T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates

Immune responses against multiple epitopes are required for the prevention of Hepatitis C Virus infection, and the progression to Phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Mo...

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Main Authors: Rollier, C, Verschoor, E, Verstrepen, B, Drexhage, J, Paranhos-Baccala, G, Liljeström, P, Sutter, G, Arribillaga, L, Lasarte, J, Bartosch, B, Cosset, F, Inchauspe, G, Heeney, J
Format: Journal article
Published: Nature Publishing Group 2016
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author Rollier, C
Verschoor, E
Verstrepen, B
Drexhage, J
Paranhos-Baccala, G
Liljeström, P
Sutter, G
Arribillaga, L
Lasarte, J
Bartosch, B
Cosset, F
Inchauspe, G
Heeney, J
author_facet Rollier, C
Verschoor, E
Verstrepen, B
Drexhage, J
Paranhos-Baccala, G
Liljeström, P
Sutter, G
Arribillaga, L
Lasarte, J
Bartosch, B
Cosset, F
Inchauspe, G
Heeney, J
author_sort Rollier, C
collection OXFORD
description Immune responses against multiple epitopes are required for the prevention of Hepatitis C Virus infection, and the progression to Phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara poxvirus (MVA), all expressing HCV Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN- production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared to the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared to those receiving MVA. The IFN- responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.
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spelling oxford-uuid:7749c164-6399-4750-8893-8c5d24edfd302022-03-26T20:22:56ZT and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primatesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7749c164-6399-4750-8893-8c5d24edfd30Symplectic Elements at OxfordNature Publishing Group2016Rollier, CVerschoor, EVerstrepen, BDrexhage, JParanhos-Baccala, GLiljeström, PSutter, GArribillaga, LLasarte, JBartosch, BCosset, FInchauspe, GHeeney, JImmune responses against multiple epitopes are required for the prevention of Hepatitis C Virus infection, and the progression to Phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara poxvirus (MVA), all expressing HCV Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN- production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared to the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared to those receiving MVA. The IFN- responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.
spellingShingle Rollier, C
Verschoor, E
Verstrepen, B
Drexhage, J
Paranhos-Baccala, G
Liljeström, P
Sutter, G
Arribillaga, L
Lasarte, J
Bartosch, B
Cosset, F
Inchauspe, G
Heeney, J
T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates
title T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates
title_full T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates
title_fullStr T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates
title_full_unstemmed T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates
title_short T and B cell responses to multivalent prime-boost DNA and viral vectors vaccine combinations against Hepatitis C virus in non-human primates
title_sort t and b cell responses to multivalent prime boost dna and viral vectors vaccine combinations against hepatitis c virus in non human primates
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