Conserved multiepitope vaccine constructs: A potent HIV-1 therapeutic vaccine in clinical trials

Despite the success of Antiretroviral Therapy (ART) in preventing HIV-1-associated clinical progression to AIDS, it is unable to eliminate the viral reservoirs and eradicate the HIV-1 infection. Therapeutic vaccination is an alternative approach to alter the HIV-1 infection course. It can induce effective HIV-1-specific immunity to control vire-mia and eliminate the need for lifelong ART. Immunological data from spontaneous HIV-1 controllers have shown that cross-reactive T-cell responses are the key immune mechanism in HIV-1 control. Directing these responses toward preferred HIV-1 epito-pes is a promising strategy in therapeutic vaccine settings. Designing novel immuno-gens based on the HIV-1 conserved regions containing a wide range of critical T-and B-cell epitopes of the main viral antigens (conserved multiepitope approaches) sup-plies broad coverage of global diversity in HIV-1 strains and Human Leukocyte Antigen (HLA) alleles. It can also prevent immune induction to undesirable decoy epitopes the-oretically. The efficacy of different novel HIV-1 immunogens based on the conserved and/or functional protective site of HIV-1 proteome has been evaluated in multiple clinical trials. Most of these immunogens were generally safe and able to induce potent HIV-1-specific immunity. However, despite these findings, several candidates have demonstrated limited efficacy in viral replication control. In this study, we used the PubMed and ClinicalTrial.gov databases to review the rationale of designing cura-tive HIV-1 vaccine immunogens based on the conserved favorable site of the virus. Most of these studies evaluate the efficacy of vaccine candidates in combination with other therapeutics and/or with new formulations and immunization protocols. This review briefly describes the design of conserved multiepitope constructs and outlines the results of these vaccine candidates in the recent clinical pipeline.(c) 2023 Sociedade Brasileira de Infectologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

Despite the success of Antiretroviral Therapy (ART) in preventing HIV-1 progression, therapeutic vaccination is being explored as an alternative approach to control the virus and eliminate the need for lifelong ART. By targeting preferred HIV-1 epitopes, novel immunogens can induce broad coverage of global HIV-1 strains and HLA alleles, while preventing immune induction to undesirable epitopes.