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

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Item Type:Article
Title:HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
Creators Name:Capucci, S., Wee, E.G., Schiffner, T., LaBranche, C.C., Borthwick, N., Cupo, A., Dodd, J., Dean, H., Sattentau, Q., Montefiori, D., Klasse, P.J., Sanders, R.W., Moore, J.P. and Hanke, T.
Abstract: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 ISCOMATRIX™–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.
Keywords:AIDS Vaccines, Cell Line, DNA Vaccines, HEK293 Cells, HIV Antibodies, HIV-1, Human Immunodeficiency Virus env Gene Products, Neutralizing Antibodies, Protein Multimerization, Simian Adenoviruses, Vaccination, Vaccinia virus, Viral Vaccines, Animals, Rabbits
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:12
Number:8
Page Range:e0181886
Date:9 August 2017
Additional Information:Erratum in: PLoS ONE 18(10): e0293148.
Official Publication:https://doi.org/10.1371/journal.pone.0181886
PubMed:View item in PubMed

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