Статті в журналах: "Heterologous prime-boost"

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Lu, Shan. "Heterologous prime–boost vaccination." Current Opinion in Immunology 21, no. 3 (June 2009): 346–51. http://dx.doi.org/10.1016/j.coi.2009.05.016.

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Pan, Chien-Hsiung, Hui-mei Hu, Yu-Ju Hsiao, and Sze-Hsien Wu. "Heterologous prime-boost vaccination with DNA vaccine and recombinant subunit containing four serotypes of dengue virus envelope protein domain III elicits neutralizing antibodies and specific T-cell responses (P4327)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 123.27. http://dx.doi.org/10.4049/jimmunol.190.supp.123.27.

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Abstract Dengue is still an important public health problem and no dengue vaccine is available now. In this study, we characterized prime-boost vaccine regimens using heterologous and homologous dengue DNA vaccine and recombinant subunit vaccine consisted of envelope (E) protein domain III (ED III) from four serotypes of dengue virus (DENV). A broader and balanced IFN-gamma and IL-4 responses was observed in DNA-prime and subunit-boost immunized mice, compared to a narrower but strong IFN-gamma production after homologous DNA vaccination and an IL-4 only response in homologous subunit vaccine immunized mice. In addition, a significant ED III specific antibody response was detected in all immunized mice except vector control. The highest IgG titer was appeared in homologous subunit vaccine immunized mice, followed by heterologous prime-boost regimen and homologous DNA vaccine. However, that heterologous prime-boost immunized mice generated a highest neutralizing antibody than the others, suggested a better protection provided by this DNA-prime and subunit vaccine-boost regimen.

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Tang, Xian, and Zhiwei Chen. "Heterologous immunization induces potent anti-SIV immunity with qualitative and quantitative improvements (53.22)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 53.22. http://dx.doi.org/10.4049/jimmunol.186.supp.53.22.

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Abstract Background: The live replication-competent modified vaccinia virus Tiantan (MVTT) is an attractive vaccine vector. In this study, we constructed a recombinant MVTT expressing SIV Gag-Pol and Env (MVTT-SIV) and compared its efficacy for inducing antigen-specific immunity when administrated in different routes with or without rAd5-based vaccine encoding the same antigens (rAd5-SIV). Methods: MVTT-SIV was tested for its immunogenicity in mice administered homologously by a prime-boost strategy or heterologously in combination with rAd5-SIV. The prime routes included intranasal (IN), sublingual (SL), oral, mixed (mix of the previous three musocal routes) or intramuscular (IM) injection. All groups received IM boost. Result: Mice given heterologous boost produced significantly greater SIV specific T cell and Gag-specific antibody responses than homologous boost groups. Besides, heterologous immunization generated much higher level of neutralizing antibodies, despite of the lower titers of Env-specific binding antibodies according to Elisa assay. Moreover, the immunogenicity of MVTT-SIV given by mixed route followed by rAd5-SIV intramuscular boost was unique in terms of anti-SIV cellular and humoral immunity. Conclusion: Heterologous immunization induces potent anti-SIV Immunity with improvements in quality and quantity. The combination of MVTT-SIV mixed prime and rAd5-SIV intramuscular boost may be an effective and protective vaccination strategy in further studies.

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ZHANG, G., V. T. T. HUONG, B. BATTUR, J. ZHOU, H. ZHANG, M. LIAO, O. KAWASE, et al. "A heterologous prime-boost vaccination regime using DNA and a vaccinia virus, both expressing GRA4, induced protective immunity againstToxoplasma gondiiinfection in mice." Parasitology 134, no. 10 (May 17, 2007): 1339–46. http://dx.doi.org/10.1017/s0031182007002892.

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SUMMARYThe dense granule antigen 4 (GRA4) is known as an immundominant antigen ofToxoplasma gondiiand, therefore, is considered as a vaccine candidate. For further evaluation of its vaccine effect, a recombinant plasmid and vaccinia virus, both expressing GRA4, were constructed, and a heterologous prime-boost vaccination regime was performed in a mouse model. The mice immunized with the heterologous prime-boost vaccination regime showed a high level of specific antibody response against GRA4 and a significantly high level of gamma interferon (IFN-γ) production and survived completely against a subsequent challenge infection with a lethal dose ofT. gondii. In addition, the formation of cysts was inhibited in the mice vaccinated with the heterologous prime-boost vaccination regime. These results demonstrate that the heterologous prime-boost vaccination regime using DNA and a vaccinia virus, both expressing GRA4, could induce both humoral and cellular immune responses and provide effective protection against lethal acute and chronicT. gondiiinfections in mice.

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5

Garg, Ishan, Abu Baker Sheikh, Suman Pal, and Rahul Shekhar. "Mix-and-Match COVID-19 Vaccinations (Heterologous Boost): A Review." Infectious Disease Reports 14, no. 4 (July 20, 2022): 537–46. http://dx.doi.org/10.3390/idr14040057.

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Various safe and effective COVID-19 vaccines utilizing different platforms (mRNA, adenovirus vector, inactivated virus-based) are available against SARS-CoV-2 infection. A prime-boost regimen (administration of two doses) is recommended to induce an adequate and sustained immune response. Most of these vaccines follow a homologous regimen (the same type of vaccine as priming and booster doses). However, there is a growing interest in a heterologous prime-boost vaccination regimen to potentially help address concerns posed by fluctuating vaccine supplies, serious adverse effects (anaphylaxis and thromboembolic episodes following adenovirus-based vaccines), new emerging virulent strains, inadequate immune response in immunocompromised individuals, and waning immunity. Various studies have demonstrated that heterologous prime-boost vaccination may induce comparable or higher antibody (spike protein) titers and a similar reactogenicity profile to the homologous prime-boost regimen. Based on these considerations, the Center for Disease Control and Prevention has issued guidance supporting the “mix-and-match” heterologous boost COVID-19 vaccine strategy.

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Folegatti, Pedro M., Amy Flaxman, Daniel Jenkin, Rebecca Makinson, Lucy Kingham-Page, Duncan Bellamy, Fernando Ramos Lopez, et al. "Safety and Immunogenicity of Adenovirus and Poxvirus Vectored Vaccines against a Mycobacterium Avium Complex Subspecies." Vaccines 9, no. 3 (March 16, 2021): 262. http://dx.doi.org/10.3390/vaccines9030262.

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Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as a booster vaccine following a simian adenovirus (ChAdOx2) prime. We demonstrate that a heterologous prime-boost schedule is well tolerated and induced T-cell immune responses.

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Carlétti, Dyego, Denise Morais da Fonseca, Ana Flávia Gembre, Ana Paula Masson, Lívia Weijenborg Campos, Luciana C. C. Leite, Andréa Rodrigues Pires, et al. "A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice." Clinical and Vaccine Immunology 20, no. 8 (June 5, 2013): 1162–69. http://dx.doi.org/10.1128/cvi.00148-13.

