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

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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… Click to show full abstract

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: first generation; generation conserved; conserved region; clinical trials; preventive therapeutic; therapeutic clinical

Journal Title: Expert Review of Vaccines
Year Published: 2019

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