Aiming for protective T-cell responses: a focus on the first generation conserved-region HIVconsv vaccines in preventive and therapeutic clinical trials

Expert Rev Vaccines. 2019 Oct;18(10):1029-1041. doi: 10.1080/14760584.2019.1675518. Epub 2019 Oct 15.

Abstract

Introduction: Despite life-saving antiretroviral drugs, an effective HIV-1 vaccine is the best solution and likely a necessary component of any strategy for halting the AIDS epidemic. The currently prevailing aim is to pursue antibody-mediated vaccine protection. With ample evidence for the ability of T cells to control HIV-1 replication, their protective potential should be also harnessed by vaccination. The challenge is to elicit not just any, but protective T cells.Areas covered: This article reviews the clinical experience with the first-generation conserved-region immunogen HIVconsv delivered by combinations of plasmid DNA, simian adenovirus, and poxvirus MVA. The aim of our strategy is to induce strong and broad T cells targeting functionally important parts of HIV-1 proteins common to global variants. These vaccines were tested in eight phase 1/2 preventive and therapeutic clinical trials in Europe and Africa, and induced high frequencies of broadly specific CD8+ T cells capable of in vitro inhibition of four major HIV-1 clades A, B, C and D, and in combination with latency-reactivating agent provided a signal of drug-free virological control in early treated patients.Expert opinion: A number of critical T-cell traits have to come together at the same time to achieve control over HIV-1.

Keywords: HIV cure; HIV vaccines; HIVconsv; MVA; T cells; clinical trials; conserved regions; prime-boost; simian adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIDS Vaccines / immunology*
  • Adenoviruses, Simian
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Clinical Trials as Topic
  • HIV Infections / prevention & control*
  • HIV Infections / therapy*
  • HIV-1 / immunology
  • Humans
  • Plasmids
  • Poxviridae
  • T-Lymphocytes / immunology*
  • Vaccination
  • Vaccines, DNA / immunology
  • Viral Proteins

Substances

  • AIDS Vaccines
  • Vaccines, DNA
  • Viral Proteins