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ABSTRACTMycobacterium bovisBCG prime DNA (Mycobacterium tuberculosisgenes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted byM. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratrachealM. tuberculosischallenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carryingapaand 6,6′-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

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Dai, Ming-Shen, Ren-In You, Yu-Feng Hsieh, Kai-Yu Lo, Huey-Kang Sytwu, Georges Vassaux, and Tsu-Yi Chao. "Early Treg suppression by a Listeriolysin-O-expressing E. coli vaccine in heterologous prime-boost vaccination against cancer (165.49)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 165.49. http://dx.doi.org/10.4049/jimmunol.186.supp.165.49.

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Abstract [Background] Earlier studies have shown that higher CD8+ T-cell response and better tumor protection can be achieved by heterologous prime-boost vaccination in mice. We previously demonstrated that a Listeriolysin-O (LLO)-expressing E. coli vaccine can enhanced CD8-cytotoxic T cell (CTL) responses by mitigating regulatory T cells (Treg)-mediated suppression. We herein employed this Treg-inhibiting vaccine into the prime/boost immunization strategy. [Methods] Bacteria E. coli-LLO expressing Ovalbumin (OVA) and plasmid pcDNA—encoding OVA were used as specific antigen immunization. C57B6 mice and syngenic melanoma cell line B16-OVA were used in tumor challenge model. CD25 monoclonal antibody (PC-61) was used for Treg depletion. [Results] Higher OVA-specific CD8+ T-cell responses and superior tumor inhibition were seen in the bacterial-prime/plasmid-boost setting than homologous or reversed sequence. This tumor protection effect from heterologous prime/boost remained significant in the therapeutic model. When examining the Treg effect during the prime/boost immunization, we found that only early Treg-suppression/depletion could lead to better antigen-specific CTL and tumor response. [Conclusion] Our studies offer the first evidence that a Listeriolysin-O E. coli vaccine can induce superior anti-tumor effect in conjunction with DNA in a heterologous prime-boost protocol and proposed that early Treg inhibition is crucial to a successful immunization against cancer.

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Santra, Sampa, Yue Sun, Jenny G. Parvani, Valerie Philippon, Michael S. Wyand, Kelledy Manson, Alicia Gomez-Yafal, et al. "Heterologous Prime/Boost Immunization of Rhesus Monkeys by Using Diverse Poxvirus Vectors." Journal of Virology 81, no. 16 (June 6, 2007): 8563–70. http://dx.doi.org/10.1128/jvi.00744-07.

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ABSTRACT As the diversity of potential immunogens increases within certain classes of vectors, the possibility has arisen of employing heterologous prime/boost immunizations using diverse members of the same family of vectors. The present study was initiated to explore the use of divergent pox vectors in a prime/boost regimen to elicit high-frequency cellular immune responses to human immunodeficiency virus type 1 envelope and simian immunodeficiency virus gag in rhesus monkeys. We demonstrated that monkeys vaccinated with a recombinant modified vaccinia virus Ankara (rMVA) prime/recombinant fowlpox virus (rFPV) boost regimen and monkeys vaccinated with a recombinant vaccinia virus prime/rFPV boost regimen developed comparable cellular immune responses that were greater in magnitude than those elicited by a homologous prime/boost with rMVA. Nevertheless, comparable magnitude recall cellular immune responses were observed in monkeys vaccinated with heterologous and homologous recombinant poxvirus following challenge with the CXCR4-tropic SHIV-89.6P. Consistent with this finding, comparable levels of containment of viral replication and CD4+ T-lymphocyte preservation were seen in these groups of recombinant poxvirus-vaccinated monkeys. This study supports further exploration of combining recombinant vectors of the same family in prime/boost immunization strategies to optimize vaccine-elicited cellular immune responses.

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Kaku, Chengzi I., Elizabeth R. Champney, Johan Normark, Marina Garcia, Carl E. Johnson, Clas Ahlm, Wanda Christ, et al. "Broad anti–SARS-CoV-2 antibody immunity induced by heterologous ChAdOx1/mRNA-1273 vaccination." Science 375, no. 6584 (March 4, 2022): 1041–47. http://dx.doi.org/10.1126/science.abn2688.

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Heterologous prime-boost immunization strategies have the potential to augment COVID-19 vaccine efficacy. We longitudinally profiled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)–specific serological and memory B cell (MBC) responses in individuals who received either homologous (ChAdOx1:ChAdOx1) or heterologous (ChAdOx1:mRNA-1273) prime-boost vaccination. Heterologous messenger RNA (mRNA) booster immunization induced higher serum neutralizing antibody and MBC responses against SARS-CoV-2 variants of concern (VOCs) compared with that of homologous ChAdOx1 boosting. Specificity mapping of circulating B cells revealed that mRNA-1273 boost immunofocused ChAdOx1-primed responses onto epitopes expressed on prefusion-stabilized S. Monoclonal antibodies isolated from mRNA-1273–boosted participants displayed overall higher binding affinities and increased breadth of reactivity against VOCs relative to those isolated from ChAdOx1-boosted individuals. Overall, the results provide molecular insight into the enhanced quality of the B cell response induced after heterologous mRNA booster vaccination.

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Shaw, Robert H., Arabella Stuart, Melanie Greenland, Xinxue Liu, Jonathan S. Nguyen Van-Tam, and Matthew D. Snape. "Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data." Lancet 397, no. 10289 (May 2021): 2043–46. http://dx.doi.org/10.1016/s0140-6736(21)01115-6.

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Michael, Nelson L. "Simplified steps to heterologous prime-boost HIV vaccine development?" Journal of Clinical Investigation 129, no. 11 (September 30, 2019): 4572–73. http://dx.doi.org/10.1172/jci132440.

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Gu, Yuan, Bin Zhan, Yaping Yang, Xiaodi Yang, Xi Zhao, Lei Wang, Jing Yang, Kuo Bi, Yunyun Wang, and Xinping Zhu. "Protective Effect of a Prime-Boost Strategy with the Ts87 Vaccine againstTrichinella spiralisInfection in Mice." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/326860.

