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

PLoS One. 2017 Aug 9;12(8):e0181886. doi: 10.1371/journal.pone.0181886. eCollection 2017.

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.

MeSH terms

  • AIDS Vaccines / immunology
  • Adenoviruses, Simian / immunology*
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Cell Line
  • HEK293 Cells
  • HIV Antibodies / immunology*
  • HIV-1 / immunology*
  • Humans
  • Protein Multimerization / immunology
  • Rabbits
  • Vaccination
  • Vaccines, DNA
  • Vaccinia virus / immunology*
  • Viral Vaccines / immunology*
  • env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • MVA vaccine
  • Vaccines, DNA
  • Viral Vaccines
  • env Gene Products, Human Immunodeficiency Virus