Varatharajan S, Krishnasai S, Girish C. Human immunodeficiency virus vaccines: Advances, challenges and future perspectives. World J Virol 2026; 15(1): 116055 [DOI: 10.5501/wjv.v15.i1.116055]
Corresponding Author of This Article
Chandrashekaran Girish, PhD, Additional Professor, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Puducherry 605006, India. gcnx2005@gmail.com
Research Domain of This Article
Virology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Subashchandrabose Varatharajan, Sathiamoorthy Krishnasai, Chandrashekaran Girish, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Co-corresponding authors: Sathiamoorthy Krishnasai and Chandrashekaran Girish.
Author contributions: Varatharajan S and Krishnasai S was responsible for data collection, writing the original draft; Girish C was responsible for supervision; Girish C and Krishnasai S were responsible for conceptualization and review and editing, have played important and indispensable roles in the manuscript preparation as the co-corresponding authors.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Chandrashekaran Girish, PhD, Additional Professor, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Puducherry 605006, India. gcnx2005@gmail.com
Received: November 2, 2025 Revised: January 1, 2026 Accepted: February 11, 2026 Published online: March 25, 2026 Processing time: 132 Days and 3.2 Hours
Abstract
In the past 40 years, much effort has been made to develop a vaccine that can prevent human immunodeficiency virus (HIV) infection. But till today, this continues to be an unresolved challenge. The main obstacle in developing a vaccine is the ability of the virus to mutate at a swift rate, thereby evading the immune system. This has dramatically slowed the progress in the development of an HIV vaccine. Previous studies, like RV144, have demonstrated limited protection. Current trials, such as Imbokodo and Mosaico, have shown that the vaccines used were safe but did not demonstrate efficacy against the HIV-1 virus. With the advent of mRNA vaccines and broad neutralising antibodies, research has shown some progress in developing a promising candidate vaccine. Recently, the use of mosaic antigens and germline-targeting techniques has shed light on the development of a promising candidate vaccine. These techniques educate the immune system slowly. This review tracks the progress of HIV vaccine development to date and examines the most promising new strategies that could ultimately lead to the development of an efficacious vaccine.
Core Tip: The article primarily focuses on the hurdles in developing a successful vaccine for human immunodeficiency virus-1, lessons learnt from some of the landmark trials, and the targets to be induced by a successful vaccine, and briefly touches on some current advances.
