clinique de Phase I chez l'Homme, grâce à sa capacité d'induire des IgA muqueux contre P1 bloquant la pénétration muqueuse du VIH-1 par transcytose et de stimuler la production d'IgG spécifiques de gp41 induisant la lyse des cellules infectées par le VIH-1 par cytotoxicité cellulaire médiée par anticorps (ADCC). Dans le travail présenté ici, nous avons caractérisé les mécanismes immuns induits par ce vaccin basé sur P1 au niveau de la muqueuse nasale humaine. Tout d'abord, nous avons démontré que P1 initie une réponse immune en induisant la sécrétion de la cytokine TH2, la Thymic Stromal LymphoPoietin (TSLP), par les cellules épithéliales nasales. TSLP est connyu pour ses propriétés d'adjuvant muqueux puissant et son récepteur, le TSLP-R, joue un rôle déterminant dans la réponse muqueuse à IgA. Nous avons montré que P1 induit l'expression de TSLP via l'interaction de P1 avec le galactosyl céramide, un récepteur du VIH-1 permettant l'entrée muqueuse du virus. De plus, nous avons identifié la voie de signalisation Calcineurin/NFATet le microRNA- comme partenaire décisifs dans la régulation de la production de TSLP induite par P1. Dans un second temps, nous avons montré que le peptide P1 module la réponse innée en activant les cellules dendritiques (DCs). Cette stimulation par P1 induit l'augmentation de l'expression des molécules de co-stimulation par les DCs. La sécrétion de l'IL-6 et de l'IL-10 par les DCs est aussi augmentée par P1 alors que celle de l'interféron gamma, IFN-', est réduite, démontrant ainsi que les DCs activée par P1 se polarisent en une phénotype facilitant une réponse Th2 et IgA. De plus, l'IL-8 et les chimiokines CCL20 et CCL22 sont secrétées indiquant que les DCs ont acquis la capacité de recruter des cellules immunes dans la muqueuse pour initier une réponse muqueuse adaptative. La métalloprotéinase MMP-9 permettant la dégradation de la matrice extracellulaire et facilitant la migration des cellules hors de la muqueuse, est aussi produite. Une boucle positive autocrine de TSLP est observée, puisque P1 induit la sécrétion par les DCs de TSLP en conséquence l'augmentation de l'expression du TSLP-R par les DCs induite par P1. Finalement, P1 active la prolifération des lymphocytes TCD4+ médiée par les DCs. En conclusion, nous avons démontré que P1 est un peptide multifonctionnel avec un grand potentiel dans le développement de vaccin, non seulement comme antigène vaccinal candidat mais aussi comme potentiel adjuvant qui pourrait être combinés à d'autres vaccins muqueuxMucosal vaccination, especially intranasal administrated ones, has been considered to be ideal for protection from pathogens invading through mucosal sites. However, the lack of specific adjuvant and insufficient acknowledgement of nasal immune system limits the development of vaccine. P1, a conserved region of gp41 envelope glycoprotein, was recently developed into a prophylactic HIV-1 vaccine immunized via both the intramuscular and intranasal routes. It showed high efficiency in pre-clinical and phase I clinical trial due to induction of P1 specific mucosal IgA with transcytosis blocking activity and IgG inducing antibody dependent cell cytotoxicity. In this study, we characterized the immunological mechanism underneath P1-vaccine in nasal mucosa. Firstly, we demonstrated that P1 initiate immune responses by inducing nasal epithelial cells to secret the Th2 cytokine Thymic Stromal LymphoPoietin (TSLP). TSLP has been reported to be a strong mucosal adjuvant, and its receptor TSLP-R plays a critical role in IgA response. We showed that P1 induce TSLP expression via the interaction with galactosyl ceramide, the receptor of HIV-1 mucosal entry. Furthermore, we identified Calcineurin/NFAT signaling pathway and microRNA-4485 as important players in the regulation of TSLP production induced by P1. Secondly, we showed that P1 modulates innate immune responses by activate dendritic cells (DCs). P1 stimulation results in enhanced expression of costimulatory molecules on DCs. Furthermore, the secretion of IL-6, IL-10 were increased, while IFN-γ was reduced, indicating that P1 activated DCs polarize into a Th2 and IgA prone phenotype. In addition, IL-8, CCL20, CCL22 were produced indicating a capacity at recruiting immune cells to mucosal surface for initiation of an adaptive immune response. MMP-9 was also produced allowing degradation of the extracellular matrix and facilitating the migration of immune cells out of the mucosa. Stricingly, a TSLP autocrine loop was observed as P1 induced DCs to secret TSLP and meanwhile, enhanced DC expression of TSLP-R. Finally, P1 activated DCs enhanced the proliferation of CD4+ T cells. In conclusion, we demonstrated that P1 is a multi-functional protein with a great interest for vaccine development, not only as an antigen for vaccine candidate, but also as a potential adjuvant that can be combined to other mucosal vaccines
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Brinckmann, Sarah Anna. "Polyethyleneimine as a candidate vaccine adjuvant for Env-based HIV-1 infection." Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559758.
