Therapeutic vaccination following early antiretroviral therapy elicits highly functional T cell responses against conserved HIV-1 regions

Abstract

Abstract‘Kick and kill’ cure strategies aim to induce HIV protein expression in latently infected cells (kick), and thus trigger their elimination by cytolytic T cells (kill). In the Research in Viral Eradication of HIV Reservoirs trial (NCT02336074), people diagnosed with primary HIV infection received immediate antiretroviral therapy (ART) and were randomised 24 weeks later to either a latency-reversing agent, vorinostat, together with ChAdV63.HIVconsv and MVA.HIVconsv vaccines, or ART alone. This intervention conferred no reduction in HIV-1 reservoir size over ART alone, despite boosting virus-specific CD4+ and CD8+ T cells. The effects of the intervention were examined at the cellular level in the two trial arms using unbiased computational analysis of polyfunctional scores. This showed that the frequency and polyfunctionality of virus-specific CD4+ and CD8+ T cell populations were significantly increased over 12 weeks post-vaccination, compared to the ART-only arm. HIV-specific IL-2-secreting CD8+ T cells also expanded significantly in the intervention arm and were correlated with antiviral activity against heterologous HIV in vitro. Therapeutic vaccination during ART commenced in primary infection can induce functional T cell responses that are phenotypically similar to those of HIV controllers. Analytical therapy interruption may help determine their ability to control HIV in vivo.

Impact of Recombinant VSV-HIV Prime, DNA-Boost Vaccine Candidates on Immunogenicity and Viremia on SHIV-Infected Rhesus Macaques

“…In contrast, Group A74 exhibited neither of these trends in proliferation or CD154, instead displaying patterns similar to, if not lower than, the experimental controls, yet a larger percentage of animals (50%) endured the first round of challenge compared to the controls (20%). The implications of these and other cell-mediated forms of immunity should be investigated as in previous research [53,54].…”

Strategies to target the central nervous system HIV reservoir

“…On the contrary, a more recent study failed to detect anti-SIV edited cells in the brain of macaques with SIV infection [65 ▪▪ ]. In addition, very limited data on the penetration and effectiveness in the CNS of anti-HIV T-cells elicited after therapeutic vaccination are available to date, and focusing on these aspects may be warranted in the future trials [66,67,68 ▪ ,69 ▪ ].…”