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Trichinellosis is a widespread zoonosis primarily caused byTrichinella spiralis. Mucosal immunity is crucial for preventingTrichinella spiralisinfection. In our previous study, a DNA vaccine with theTrichinellaantigen Ts87 delivered by an attenuatedSalmonella typhimuriumelicited partial protection againstTrichinella spiralisinfection in mice. In the current study, to elicit a more robust immune response and develop a potent vaccination strategy against trichinellosis, a heterologous prime-boost vaccination regimen for Ts87 was used in mice and the protective efficacy was evaluated compared to the homologous DNA prime-boost or protein prime-boost immunization alone. The results revealed that the DNA-prime/protein-boost vaccination with Ts87 induced higher levels of both humoral and cellular immune responses. The challenge results showed that mice with the DNA-prime/protein-boost vaccination displayed higher muscle larval reduction than those immunized with DNA prime-boost or protein prime-boost. The results demonstrated that mice vaccinated with Ts87 in a DNA-prime/protein-boost strategy effectively elicited a local IgA response and mixed Th1/Th2 immune response that might be responsible for improved protection againstTrichinella spiralisinfection.

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Hofer, Tamara, Matteo Rossi, Susanna Carboni, Wilma Di Berardino Besson, Dorothee von Laer, Guido Wollmann, Madiha Derouazi, and Marie-Laure Santiago-Raber. "Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect." Cancers 13, no. 23 (December 3, 2021): 6107. http://dx.doi.org/10.3390/cancers13236107.

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Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.

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Xiao, Minglu, Luoyingzi Xie, Guoshuai Cao, Shun Lei, Pengcheng Wang, Zhengping Wei, Yuan Luo, et al. "CD4⁺ T-cell epitope-based heterologous prime-boost vaccination potentiates anti-tumor immunity and PD-1/PD-L1 immunotherapy." Journal for ImmunoTherapy of Cancer 10, no. 5 (May 2022): e004022. http://dx.doi.org/10.1136/jitc-2021-004022.

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BackgroundAntitumor therapeutic vaccines are generally based on antigenic epitopes presented by major histocompatibility complex (MHC-I) molecules to induce tumor-specific CD8+ T cells. Paradoxically, continuous T cell receptor (TCR) stimulation from tumor-derived CD8+ T-cell epitopes can drive the functional exhaustion of tumor-specific CD8+ T cells. Tumor-specific type-I helper CD4+ T (TH1) cells play an important role in the population maintenance and cytotoxic function of exhausted tumor-specific CD8+ T cells in the tumor microenvironment. Nonetheless, whether the vaccination strategy targeting MHC-II-restricted CD4+ T-cell epitopes to induce tumor-specific TH1 responses can confer effective antitumor immunity to restrain tumor growth is not well studied. Here, we developed a heterologous prime-boost vaccination strategy to effectively induce tumor-specific TH1 cells and evaluated its antitumor efficacy and its capacity to potentiate PD-1/PD-L1 immunotherapy.MethodsListeria monocytogenes vector and influenza A virus (PR8 strain) vector stably expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein-specific I-Ab-restricted CD4+ T cell epitope (GP61–80) or ovalbumin-specific CD4+ T cell epitope (OVA323-339) were constructed and evaluated their efficacy against mouse models of melanoma and colorectal adenocarcinoma expressing lymphocytic choriomeningitis virus glycoprotein and ovalbumin. The impact of CD4+ T cell epitope-based heterologous prime-boost vaccination was detected by flow-cytometer, single-cell RNA sequencing and single-cell TCR sequencing.ResultsCD4+ T cell epitope-based heterologous prime-boost vaccination efficiently suppressed both mouse melanoma and colorectal adenocarcinoma. This vaccination primarily induced tumor-specific TH1 response, which in turn enhanced the expansion, effector function and clonal breadth of tumor-specific CD8+ T cells. Furthermore, this vaccination strategy synergized PD-L1 blockade mediated tumor suppression. Notably, prime-boost vaccination extended the duration of PD-L1 blockade induced antitumor effects by preventing the re-exhaustion of tumor-specific CD8+ T cells.ConclusionCD4+ T cell epitope-based heterologous prime-boost vaccination elicited potent both tumor-specific TH1 and CTL response, leading to the efficient tumor control. This strategy can also potentiate PD-1/PD-L1 immune checkpoint blockade (ICB) against cancer.

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de Alencar, Bruna C. G., Pedro M. Persechini, Filipe A. Haolla, Gabriel de Oliveira, Jaline C. Silverio, Joseli Lannes-Vieira, Alexandre V. Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, and Mauricio M. Rodrigues. "Perforin and Gamma Interferon Expression Are Required for CD4+ and CD8+ T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination." Infection and Immunity 77, no. 10 (August 3, 2009): 4383–95. http://dx.doi.org/10.1128/iai.01459-08.

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ABSTRACT A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4+ and CD8+ T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4+ and CD8+ T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-γ) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8+ T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-γ or IFN-γ/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-γ in the presence of highly cytotoxic T cells. Vaccinated IFN-γ-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-γ in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.

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Lemckert, Angelique A. C., Shawn M. Sumida, Lennart Holterman, Ronald Vogels, Diana M. Truitt, Diana M. Lynch, Anjali Nanda, et al. "Immunogenicity of Heterologous Prime-Boost Regimens Involving Recombinant Adenovirus Serotype 11 (Ad11) and Ad35 Vaccine Vectors in the Presence of Anti-Ad5 Immunity." Journal of Virology 79, no. 15 (August 1, 2005): 9694–701. http://dx.doi.org/10.1128/jvi.79.15.9694-9701.2005.

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ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.

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Tenbusch, Matthias, Sofie Schumacher, Emanuel Vogel, Alina Priller, Jürgen Held, Philipp Steininger, Stephanie Beileke, et al. "Heterologous prime–boost vaccination with ChAdOx1 nCoV-19 and BNT162b2." Lancet Infectious Diseases 21, no. 9 (September 2021): 1212–13. http://dx.doi.org/10.1016/s1473-3099(21)00420-5.

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Ikeno, Daisuke, Kazuhiko Kimachi, Yasuhiro Kudo, Shuro Goto, Shigeyuki Itamura, Takato Odagiri, Masato Tashiro, and Yoichiro Kino. "A prime–boost vaccination of mice with heterologous H5N1 strains." Vaccine 27, no. 23 (May 2009): 3121–25. http://dx.doi.org/10.1016/j.vaccine.2009.01.007.

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Rühl, Julia, Carmen Citterio, Christine Engelmann, Tracey Haigh, Andrzej Dzionek, Johannes Dreyer, Rajiv Khanna, et al. "Heterologous prime-boost vaccination protects against EBV antigen–expressing lymphomas." Journal of Clinical Investigation 129, no. 5 (April 15, 2019): 2071–87. http://dx.doi.org/10.1172/jci125364.

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Liu, Jinyan, Bonnie A. Ewald, Diana M. Lynch, Matthew Denholtz, Peter Abbink, Angelique A. C. Lemckert, Angela Carville, et al. "Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys." Journal of Virology 82, no. 10 (March 12, 2008): 4844–52. http://dx.doi.org/10.1128/jvi.02616-07.