Full textAbstract:
Almost 30 years after the identification of HIV-I as the causative agent of AIDS, an effective prophylactic HIV-I vaccine has yet to be developed. Despite the design of a vast array of therapeutic agents and prevention strategies, which have helped to reduce AIDS mortality and the growth of the pandemic, HIV-I is still the fourth biggest killer worldwide and an effective vaccine will be needed to halt the pandemic. Over the past three decades, various HIV-I vaccination strategies have been explored leading to the key understanding that sterile protection against HIV-I infection will require a combination of cellular and humoral responses, particularly at the mucosal compartment, the common route of infection. Consequently, it has been postulated that this can only be achieved through a potent and effective immunisation strategy involving mucosal immunisation and the application of a heterologous prime-boost regimen. However, the mucosal route of immunisation, in particular for subunit vaccines, has not been well established as a mainstream mode of vaccination in human and results with experimental mucosal immunisation have generally been impeded by a lack of safe and effective mucosal adjuvants. In the work presented herein, I investigated whether the highly cationic polyethyleneimine (PEI), a gold standard DNA delivery agent, has adjuvant activity applied parenterally and mucosally in formulation with glycoprotein antigens, in particular HIV-I Env gp140, the sole target of neutralising antibodies (nAbs) and therefore the most attractive HIV-I sub unit vaccine candidate. I demonstrated that PEI is a potent inducer of Env-specific Ab responses in a mixed Ti.l and Th2 context. PEI is particularly potent via the mucosal route and superior to gold standard mucosal adjuvant Cholera Toxin Beta subunit (CTB) as measured by HIV-I specific IgA responses at the mucosal compartment. PEI showed direct immune stimulatory effects, marked by a significant recruitment of local leukocytes, including inflammatory monocytes and dendritic cells (DCs). Further it associated with antigen to form gpI40-PEI particles, which enhanced antigen targeting to, and uptake by, immune cells, in particular monocytes, macro phages, and DCs. The observed adjuvant activity was maintained with the use of various forms of PEI, including linear or branched, and durable or biodegradable, and under a range in molecular weight (MW), suggesting that immune potentiation is a shared attribute of this group of PEI polymers. This is the first demonstration of PEI as a mucosal adjuvant for protein immunisation. These results merit further exploration of PEI in protection models with the implication for clinical trials.
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Bridge, Simon Harwood. "HIV-Neutralising response to recombinant, cross-clade, adjuvanted, VLP-forming vaccine candidates." Thesis, University of Liverpool, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485898.
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The development of a safe, effective and affordable HIV-1 vaccine is urgently needed especially in resource poor settings. It is widely accepted that for a vaccine to confer sterilising immunity to HIV-1 it will have to elicit broadly neutralising antibodies (nAbs) to primary isolates of HIV but this goal has remained elusive. There are two key problems to be addressed in this regard: vaccine candidates have to express the correct epitopes capable of eliciting broadly cross-reactive neutralising antibodies to HIV, and they have to provide potent stimulatory signals to the relevant B cells so that high titres ofneutralising antibodies are obtained. Plasmid DNA and recombinant poxviruses such as modified vaccinia virus Ankara (MYA) and fowlpox virus (FPV) have been safely administered to humans and offer the advantage of accommodating large amounts of additional recombinant DNA. In addition, they have provided promising cytotoxic T-Iymphocyte inducing HIV-l vaccine candidates, especially in heterologous prime-boost combinations. The hypothesis investigated here is that sequentially immunising with envelopes of different clades of HIV might lead to the antibody response being focussed on neutralising epitopes held in common. To overcome the poor immunogenicity of cross-clade neutralising epitopes, and the generally poor antibody responses elicited to priming with DNA, followed by boosting with recombinant poxviruses, B cells were stimulated by the coexpression of cholera toxin B and human complement component C3d. To further stimulate antibody production the candidate vaccines coencoded envelope and capsid components so that there would be in vivo virus-like particle formation. The candidate HIV vaccines proceeded directly to a non-human primate study of immunogenicity because this model most closely resembles the immune response in humans, and the benefits of virus-like particle formation and the adjuvant effect ofhuman C3d were most likely to be demonstrated. The work in this thesis describes the construction and characterisation of complex, adjuvanted poxviral recombinants for use as HIV vaccine candidates in a DNA primeFPV boost-MVA boost in macaques and the subsequent efficacy of macaque sera to neutralise primary isolates ofHIV-l in a validated HIV-l neutralisation assay.
