Impact of antibody quality and anamnestic response on viremia control post-challenge in a combined Tat/Env vaccine regimen in rhesus macaques.

Published

Journal Article

Previously, priming rhesus macaques with Adenovirus type 5 host range mutant-recombinants encoding Tat and Env and boosting with Tat and Env protein in MPL-SE controlled chronic viremia by 4 logs following homologous intravenous SHIV89.6P challenge. Here we evaluated Tat, Env, and Tat/Env regimens for immunogenicity and protective efficacy using clade C Env, alum adjuvant, and a heterologous intrarectal SHIV1157ipd3N4 challenge. Despite induction of strong cellular and humoral immunity, Tat/Env group T and B-cell memory responses were not significantly enhanced over Tat- or Env-only groups. Lack of viremia control post-challenge was attributed to lower avidity Env antibodies and no anamnestic ADCC response or SHIV1157ipd3N4 neutralizing antibody development post-challenge. Poor biologic activity of the Tat immunogen may have impaired Tat immunity. In the absence of sterilizing immunity, strong anamnestic responses to heterologous virus can help control viremia. Both antibody breadth and optimal adjuvanticity are needed to elicit high-quality antibody for protective efficacy.

Full Text

Duke Authors

Cited Authors

  • Demberg, T; Brocca-Cofano, E; Kuate, S; Aladi, S; Vargas-Inchaustegui, DA; Venzon, D; Kalisz, I; Kalyanaraman, VS; Lee, EM; Pal, R; DiPasquale, J; Ruprecht, RM; Montefiori, DC; Srivastava, I; Barnett, SW; Robert-Guroff, M

Published Date

  • June 5, 2013

Published In

Volume / Issue

  • 440 / 2

Start / End Page

  • 210 - 221

PubMed ID

  • 23528732

Pubmed Central ID

  • 23528732

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2013.02.024

Language

  • eng

Conference Location

  • United States