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ABSTRACT Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-γ+) and IFN-γ+/tumor necrosis factor alpha+ (TNF-α+) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2+ (IL-2+) and polyfunctional IFN-γ+/TNF-α+/IL-2+ T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.

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Meurisse, Marjan, Lucy Catteau, Joris A. F. van Loenhout, Toon Braeye, Laurane De Mot, Ben Serrien, Koen Blot, et al. "Homologous and Heterologous Prime-Boost Vaccination: Impact on Clinical Severity of SARS-CoV-2 Omicron Infection among Hospitalized COVID-19 Patients in Belgium." Vaccines 11, no. 2 (February 7, 2023): 378. http://dx.doi.org/10.3390/vaccines11020378.

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We investigated effectiveness of (1) mRNA booster vaccination versus primary vaccination only and (2) heterologous (viral vector–mRNA) versus homologous (mRNA–mRNA) prime-boost vaccination against severe outcomes of BA.1, BA.2, BA.4 or BA.5 Omicron infection (confirmed by whole genome sequencing) among hospitalized COVID-19 patients using observational data from national COVID-19 registries. In addition, it was investigated whether the difference between the heterologous and homologous prime-boost vaccination was homogenous across Omicron sub-lineages. Regression standardization (parametric g-formula) was used to estimate counterfactual risks for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality under exposure to different vaccination schedules. The estimated risk for severe COVID-19 and in-hospital mortality was significantly lower with an mRNA booster vaccination as compared to only a primary vaccination schedule (RR = 0.59 [0.33; 0.85] and RR = 0.47 [0.15; 0.79], respectively). No significance difference was observed in the estimated risk for severe COVID-19, ICU admission and in-hospital mortality with a heterologous compared to a homologous prime-boost vaccination schedule, and this difference was not significantly modified by the Omicron sub-lineage. Our results support evidence that mRNA booster vaccination reduced the risk of severe COVID-19 disease during the Omicron-predominant period.

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Dangi, Tanushree, Nicole Palacio, Sarah Sanchez, Mincheol Park, Jacob Class, Lavanya Visvabharathy, Thomas Ciucci, Igor J. Koralnik, Justin Richner, and Pablo Penaloza Macmaster. "Cross-protection by SARS vaccines is improved by booster vaccination." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 125.21. http://dx.doi.org/10.4049/jimmunol.208.supp.125.21.

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Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have shown extraordinary efficacy against SARS-CoV-2. Recently, we demonstrated that prime-boost coronavirus vaccine regimens can protect against heterologous coronaviruses (Dangi, The Journal of Clinical Investigation, 2021). However, it remains unclear whether boosters are required for such cross-protection. In this study, we show that booster immunizations are critical to elicit cross-protection against heterologous coronaviruses. We first vaccinated BALB/c mice intramuscularly with a poxvirus-based SARS-CoV-1 vaccine developed in 2004 (MVA-SARS-CoV-1) and compared cross-protection following an intranasal SARS-CoV-2 challenge, evaluating cross-protection after a prime-only regimen versus a prime-boost regimen. Interestingly, we show cross-protection only in mice that received boosters. We are currently testing the durability of cross-protection elicited by prime-boost vaccine regimens, and we are also extending these results to humans. Overall, our findings provide a rationale for universal coronavirus vaccines, and highlights the importance of boosters as a strategy to broaden cross-protection to other coronaviruses different than SARS-CoV-2. Supported by NIDA DP2 Avenir (1DP2DA051912-01) EREEP Grant Northwestern University

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Gola, Anita, Adam A. Walters, Stefan Uderhardt, Ahmed M. Salman, Benedict R. Halbroth, Shahid M. Khan, Chris J. Janse, Ronald N. Germain, Alexandra J. Spencer, and Adrian VS Hill. "Prime and Target Immunization Protects Against Liver-Stage Malaria." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 199.13. http://dx.doi.org/10.4049/jimmunol.198.supp.199.13.

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Abstract A highly effective vaccine against malaria is urgently needed, with leading vaccination strategies targeting primarily the pre-erythrocytic liver stages of the Plasmodium falciparum lifecycle. Malaria antigen specific CD8+ T-cells to are known to be protective, with heterologous prime-boost viral vector immunization being an effective method of induction. Non-replicating viral vectored vaccines have shown a remarkable capacity to induce systemic CD8+ T-cell responses in animals and humans. To date, the greatest immunogenicity has been obtained through a heterologous prime boost regimen, where vaccination with an adenoviral vector is followed 8 weeks later by a Modified Vaccinia Ankara virus (MVA) boost. A novel vaccine strategy aimed at priming CD8+ T-cells in the periphery and subsequently targeting them to hepatic tissue with protein loaded poly(lactic-co-glycolic acid) nanoparticles or recombinant viral vectors administered by specific immunization routes was developed. Durable Ag-specific CD8+ T-cells exhibiting a phenotype of tissue-resident memory (TRM) T-cells were generated in the liver, with a ten-fold increase over the conventional heterologous vector regime. Importantly, in a P. berghei sporozoite challenge model of liver-stage malaria, this strategy was found to result in unprecedented sterile protection across several clinically relevant antigens and mouse strains. This prime and target immunization strategy for malaria may provide a general approach for prevention or immunotherapy against pathogens that infect the liver.

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Suphanchaimat, Rapeepong, Natthaprang Nittayasoot, Chuleeporn Jiraphongsa, Panithee Thammawijaya, Punsapach Bumrungwong, Atthavit Tulyathan, Nontawit Cheewaruangroj, Chakkarat Pittayawonganon, and Piyanit Tharmaphornpilas. "Real-World Effectiveness of Mix-and-Match Vaccine Regimens against SARS-CoV-2 Delta Variant in Thailand: A Nationwide Test-Negative Matched Case-Control Study." Vaccines 10, no. 7 (July 5, 2022): 1080. http://dx.doi.org/10.3390/vaccines10071080.

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The objective of this study is to explore the real-world effectiveness of various vaccine regimens to tackle the epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant in Thailand during September–December 2021. We applied a test-negative case control study, using nationwide records of people tested for SARS-CoV-2. Each case was matched with two controls with respect to age, detection date, and specimen collection site. A conditional logistic regression was performed. Results were presented in the form vaccine effectiveness (VE) and 95% confidence interval. A total of 1,460,458 observations were analyzed. Overall, the two-dose heterologous prime-boost, ChAdOx1 + BNT162b2 and CoronaVac + BNT162b2, manifested the largest protection level (79.9% (74.0–84.5%) and 74.7% (62.8–82.8%)) and remained stable over the whole study course. The three-dose schedules (CoronaVac + CoronaVac + ChAdOx1, and CoronaVac + CoronaVac + BNT162b2) expressed very high degree of VE estimate (above 80.0% at any time interval). Concerning severe infection, almost all regimens displayed very high VE estimate. For the two-dose schedules, heterologous prime-boost regimens seemed to have slightly better protection for severe infection relative to homologous regimens. Campaigns to expedite the rollout of third-dose booster shot should be carried out. Heterologous prime-boost regimens should be considered as an option to enhance protection for the entire population.

