Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines

Amy W. Chung, Musie Ghebremichael, Hannah Robinson, Eric Brown, Ickwon Choi, Sophie Lane, Anne Sophie Dugast, Matthew K. Schoen, Morgane Rolland, Todd J. Suscovich, Alison E. Mahan, Larry Liao, Hendrik Streeck, Charla Andrews, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Mark S. De Souza, Jaranit Kaewkungwal, Punnee Pitisuttithum, Donald FrancisNelson L. Michael, Jerome H. Kim, Chris Bailey-Kellogg, Margaret E. Ackerman, Galit Alter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

300 Scopus citations


The human phase 2B RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial, held in Thailand, resulted in an estimated 31.2% efficacy against HIV infection. By contrast, vaccination with VAX003 (consisting of only AIDSVAX B/E) was not protective. Because protection within RV144 was observed in the absence of neutralizing antibody activity or cytotoxic T cell responses, we speculated that the specificity or qualitative differences in Fc-effector profiles of nonneutralizing antibodies may have accounted for the efficacy differences observed between the two trials. We show that the RV144 regimen elicited nonneutralizing antibodies with highly coordinated Fc-mediated effector responses through the selective induction of highly functional immunoglobulin G3 (IgG3). By contrast, VAX003 elicited monofunctional antibody responses influenced by IgG4 selection, which was promoted by repeated AIDSVAX B/E protein boosts. Moreover, only RV144 induced IgG1 and IgG3 antibodies targeting the crown of the HIV envelope V2 loop, albeit with limited coverage of breakthrough viral sequences. These data suggest that subclass selection differences associated with coordinated humoral functional responses targeting strain-specific protective V2 loop epitopes may underlie differences in vaccine efficacy observed between these two vaccine trials.

Original languageEnglish
Article number228ra38
JournalScience Translational Medicine
Issue number228
StatePublished - 19 Mar 2014
Externally publishedYes


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