REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Understanding the Performance of HIV-1 Viral Vector Vaccines: Adenovirus and Poxvirus Case Studies
Provisionally accepted
- 1University of Massachusetts Boston, Boston, United States
- 2Broad Institute, Cambridge, MA, United States
- 3Harvard University, Cambridge, United States
- 4Broad Institute, Cambridge, United States
- 5Harvard Medical School, Boston, United States
- 6Boston Children's Hospital, Boston, United States
- 7Howard Hughes Medical Institute, Chevy Chase, United States
- 8Harvard University Department of Organismic & Evolutionary Biology, Cambridge, United States
- 9Harvard T H Chan School of Public Health, Boston, United States
- 10Massachusetts General Hospital, Boston, United States
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Abstract Despite decades of research, HIV-1 continues to infect millions annually, underscoring the urgent need for a safe and effective vaccine to curb the ongoing global pandemic. Among the many strategies explored, viral vectors have been the most intensively studied, with adenoviral and poxviral platforms serving as the leading approaches. These vectors have advanced through extensive preclinical evaluation and multiple large-scale clinical trials, demonstrating safety and the ability to induce cellular and humoral responses. Yet, they have also revealed key challenges, including pre-existing vector immunity, limited durability of responses, and in some cases, increased susceptibility to infection. Importantly, these trials clarified the limitations of Env-focused immunity, highlighted the value of heterologous prime–boost regimens, and reinforced the dual need for broadly neutralizing antibodies and functional T cell responses. While vector-based COVID vaccines achieved protective efficacy, lessons learned from adenoviral and poxviral efforts continue to shape the field, directly informing the design of next-generation platforms such as mRNA and engineered viral vectors.
Keywords: Adenoviral, antibody response, Clinical Trial, HIV-1, Poxviral
Received: 07 Oct 2025; Accepted: 17 Dec 2025.
Copyright: © 2025 M. Manafi, Farzani, Espinoza, Ozonoff and Sabeti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Pardis C Sabeti
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