Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial. (21st February 2017)

• Record Type: Journal Article
• Authors: Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Excler, Jean-Louis; Nitayaphan, Sorachai; Kaewkungwal, Jaranit; Premsri, Nakorn; Kunasol, Prayura; Karasavvas, Nicos; Schuetz, Alexandra; Ngauy, Viseth; Sinangil, Faruk; Dawson, Peter; deCamp, Allan C.; Phogat, Sanjay; Garunathan, Sanjay; Tartaglia, James; DiazGranados, Carlos; Ratto-Kim, Silvia; Pegu, Poonam; Eller, Michael; Karnasuta, Chitraporn; Montefiori, David C.; Sawant, Sheetal; Vandergrift, Nathan; Wills, Saintedym; Tomaras, Georgia D.; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Vasan, Sandhya; O'Connell, Robert J.;
• Is Part Of: Journal of infectious diseases. Volume 215:Number 8(2017:Apr. 15)
• Page Start: 1255
• Page End: 1263
• Publication Date: 2017-02-21
• Subjects: HIV -- vaccine -- RV144 -- prime-boost.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix099
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: The RV144 ALVAC-HIV prime, AIDSVAX B/E boost afforded 60% efficacy against human immunodeficiency virus (HIV) acquisition at 1 year, waning to 31.2% after 3.5 years. We hypothesized that additional vaccinations might augment immune correlates of protection. Methods: In a randomized placebo-controlled double-blind study of 162 HIV-negative RV144 vaccine recipients, we evaluated 2 additional boosts, given 6–8 years since RV144 vaccination, for safety and immunogenicity, at weeks 0 and 24. Study groups 1–3 received ALVAC-HIV+AIDSVAX B/E, AIDSVAX B/E, and ALVAC-HIV, respectively, or placebo. Results: Vaccines were well tolerated. For groups 1 and 2, plasma immunoglobulin (Ig) G, IgA, and neutralizing antibody responses at week 2 were all significantly higher than 2 weeks after the last RV144 vaccination. IgG titers against glycoprotein (gp) 70V1V2 92TH023 increased 14-fold compared with 2 weeks after the last RV144 vaccination (14069 vs 999; P < .001). Groups 1 and 2 did not differ significantly from each other, whereas group 3 was similar to placebo recipients. Responses in groups 1 and 2 declined by week 24 but were boosted by the second vaccination, albeit at lower magnitude than for week 2. Conclusions: In RV144 vaccinees, AIDSVAX B/E with or without ALVAC-HIV 6–8 years after initial vaccination generated higher humoral responses than after RV144, but these responses were short-lived, and their magnitude did not increase with subsequent boost. Clinical Trials Registration: NCT01435135.