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Müller-Hilke, Brigitte, Franz Mai, Michael Müller, Johann Volzke, and Emil C. Reisinger. "Higher SARS-CoV-2 Spike Binding Antibody Levels and Neutralization Capacity 6 Months after Heterologous Vaccination with AZD1222 and BNT162b2." Vaccines 10, no. 2 (February 17, 2022): 322. http://dx.doi.org/10.3390/vaccines10020322.

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Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3–4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections.

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Thorner, Anna R., Angelique A. C. Lemckert, Jaap Goudsmit, Diana M. Lynch, Bonnie A. Ewald, Matthew Denholtz, Menzo J. E. Havenga, and Dan H. Barouch. "Immunogenicity of Heterologous Recombinant Adenovirus Prime-Boost Vaccine Regimens Is Enhanced by Circumventing Vector Cross-Reactivity." Journal of Virology 80, no. 24 (October 11, 2006): 12009–16. http://dx.doi.org/10.1128/jvi.01749-06.

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ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have been constructed from Ad subgroup B, including rAd11 and rAd35, as well as from Ad subgroup D, including rAd49. However, the optimal combination of vectors for heterologous rAd prime-boost vaccine regimens and the extent of cross-reactive vector-specific neutralizing antibodies (NAbs) remain poorly defined. We have shown previously that the closely related vectors rAd11 and rAd35 elicited low levels of cross-reactive NAbs. Here we show that these cross-reactive NAbs correlated with substantial sequence homology in the hexon hypervariable regions (HVRs) and suppressed the immunogenicity of heterologous rAd prime-boost regimens. In contrast, vectors with lower hexon HVR homology, such as rAd35 and rAd49, did not elicit detectable cross-reactive vector-specific NAbs. Consistent with these findings, rAd35-rAd49 vaccine regimens proved more immunogenic than both rAd35-rAd5 and rAd35-rAd11 regimens in mice with anti-Ad5 immunity. These data suggest that optimal heterologous rAd prime-boost regimens should include two vectors that are both rare in human populations to circumvent preexisting antivector immunity as well as sufficiently immunologically distinct to avoid cross-reactive antivector immunity.

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Kim, Dong-In, Seo Jin Lee, Soonju Park, Paul Kim, Sun Min Lee, Nakyung Lee, David Shum, Dong Ho Kim, and Eui Ho Kim. "Immunogenicity and Durability of Antibody Responses to Homologous and Heterologous Vaccinations with BNT162b2 and ChAdOx1 Vaccines for COVID-19." Vaccines 10, no. 11 (November 4, 2022): 1864. http://dx.doi.org/10.3390/vaccines10111864.

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During the COVID-19 pandemic, vaccines were developed based on various platform technologies and were approved for emergency use. However, the comparative analysis of immunogenicity and durability of vaccine-induced antibody responses depending on vaccine platforms or vaccination regimens has not been thoroughly examined for mRNA- or viral vector-based vaccines. In this study, we assessed spike-binding IgG levels and neutralizing capacity in 66 vaccinated individuals prime-boost immunized either by homologous (BNT162b2-BNT162b2 or ChAdOx1-ChAdOx1) or heterologous (ChAdOx1-BNT162b2) vaccination for six months after the first vaccination. Despite the discrepancy in intervals for the prime-boost vaccination regimen of different COVID-19 vaccines, we found stronger induction and relatively rapid waning of antibody responses by homologous vaccination of the mRNA vaccine, while weaker boost effect and stable maintenance of humoral immune responses were observed in the viral vector vaccine group over 6 months. Heterologous vaccination with ChAdOx1 and BNT162b2 resulted in an effective boost effect with the highest remaining antibody responses at six months post-primary vaccination.

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Ho, Tzu-Chuan, Yi-Ming Arthur Chen, Hung-Pin Chan, Chin-Chuan Chang, Kuo-Pin Chuang, Che-Hsin Lee, Cheng-Hui Yuan, Yu-Chang Tyan, and Ming-Hui Yang. "The Effects of Heterologous Immunization with Prime-Boost COVID-19 Vaccination against SARS-CoV-2." Vaccines 9, no. 10 (October 11, 2021): 1163. http://dx.doi.org/10.3390/vaccines9101163.

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Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the global challenge. Reaching global herd immunity will help end the COVID-19 pandemic. However, vaccine shortage and vaccine hesitancy are the obstacles to achieve global herd immunity against SARS-CoV-2. The current homologous vaccine regimen is experimentally switching to heterologous vaccination at several study sites. However, the reactogenicity of heterologous ChAdOx1-S and mRNA vaccination against SARS-CoV-2 is still unclear. We have conducted a systematic review to summarize the current findings on the safety and immunogenicity of this heterologous vaccination and elucidate their implications against SARS-CoV-2. This systematic review was conducted by the guidelines of PRISMA. Articles were searched from PubMed and other sources (MedRixv and Google scholar) starting from 1 January to 5 September 2021. The search term was heterologous ChAdOx1-S and BNT162b2 or mRNA-1273 vaccination. Our review found that participants with ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S did not have the serious adverse events seen with homologous vaccination. Participants with the heterologous regimen (ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S), compared with those with two doses of ChAdOx1-S, have shown a more robust immune responses against SARS-CoV-2, such as higher levels of responsive antibodies or increased numbers of spike-specific T-cells. Nevertheless, these immune responses were slightly diminished in the recipients of BNT162b2/ChAdOx1-S. Also, the safety study of heterologous ChAdOx1-S/mRNA vaccination was based on small populations. Further studies to enclose diverse categories, such as race/ethnicity or geography, may be necessary. Overall, the heterologous immunization with ChAdOX1-S and the mRNA vaccine may improve the vaccine shortage related slow pace of reaching herd immunity, especially using the heterologous immunization with ChAdOx1-S/BNT162b2.

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Mollenkopf, Hans Joachim, Leander Grode, Jens Mattow, Maik Stein, Peggy Mann, Bernhard Knapp, Jeffrey Ulmer, and Stefan H. E. Kaufmann. "Application of Mycobacterial Proteomics to Vaccine Design: Improved Protection by Mycobacterium bovis BCG Prime-Rv3407 DNA Boost Vaccination against Tuberculosis." Infection and Immunity 72, no. 11 (November 2004): 6471–79. http://dx.doi.org/10.1128/iai.72.11.6471-6479.2004.