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Khodami, Pantea. "An evaluation of novel lipid-enveloped nanoparticles for adjuvant and antigen delivery for an HIV vaccine : stepping from laboratory into potential markets." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/62742.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, February 2011."February 2011." Cataloged from PDF version of thesis.
Includes bibliographical references (p. 69-80).
Enormous effort has been devoted to the development of a vaccine against human immunodeficiency virus (HIV). The purpose of this paper is to evaluate the technological and economical aspects of a potential vaccine designed by Professor Irvine's group. Lipid-enveloped virion-sized nano-particles with a biodegradable polymer core are used as synthetic pathogens to deliver HIV specific antigens and adjuvants. The nano-particles are designed to display multiple copies of the antigen on their surfaces and to elicit humoral immunity response. Topics such as patent ability, obtaining an FDA licensure, storage, cost of manufacturing, and supply of the vaccine are explored. A business model for commercialization of the vaccine is outlined, and some possible future business opportunities for the nano-particles are discussed.
by Pantea Khodami.
M.Eng.
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Smith, Jeffrey D. "Vaccination of BALB/c Mice with an Alhydrogel Adjuvanted Whole Cell Trichomonas vaginalis Formulation." Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/30424.
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A human safe, Alhydrogel adjuvanted whole cell Trichomonas vaginalis vaccine was tested for efficacy in a BALB/c mouse model of vaginal infection. Additionally, the systemic and local immune response were measured. Vaccination reduced incidence and increased clearance of infection, and induced both systemic and local humoral immune responses. CD4+ cells were detected in vaginal tissues following intravaginal challenge with T. vaginalis, but were not seen in uninfected mice. CD4+ cells were detected more often, earlier, and in greater numbers in vaccinated vaginal tissues compared to unvaccinated controls. Presence of CD4+ T cells following infection can have significant implications of increasing HIV susceptibility and transmission. These data suggest that the vaccine induces local and systemic immune responses, and confers significantly greater protection against vaginal challenge than unvaccinated vaginal challenge. These data support the potential for a human vaccine against T. vaginalis infection that could also impact the incidence of HIV infections.
Books on the topic "HIV vaccine; adjuvants"
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International, Symposium on the Immunobiology of Proteins and Peptides (6th 1990 Scottsdale Ariz ). Immunobiology of proteins and peptides VI: Human immunodeficiency virus, antibody immunoconjugates, bacterial vaccines, and immunomodulators. New York: Plenum Press, 1991.
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Immunobiology of Proteins and Peptides VI: Human Immunodeficiency Virus, Antibody immunoconjugates, Bacterial Vaccines, Immunomodulators (Advances in Experimental Medicine and Biology). Springer, 1992.
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Atassi, M. Zouhair. Immunobiology of Proteins and Peptides VI: Human Immunodeficiency Virus, Antibody Immunoconjugates, Bacterial Vaccines, and Immunomodulators. Springer London, Limited, 2012.
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Atassi, M. Zouhair. Immunobiology of Proteins and Peptides Vi: "Human Immunodeficiency Virus, Antibody Immunoconjugates, Bacterial Vaccines, And Immunomodulators". Springer, 2012.
Find full textBook chapters on the topic "HIV vaccine; adjuvants"
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Rizza, Paola, Imerio Capone, and Filippo Belardelli. "Adjuvants, Dendritic Cells, and Cytokines: Strategies for Enhancing Vaccine Efficacy." In The Biology of Dendritic Cells and HIV Infection, 171–202. Boston, MA: Springer US, 2007. http://dx.doi.org/10.1007/978-0-387-33785-2_5.
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Ray, Shilpa, and Mrutyunjay Suar. "Vaccine Nanocarriers." In Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering, 221–68. IGI Global, 2015. http://dx.doi.org/10.4018/978-1-4666-6363-3.ch012.
