PT  - JOURNAL ARTICLE
AU  - Chung, Amy W.
AU  - Ghebremichael, Musie
AU  - Robinson, Hannah
AU  - Brown, Eric
AU  - Choi, Ickwon
AU  - Lane, Sophie
AU  - Dugast, Anne-Sophie
AU  - Schoen, Matthew K.
AU  - Rolland, Morgane
AU  - Suscovich, Todd J.
AU  - Mahan, Alison E.
AU  - Liao, Larry
AU  - Streeck, Hendrik
AU  - Andrews, Charla
AU  - Rerks-Ngarm, Supachai
AU  - Nitayaphan, Sorachai
AU  - de Souza, Mark S.
AU  - Kaewkungwal, Jaranit
AU  - Pitisuttithum, Punnee
AU  - Francis, Donald
AU  - Michael, Nelson L.
AU  - Kim, Jerome H.
AU  - Bailey-Kellogg, Chris
AU  - Ackerman, Margaret E.
AU  - Alter, Galit
TI  - Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines
AID  - 10.1126/scitranslmed.3007736
DP  - 2014 Mar 19
TA  - Science Translational Medicine
PG  - 228ra38--228ra38
VI  - 6
IP  - 228
4099  - http://stm.sciencemag.org/content/6/228/228ra38.short
4100  - http://stm.sciencemag.org/content/6/228/228ra38.full
AB  - 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.