Late Boosting of the RV144 Regimen Improves the Magnitude and Quality of Immune Responses

Abstract

Background: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX® B/E administration over six months resulted in a 31% efficacy in preventing HIV acquisition. Subsequent boosting of RV144 vaccine recipients 6 to 8 years later improved the magnitude and quality of immune responses, expanding subdominant memory B cells. Methods: RV306 is a double-blind, placebo-controlled, randomized clinical trial of the primary RV144 vaccine series with additional AIDSVAX® B/E with or without ALVAC-HIV boosting at months 12, 15, or 18 in healthy volunteers. Findings: Late boosting was safe, and improved antigen-specific plasma IgG responses to HIV-1 envelope and the first and second variable loops (V1V2), an inverse correlate of HIV risk in RV144, without increasing HIV-specific plasma IgA, a direct correlate of risk. Late boosting improved Tier 1 neutralization and HIV-1 envelope-specific CD4+ T cell polyfunctionality, an independent correlate contributing to RV144 vaccine efficacy. Late boosting was also required to maintain antigen-specific CD4+ T cell proliferation. Interestingly, increasing the interval between priming and boosting improved several humoral and cellular immune responses. Interpretation: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and may improve the efficacy of preventing HIV acquisition. Funding Statement: Cooperative Agreement # W81XWH-18-2-0040 in collaboration with the US Army and DAIDS/NIAID/NIH. Declaration of Interests: J. T., and C. D. are employees of Sanofi Pasteur. S.P. was an employee of Sanofi Pasteur during the conduct of this study and analysis. F. S. is an employee of Global Solutions for Infectious Diseases. All other authors report no potential conflicts. The opinions expressed herein are those of the authors and do not represent the official position of the US Army or the Department of Defense. Trade names are used for identification purposes only and do not imply endorsement. Ethics Approval Statement: The study was approved by ethical review boards at the Walter Reed Army Institute of Research, Thai Ministry of Public Health, Royal Thai Army Medical Department, Faculty of Tropical Medicine, Mahidol University, Chiang Mai University, and Chulalongkorn University Faculty of Medicine. This study was conducted in accordance with Good Participatory Practice principles.