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Vaccination has undergone a complete revolution over the past ten decades. With the progress in biotechnology, the present scientific world has witnessed the emergence of a novel vaccine delivery system, called nanovaccines, for eliciting effective humoral, cellular, and mucosal immunity as compared to the conventional vaccination strategies. This novel approach bears innovative methodologies for effective vaccination by arousing beneficial host responses. The different forms of nanovaccine delivery are either microspheres or nanobeads. This chapter discusses in detail the variant forms of nanoparticulate vaccine adjuvants and delivery systems, their interaction with the immune system, and their clinical trial results. Many nanovaccines licensed for human use have proved to be effective carriers for antigens. These immunopotentiators like virosome-based carriers, Immunostimulating Complexes (ISCOMs), polymeric particles, etc. can be formulated as new vaccination methods for curing diseases like HIV, malaria, hepatitis, cancer, etc., thereby cementing the future of the next generation vaccines.
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Ray, Shilpa, and Mrutyunjay Suar. "Vaccine Nanocarriers." In Biomedical Engineering, 1353–401. IGI Global, 2018. http://dx.doi.org/10.4018/978-1-5225-3158-6.ch058.
Full textAbstract:
Vaccination has undergone a complete revolution over the past ten decades. With the progress in biotechnology, the present scientific world has witnessed the emergence of a novel vaccine delivery system, called nanovaccines, for eliciting effective humoral, cellular, and mucosal immunity as compared to the conventional vaccination strategies. This novel approach bears innovative methodologies for effective vaccination by arousing beneficial host responses. The different forms of nanovaccine delivery are either microspheres or nanobeads. This chapter discusses in detail the variant forms of nanoparticulate vaccine adjuvants and delivery systems, their interaction with the immune system, and their clinical trial results. Many nanovaccines licensed for human use have proved to be effective carriers for antigens. These immunopotentiators like virosome-based carriers, Immunostimulating Complexes (ISCOMs), polymeric particles, etc. can be formulated as new vaccination methods for curing diseases like HIV, malaria, hepatitis, cancer, etc., thereby cementing the future of the next generation vaccines.
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Shahid, Imran, and Qaiser Jabeen. "Appling Drug Discovery in HCV-therapeutics: A snapshot from the past and glimpse into the future." In Hepatitis C Virus-Host Interactions and Therapeutics: Current Insights and Future Perspectives, 290–342. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815123432123010013.
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The ongoing COVID-19 pandemic with its devastating impacts in terms of huge disease burden and patient management on the world’s leading healthcare systems and jolting the world’s biggest economies, has leveraged the lesson that to prevent the transmission and elimination of a viral pandemic, endemic, or epidemic in future, a prophylactic or protective vaccine would be indispensable. In this scenario, DAAs regimens alone would not be sufficient to eliminate the HCV epidemic by 2030 or beyond and there would always be the demand for a prophylactic or protective vaccine to prevent the transmission of this epidemic again from vulnerable populations. The anti-mRNA-based treatment strategies (e.g., anti-HCV protein-specific oligonucleotides, RNA interference (RNAi), and micro RNA (miRNA)), and some potential anti-hepatitis C vaccine models have been widely and extensively studied as an alternative or adjuvant therapeutic approaches for hepatitis C in the recent past and some of those models are still in the pipeline. The approval of the first RNAi therapy against a hereditary protein deposition disorder has urged investigators to refocus this approach against hepatitis C because it represents the most thoroughly studied treatment strategy against hepatitis C in the last two decades. Furthermore, some emerging approaches like host targeting agents (HTA), nanoparticles-containing immunogens, and nanomedicine-based therapeutic agents are also in their full investigative form. In this book chapter, we will discuss and highlight emerging hepatitis C treatment approaches that could be the game-changer to vanquishing HCV by 2030 while used as an adjuvant or compensatory regimen with DAAs.
Conference papers on the topic "HIV vaccine; adjuvants"
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Farache Trajano, Luiza, Rebecca Moore, and Quentin Sattentau. "The Presence of Chemical Cross-Linking Stabilises HIV-1 Envelope Glycoprotein Trimer Antigens in a Model of Intramuscular Immunisation." In Building Bridges in Medical Science 2021. Cambridge Medicine Journal, 2021. http://dx.doi.org/10.7244/cmj.2021.03.001.4.