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ABSTRACT Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost “on top” of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone.

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Parys, Anna, Elien Vandoorn, Koen Chiers, Katharina Passvogel, Walter Fuchs, Thomas C. Mettenleiter, and Kristien Van Reeth. "Exploring Prime-Boost Vaccination Regimens with Different H1N1 Swine Influenza A Virus Strains and Vaccine Platforms." Vaccines 10, no. 11 (October 29, 2022): 1826. http://dx.doi.org/10.3390/vaccines10111826.

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In a previous vaccination study in pigs, heterologous prime-boost vaccination with whole-inactivated H1N1 virus vaccines (WIV) induced superior antibody responses and protection compared to homologous prime-boost vaccination. However, no pan-H1 antibody response was induced. Therefore, to stimulate both local and systemic immune responses, we first vaccinated pigs intranasally with a pseudorabies vector vaccine expressing the pH1N1 hemagglutinin (prvCA09) followed by a homologous or heterologous WIV booster vaccine. Homologous and heterologous WIV–WIV vaccinated groups and mock-vaccinated or prvCA09 single-vaccinated pigs served as control groups. Five weeks after the second vaccination, pigs were challenged with a homologous pH1N1 or one of two heterologous H1N2 swine influenza A virus strains. A single prvCA09 vaccination resulted in complete protection against homologous challenge, and vector–WIV vaccinated groups were significantly better protected against heterologous challenge compared to the challenge control group or WIV–WIV vaccinated groups. Furthermore, vector–WIV vaccination resulted in broader hemagglutination inhibition antibody responses compared to WIV–WIV vaccination and higher numbers of antibody-secreting cells in peripheral blood, draining lymph nodes and nasal mucosa. However, even though vector–WIV vaccination induced stronger antibody responses and protection, we still failed to induce a pan-H1 antibody response.

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Xing, Zhou, and Thomas James Charters. "Heterologous boost vaccines for bacillus Calmette–Guérin prime immunization against tuberculosis." Expert Review of Vaccines 6, no. 4 (August 2007): 539–46. http://dx.doi.org/10.1586/14760584.6.4.539.

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Moore, Anne C., and Adrian V. S. Hill. "Progress in DNA-based heterologous prime-boost immunization strategies for malaria." Immunological Reviews 199, no. 1 (June 2004): 126–43. http://dx.doi.org/10.1111/j.0105-2896.2004.00138.x.

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Liu, J., H. Li, M. J. Iampietro, and D. H. Barouch. "Accelerated Heterologous Adenovirus Prime-Boost SIV Vaccine in Neonatal Rhesus Monkeys." Journal of Virology 86, no. 15 (May 16, 2012): 7829–35. http://dx.doi.org/10.1128/jvi.00512-12.

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Schneider, Jorg, Sarah C. Gilbert, Carolyn M. Hannan, Pilar Degano, Eric Prieur, Eric G. Sheu, Magdalena Plebanski, and Adrian V. S. Hill. "Induction of CD8+ T cells using heterologous prime-boost immunisation strategies." Immunological Reviews 170, no. 1 (August 1999): 29–38. http://dx.doi.org/10.1111/j.1600-065x.1999.tb01326.x.

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Santra, Sampa, Yue Sun, Birgit Korioth-Schmitz, Julie Fitzgerald, Cherie Charbonneau, Giannina Santos, Michael S. Seaman, et al. "Heterologous prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors." Vaccine 27, no. 42 (September 2009): 5837–45. http://dx.doi.org/10.1016/j.vaccine.2009.07.050.

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Abel, Kristina, Lisa Strelow, Yujuan Yue, Meghan K. Eberhardt, Kimberli A. Schmidt, and Peter A. Barry. "A heterologous DNA prime/protein boost immunization strategy for rhesus cytomegalovirus." Vaccine 26, no. 47 (November 2008): 6013–25. http://dx.doi.org/10.1016/j.vaccine.2008.07.103.

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He, Ran. "Efficient control of chronic LCMV infection by CD4 T cell epitope-based heterologous prime-boost vaccination in a murine model." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 123.10. http://dx.doi.org/10.4049/jimmunol.198.supp.123.10.

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Abstract CD4+ T cells are essential for sustaining CD8+ T cell responses during chronic infection. The adoptive transfer of virus-specific CD4+ T cells has been shown to efficiently rescue exhausted CD8+ T cells. However, the question of whether endogenous virus-specific CD4+ T cell responses can be enhanced by certain vaccination strategies and subsequently reinvigorate exhausted CD8+ T cells remains unexplored. In this study, we developed a CD4+ T cell epitope-based heterologous prime-boost immunization strategy and examined the efficacy of this strategy using a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. We primed chronically LCMV-infected mice with the Listeria monocytogenes vector expressing the LCMV glycoprotein-specific I-Ab-restricted CD4+ T cell epitope GP61-80 (LM-GP61) and subsequently boosted the primed mice with an influenza virus A (PR8 strain) vector expressing the same CD4+ T cell epitope (IAV-GP61). This heterologous prime-boost vaccination strategy elicited strong anti-viral CD4+ T cell responses, which further improved both the quantity and quality of the virus-specific CD8+ T cells and led to better control of viral loads. The combination of this strategy and the blockade of the programmed cell death-1 (PD-1) inhibitory pathway further enhanced anti-viral CD8+ T cell responses and viral clearance. Therefore, heterologous prime-boost immunization that selectively induces virus-specific CD4+ T cell responses in conjunction with inhibitory pathway blockade may represent a promising therapeutic approach to treating patients with chronic viral infection.

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Michiels, Yves, Nadhira Houhou-Fidouh, Gilles Collin, Jérôme Berger, and Evelyne Kohli. "Humoral Response Induced by Prime-Boost Vaccination with the ChAdOx1 nCoV-19 and mRNA BNT162b2 Vaccines in a Teriflunomide-Treated Multiple Sclerosis Patient." Vaccines 9, no. 10 (October 6, 2021): 1140. http://dx.doi.org/10.3390/vaccines9101140.

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Patients with multiple sclerosis (MS) are treated with drugs that may impact immune responses to SARS-CoV-2 vaccination. Evaluation of “prime-boost” (heterologous) vaccination regimens including a first administration of a viral vector-based vaccine and a second one of an mRNA-based vaccine in such patients has not yet been completed. Here, we present the anti-spike protein S humoral response, including the neutralizing antibody response, in a 54-year-old MS patient who had been treated with teriflunomide for the past 2 years and who received a heterologous ChAdOx1 nCoV-19/ BNT162b2 vaccination regimen. The results showed a very strong anti-S IgG response and a good neutralizing antibody response. These results show that teriflunomide did not prevent the development of a satisfactory humoral response in this MS patient after vaccination with a ChAdOx1 nCoV-19/ BNT162b2 prime-boost protocol.

