HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site

PLoS One. 2017 Oct 11;12(10):e0177863. doi: 10.1371/journal.pone.0177863. eCollection 2017.

Abstract

Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibody Formation / immunology
  • Binding Sites
  • CD4 Antigens / metabolism*
  • Female
  • HEK293 Cells
  • HIV Antigens / immunology
  • HIV Infections / immunology*
  • HIV Infections / transmission*
  • Humans
  • Macaca mulatta
  • Vaccines, DNA / immunology
  • Vaccinia virus / immunology
  • Vaccinia virus / ultrastructure
  • env Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • CD4 Antigens
  • HIV Antigens
  • Vaccines, DNA
  • env Gene Products, Human Immunodeficiency Virus