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Background: The HIV-1 envelope glycoprotein (Env) is the target of antigen design for antibody- based vaccination. In 2019, four trimeric Env vaccines entered an experimental trial: ConM, ConS, and their cross-linked counterparts. The trimers were formulated with MPLA adjuvant. Studies have demonstrated that adjuvants trigger neutrophil infiltration. Neutrophils activate and degranulate releasing proteases, namely elastase and cathepsinG. Aims: To assess the stability and immunogenicity of these vaccines in the presence of adjuvant- recruited neutrophils and their proteolytic enzymes. Methods: Trimers were incubated with commercially-sourced proteases. To analyse stability, samples were reduced, denatured and separated using gel electrophoresis. To assess antibody binding, a trimer-protease incubation was followed by an ELISA. To establish more physiologically relevant conditions, harvested neutrophils were exposed to various adjuvants. The supernatant, shown to contain elastase, was incubated alongside the vaccines. The reducing and denaturing gels, as well as the ELISA, was repeated. Results: Gel analysis revealed that un-crosslinked trimers underwent significant digestion whereas cross-linking conferred enhanced stability. In the presence of neutrophil-sourced protease-containing-supernatant, trimers displayed resistance to digestion. The differential stability profile of Env trimers when exposed to commercially sourced compared to supernatant- derived proteases may be due to the inhibitory effect of human serum on elastase. Antibody epitopes were maintained in vitro. Conclusion: The vaccine antigens are sensitive to enzymatic degradation. This is reduced by cross-linking and human serum.
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Krishnakumar, D., and K. S. Jaganathan. "Development of nasal HPV vaccine formulations." In 16th Annual International Conference RGCON. Thieme Medical and Scientific Publishers Private Ltd., 2016. http://dx.doi.org/10.1055/s-0039-1685403.
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Cervical cancer is the second most cancer in women worldwide with over 500000 new cases and 275000 deaths being registered every year. With nearly 73000 women dying every year, India now tops the world in cervical cancer deaths. India represents 26.4% of all women dying of cervical cancer globally. Cervical cancer estimated to be responsible for about 5% of human cancers worldwide. Currently available vaccines may not provide complete protection against all HPV types as the protection is primarily type specific. Furthermore, the available vaccines are delivered via intramuscular route and require three doses and require cold chain supply which increases the cost of vaccine. Therefore a single dose vaccine delivered via non-invasive route (nasal) that protects against multiple HPV types would be a cost effective and better alternative to the currently available HPV vaccines. The main objective of this study was to prepare HPV antigen loaded poly (lactic-co-glycolic acid) (PLGA) and Tri Methyl Chitosan (TMC) coated PLGA microparticles and compare their efficacy as nasal vaccine. The developed formulations were characterized for size, zeta potential, entrapment efficiency, mucin adsorption ability, in vitro and in vivo studies. PLGA microparticles demonstrated negative zeta potential whereas PLGA-TMC microparticles showed higher positive zeta potential. The protein loading efficiency was found as above 80%. Results indicated that PLGA-TMC microparticles demonstrated substantially higher mucin adsorption when compared to PLGA microparticles. HPV antigen encapsulated in PLGA-TMC particles elicited a significantly higher secretory (IgA) immune response compared to that encapsulated in PLGA particles. Present study demonstrates that PLGA-TMC microparticles with specific size range can be a better carrier adjuvant for nasal subunit vaccines. Surface modified PLGA microparticles proved great potential as a nasal delivery system for HPV infections where systemic and mucosal responses are necessary particularly in conditions after viral pathogens invade the host through the mucosal surface.
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Gonçalves, Ana Katherine, Paulo César Giraldo, Kleber Juvenal Farias, Paula Renata Machado, Ana Paula Ferreira Costa, Luanda Canário De Souza, Janaina Cristiana Crispim, José Eleutério Júnior, and Steven Sol Witkin. "P1.03 Characterisation of immunoglobulin a/g responses during 3 doses of the human papillomavirus-16/18 aso4-adjuvanted vaccine." In STI and HIV World Congress Abstracts, July 9–12 2017, Rio de Janeiro, Brazil. BMJ Publishing Group Ltd, 2017. http://dx.doi.org/10.1136/sextrans-2017-053264.111.
Full textReports on the topic "HIV vaccine; adjuvants"
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Pinto, Angelo J. Efficacy of the Heat-Labile Enterotoxin from Escherichia Coli as an Adjuvant for a HSV-2 Inactivated Oral Vaccine. Fort Belvoir, VA: Defense Technical Information Center, March 1996. http://dx.doi.org/10.21236/ada312064.
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