HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers

Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s t...

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Main Authors: Capucci, S, Wee, E, Schiffner, T, Labranche, C, Borthwick, N, Cupo, A, Dodd, J, Dean, H, Sattentau, Q, Montefiori, D, Klasse, P, Sanders, R, Moore, J, Hanke, T
Format: Journal article
Published: Public Library of Science 2017
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author Capucci, S
Wee, E
Schiffner, T
Labranche, C
Borthwick, N
Cupo, A
Dodd, J
Dean, H
Sattentau, Q
Montefiori, D
Klasse, P
Sanders, R
Moore, J
Hanke, T
author_facet Capucci, S
Wee, E
Schiffner, T
Labranche, C
Borthwick, N
Cupo, A
Dodd, J
Dean, H
Sattentau, Q
Montefiori, D
Klasse, P
Sanders, R
Moore, J
Hanke, T
author_sort Capucci, S
collection OXFORD
description Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1.BG505s (C) and MVA.BG505s (M) vaccine-infected cells, respectively, were cleaved and in a native-like conformation. Rabbits were immunized intramuscularly with these vaccine vectors and in some cases boosted with ISCOMATRIXTM–adjuvanted BG505s protein trimer (P), using CCC, MMM, PPP, CPP, MPP and CMP vaccine regimens. We found that the peak trimer-binding antibody and tier-1A and autologous tier-2 nAb responses induced by the CC, CM, PPP, CPP, MPP and CMP regimens were comparable, although only PPP induced autologous tier-2 nAbs in all the immunized animals. Three animals developed weak heterologous tier-2 nAbs. These results demonstrate that ChAdOx1 and MVA vectors are useful delivery modalities for not only T-cell, but also antibody, vaccine development.
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spelling oxford-uuid:ad98f002-a408-4077-9b96-15fc2c6e5b062022-03-27T03:36:48ZHIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ad98f002-a408-4077-9b96-15fc2c6e5b06Symplectic Elements at OxfordPublic Library of Science2017Capucci, SWee, ESchiffner, TLabranche, CBorthwick, NCupo, ADodd, JDean, HSattentau, QMontefiori, DKlasse, PSanders, RMoore, JHanke, TRabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1.BG505s (C) and MVA.BG505s (M) vaccine-infected cells, respectively, were cleaved and in a native-like conformation. Rabbits were immunized intramuscularly with these vaccine vectors and in some cases boosted with ISCOMATRIXTM–adjuvanted BG505s protein trimer (P), using CCC, MMM, PPP, CPP, MPP and CMP vaccine regimens. We found that the peak trimer-binding antibody and tier-1A and autologous tier-2 nAb responses induced by the CC, CM, PPP, CPP, MPP and CMP regimens were comparable, although only PPP induced autologous tier-2 nAbs in all the immunized animals. Three animals developed weak heterologous tier-2 nAbs. These results demonstrate that ChAdOx1 and MVA vectors are useful delivery modalities for not only T-cell, but also antibody, vaccine development.
spellingShingle Capucci, S
Wee, E
Schiffner, T
Labranche, C
Borthwick, N
Cupo, A
Dodd, J
Dean, H
Sattentau, Q
Montefiori, D
Klasse, P
Sanders, R
Moore, J
Hanke, T
HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
title HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
title_full HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
title_fullStr HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
title_full_unstemmed HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
title_short HIV-1-neutralizing antibody 1 induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
title_sort hiv 1 neutralizing antibody 1 induced by simian adenovirus and poxvirus mva vectored bg505 native like envelope trimers
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