HIV Vaccines: Bridging the Gap Between Basic Science and Clinical Practice

Dear Colleagues,

It has been more than 40 years since the initial report on AIDS in the United States (1) and the identification of human immunodeficiency virus type 1 (HIV) as the causative agent subsequently (2,3). Unfortunately, the majority of large-scale human efficacy clinical trials evaluating HIV vaccine candidates over the past three decades have yielded disappointing outcomes (4–11). Nevertheless, during this period, extensive data on HIV vaccine research, including immunogen discovery and design, vaccine development, and clinical trials, have been generated through funding from public agencies and private foundations. It is widely recognized within this scientific community that true advancements can be achieved through the analysis of past failures and past limited successes.

This Special Issue, HIV Vaccines, aims to stimulate candid discussions and analyses of past failures as well as to inspire innovative ideas and candid debates for future HIV vaccine development, evaluation, and clinical trials. For example, the reasons that HIV vaccines have failed in large clinical trials are complex and multifaceted, including the failure to elicit potent neutralizing antibodies or/and protective cellular immunity, the inability to deal with HIV diversity, or the activation of CD⁴⁺ T cells in mucosal sites. Further, the reason that the vaccines achieved 31% protection in the RV144 trial but failed in the HVTN702 trial is yet to be determined. Additionally, key questions that need revisiting in human clinical trials include the suitability of HIV-specific IFN-γ-secreting T cells for assessing T cell responses, the consideration of host genetic factors, and the effectiveness of using nonhuman primate/SIV models for studying HIV vaccine efficacy. This Special Issue is in search of original studies, reviews, and scientific opinion articles which do not have to be comprehensive but should be backed up with data/evidence either from published studies or the authors’ own studies.

References

1. A Timeline of HIV and AIDS2021.
2. Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983;220(4599):865-7. Epub 1983/05/20.
3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983;220(4599):868-71. Epub 1983/05/20.
4. Bower R. Researchers halt HIV vaccine trial—What's the next step? AIDS Alert. 2008;23(1):8-10. Epub 2008/06/25.
5. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372(9653):1881-93. Epub 2008/11/18.
6. HIV vaccine failure prompts Merck to halt trial. Nature. 2007;449(7161):390. Epub 2007/09/28.
7. Gray GE, Bekker LG, Laher F, Malahleha M, Allen M, Moodie Z et al. Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults. N Engl J Med. 2021;384(12):1089-100. Epub 2021/03/25.
8. Moodie Z, Dintwe O, Sawant S, Grove D, Huang Y, Janes H et al. Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk. J Infect Dis. 2022;226(2):246-57. Epub 2022/06/28.
9. Zolla-Pazner S, Michael NL, Kim JH. A tale of four studies: HIV vaccine immunogenicity and efficacy in clinical trials. The lancet HIV. 2021;8(7):e449-e52. Epub 2021/05/25.
10. Vaccari M, Poonam P, Franchini G. Phase III HIV vaccine trial in Thailand: a step toward a protective vaccine for HIV. Expert Rev Vaccines. 2010;9(9):997-1005. Epub 2010/09/09.
11. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366(14):1275-86. Epub 2012/04/06.

Dr. Ma Luo
Dr. Qingsheng Li
Guest Editors

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• HIV vaccine
• clinical trial
• immunogens
• cellular immunity
• antibody response
• HIV diversity
• NHP models
• host genetic factors