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Raposo, Francisco, and Giuseppe Lippi. "Antibody response induced by the boost overdose during COVID-19 heterologous prime-boost vaccination strategy." Clinica Chimica Acta 523 (December 2021): 201–4. http://dx.doi.org/10.1016/j.cca.2021.09.022.

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Kim, Jaejo, Seung-Heon Lee, Ha-Hyun Kim, Jong-Hyeon Park, and Choi-Kyu Park. "Heterologous Prime-Boost Vaccination with Commercial FMD Vaccines Elicits a Broader Immune Response than Homologous Prime-Boost Vaccination in Pigs." Vaccines 11, no. 3 (February 25, 2023): 551. http://dx.doi.org/10.3390/vaccines11030551.

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Three commercial vaccines are administered in domestic livestock farms for routine vaccination to aid for foot-and-mouth disease (FMD) control in Korea. Each vaccine contains distinct combinations of inactivated serotype O and A FMD virus (FMDV) antigens: O/Manisa + O/3039 + A/Iraq formulated in a double oil emulsion (DOE), O/Primorsky + A/Zabaikalsky formulated in a DOE, and O/Campos + A/Cruzeiro + A/2001 formulated in a single oil emulsion. Despite the recommendation for a prime-boost vaccination with the same vaccine in fattening pigs, occasional cross-inoculation is inevitable for many reasons, such as lack of compliance with vaccination guidelines, erroneous application, or change in vaccine types by suppliers. Therefore, there have been concerns that a poor immune response could be induced by cross-inoculation due to a failure to boost the immune response. In the present study, it was demonstrated by virus neutralization and ELISA tests that cross-inoculation of pigs with three commercial FMD vaccines does not hamper the immune response against the primary vaccine strains and enhances broader cross-reactivity against heterologous vaccine antigens whether they were applied or not. Therefore, it could be concluded that the cross-inoculation of FMD vaccines can be used as a regimen to strategically overcome the limitation of the antigenic spectrum induced by the original regimen.

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Benning, Louise, Maximilian Töllner, Asa Hidmark, Matthias Schaier, Christian Nusshag, Florian Kälble, Paula Reichel, et al. "Heterologous ChAdOx1 nCoV-19/BNT162b2 Prime-Boost Vaccination Induces Strong Humoral Responses among Health Care Workers." Vaccines 9, no. 8 (August 4, 2021): 857. http://dx.doi.org/10.3390/vaccines9080857.

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Despite limited data on safety and immunogenicity, heterologous prime-boost vaccination is currently recommended for individuals with ChAdOx1 nCoV-19 prime immunization in certain age groups. In this prospective, single-center study we included 166 health care workers from Heidelberg University Hospital who received either heterologous ChAdOx1 nCoV-19/BNT162b2, homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination between December 2020 and May 2021. We measured anti-S1 IgG, SARS-CoV-2 specific neutralizing antibodies, and antibodies against different SARS-CoV-2 fragments 0–3 days before and 19–21 days after boost vaccination. Before boost, 55/70 (79%) ChAdOx1 nCoV-19-primed compared with 44/45 (98%) BNT162b2-primed individuals showed positive anti-S1 IgG with a median (IQR) anti-S1 IgG index of 1.95 (1.05–2.99) compared to 9.38 (6.26–17.12). SARS-CoV-2 neutralizing antibodies exceeded the threshold in 24/70 (34%) of ChAdOx1 nCoV-19-primed and 43/45 (96%) of BNT162b2-primed individuals. After boosting dose, median (IQR) anti-S1 IgG index in heterologous ChAdOx1 nCoV-19/BNT162b2 vaccinees was 116.2 (61.84–170), compared to 13.09 (7.03–29.02) in homologous ChAdOx1 nCoV-19 and 145.5 (100–291.1) in homologous BNT162b2 vaccinees. All boosted vaccinees exceeded the threshold for neutralization, irrespective of their vaccination scheme. Vaccination was well-tolerated overall. We show that heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination is safe and induces a strong and broad humoral response in healthy individuals.

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Hovav, Avi-Hai, Mark J. Cayabyab, Michael W. Panas, Sampa Santra, John Greenland, Ralf Geiben, Barton F. Haynes, William R. Jacobs, and Norman L. Letvin. "Rapid Memory CD8+ T-Lymphocyte Induction through Priming with Recombinant Mycobacterium smegmatis." Journal of Virology 81, no. 1 (October 18, 2006): 74–83. http://dx.doi.org/10.1128/jvi.01269-06.

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ABSTRACT The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4+ T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant-mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant-mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8+ T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.

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Barouch, Dan H., Paul F. McKay, Shawn M. Sumida, Sampa Santra, Shawn S. Jackson, Darci A. Gorgone, Michelle A. Lifton, et al. "Plasmid Chemokines and Colony-Stimulating Factors Enhance the Immunogenicity of DNA Priming-Viral Vector Boosting Human Immunodeficiency Virus Type 1 Vaccines." Journal of Virology 77, no. 16 (August 15, 2003): 8729–35. http://dx.doi.org/10.1128/jvi.77.16.8729-8735.2003.

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ABSTRACT Heterologous “prime-boost” regimens that involve priming with plasmid DNA vaccines and boosting with recombinant viral vectors have been shown to elicit potent virus-specific cytotoxic T-lymphocyte responses. Increasing evidence, however, suggests that the utility of recombinant viral vectors in human populations will be significantly limited by preexisting antivector immunity. Here we demonstrate that the coadministration of plasmid chemokines and colony-stimulating factors with plasmid DNA vaccines markedly increases the immunogenicity of DNA prime-recombinant adenovirus serotype 5 (rAd5) boost and DNA prime-recombinant vaccinia virus (rVac) boost vaccine regimens in BALB/c mice. In mice with preexisting anti-Ad5 immunity, priming with the DNA vaccine alone followed by rAd5 boosting elicited only marginal immune responses. In contrast, cytokine-augmented DNA vaccine priming followed by rAd5 vector boosting was able to generate potent immune responses in mice with preexisting anti-Ad5 immunity. These data demonstrate that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity.

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Walther, Michael, Fiona M. Thompson, Susanna Dunachie, Sheila Keating, Stephen Todryk, Tamara Berthoud, Laura Andrews, et al. "Safety, Immunogenicity, and Efficacy of Prime-Boost Immunization with Recombinant Poxvirus FP9 and Modified Vaccinia Virus Ankara Encoding the Full-Length Plasmodium falciparum Circumsporozoite Protein." Infection and Immunity 74, no. 5 (May 2006): 2706–16. http://dx.doi.org/10.1128/iai.74.5.2706-2716.2006.

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ABSTRACT Heterologous prime-boost immunization with DNA and various recombinant poxviruses encoding malaria antigens is capable of inducing strong cell-mediated immune responses and partial protection in human sporozoite challenges. Here we report a series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes. For the first time, these vaccines were administered intramuscularly and at doses of up to 5 × 108 PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.

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Orlinger, Klaus Karl, Weldy V. Bonilla, Sandra M. Kallert, Nicole Kirchhammer, Anna-Friederike Marx, Magdalena Krzyzaniak, Sarah Schmidt, et al. "Arenavirus-based vector platform for massive tumor self-antigen-specific CD8 T cell immunity." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14297-e14297. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14297.

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e14297 Background: The induction of powerful CD8+ T cell immunity to tumor associated self-antigens (TAAs) represents a critical yet challenging goal. Here we report on the development of an arenavirus-based delivery platform meeting this challenge. Previously we have shown that genetically engineered replication-attenuated lymphocytic choriomeningitis virus (LCMV) vectors, TheraT(LCMV), induce strong TAA-specific CD8 T cell immunity, but these responses can not be substantially augmented upon TheraT(LCMV) readministration. Counter to expectations, vector-neutralizing antibodies were not accountable for limited homologous prime-boosting capacity. Instead, dominant viral backbone-reactive CD8+ T cells competed against subdominant TAA-specific responses, limiting their magnitude. Methods: Herein we engineered and characterized delivery systems based on the arenaviruses Mopeia, Candid#1 and Pichinde (TheraT(MOP), TheraT(CAND), TheraT(PIC)). Results: We demonstrate that heterologous TheraT(CAND) – TheraT(LCMV) and TheraT(PIC)-TheraT(LCMV) prime-boost substantially augment TAA-specific CD8 T cell responses by rendering them immunodominant. Accordingly, intravenous administration of mice triggered up to 50% TAA epitope-specific CD8+ T cells and cured established tumors. Conversely, TheraT(MOP) – TheraT(LCMV) prime-boost was poorly immunogenic owing to cross-reactive T cell epitopes in the respective viral backbones. Conclusions: These findings establish heterologous arenavirus prime-boost combinations as a powerful new modality in tumor immunotherapy and highlight CD8 T cell epitope dominance as a significant hurdle to overcome in the vectored delivery of TAAs.

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Kim, Silvia, Jeffrey Currier, Josephine Cox, Jean-Louis Excler, Eddy Sayeed, Merlin Robb, Jerome Kim, Nelson Michael, and Mary Marovich. "Cellular immunogenicity of an Ad35GGRIN+ENV and MVA-CMDR prime-boost vaccine regimen. (42.3)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 42.3. http://dx.doi.org/10.4049/jimmunol.184.supp.42.3.

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Abstract Newer HIV-1 vaccine strategies use heterologous prime-boost regimens to stimulate broader immune responses. We tested 2 heterologous vectors with heterologous HIV-1 gene inserts: Ad35GRIN+Ad35ENV and MVA-CMDR. The Ad35GRIN+Ad35ENV vaccine is comprised of two vectors containing sequences from HIV-1 subtype A (GRIN=gag, rt, int and nef and ENV=env). MVA-CMDR contains genes from HIV-1 subtype CRF01_AE (gag, env and pol). Balb/c mice (5/group) were immunized according to the following schema: Group 1:MVA-CMDR-MVA-CMDR; Group 2:MVA-CMDR-Ad35GRIN+ENV; Group 3:Ad35GRIN+ENV-MVA-CMDR; Group 4:Ad35GRIN+ENV-Ad35GRIN+ENV. Immunogenicity testing was performed at 2 weeks post boost: ELISPOT, ICS (CD107a, IFNγ, TNFα and IL-2) and pentamer (H-2Kd) Gag epitope staining were used. A variety of stimuli were used to define responses to inserts and vectors. Insert-specific immune responses were detected in all groups. The best combination was Group 3. Notably, there was a shift from a focused vector response in Group 1 to an insert response in Group 3 (0.78% CD8+INFγ gag pool response and 4.24% CD8+INFγ MVA response in Group 1 vs 5.74% CD8+INFγ gag pool response and 0.61% CD8+INFγ MVA response in Group 3). The relative contributions of vector versus insert are not clear. It appears that the insert response is dominant in the heterologous vector format and that subtle differences in cross-reactive populations can be revealed using the pentamer (H-2Kd) Gag epitope staining.

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Sabarth, Nicolas, M. Keith Howard, Helga Savidis-Dacho, André van Maurik, P. Noel Barrett, and Otfried Kistner. "Comparison of single, homologous prime-boost and heterologous prime-boost immunization strategies against H5N1 influenza virus in a mouse challenge model." Vaccine 28, no. 3 (January 2010): 650–56. http://dx.doi.org/10.1016/j.vaccine.2009.10.105.

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Valdés, Iris, Lázaro Gil, Yaremis Romero, Jorge Castro, Pedro Puente, Laura Lazo, Ernesto Marcos, María G. Guzmán, Gerardo Guillén, and Lisset Hermida. "The Chimeric Protein Domain III-Capsid of Dengue Virus Serotype 2 (DEN-2) Successfully Boosts Neutralizing Antibodies Generated in Monkeys upon Infection with DEN-2." Clinical and Vaccine Immunology 18, no. 3 (January 5, 2011): 455–59. http://dx.doi.org/10.1128/cvi.00382-10.

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ABSTRACTUse of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time spacing. The present work deals with the evaluation of the heterologous prime-boost strategy combining a novel chimeric protein (domain III-capsid) of dengue virus serotype 2 (DEN-2) and the infective homologous virus in the same immunization schedule in monkeys. Primed monkeys received one dose of infective DEN-2 and were then vaccinated with the recombinant protein. We found that animals developed a neutralizing antibody response after the infective dose and were notably boosted with a second dose of the chimeric protein 3 months later. The neutralizing antibodies induced were long lasting, and animals also showed the ability to induce a specific cellular response 6 months after the booster dose. As a conclusion, we can state that the domain III region, when it is properly presented as a fusion protein to the immune system, is able to recall the neutralizing antibody response elicited following homologous virus infection in monkeys. Further prime-boost approaches can be performed in a condensed regime combining the chimeric domain III-capsid protein and candidate live attenuated vaccines against DEN-2.

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Fiander, A. N., A. J. Tristram, E. J. Davidson, A. E. Tomlinson, S. Man, P. J. Baldwin, J. C. Sterling, and H. C. Kitchener. "Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial." International Journal of Gynecologic Cancer 16, no. 3 (2006): 1075–81. http://dx.doi.org/10.1136/ijgc-00009577-200605000-00020.

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The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

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