RT Journal Article
SR Electronic
T1 Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 228ra38
OP 228ra38
DO 10.1126/scitranslmed.3007736
VO 6
IS 228
A1 Chung, Amy W.
A1 Ghebremichael, Musie
A1 Robinson, Hannah
A1 Brown, Eric
A1 Choi, Ickwon
A1 Lane, Sophie
A1 Dugast, Anne-Sophie
A1 Schoen, Matthew K.
A1 Rolland, Morgane
A1 Suscovich, Todd J.
A1 Mahan, Alison E.
A1 Liao, Larry
A1 Streeck, Hendrik
A1 Andrews, Charla
A1 Rerks-Ngarm, Supachai
A1 Nitayaphan, Sorachai
A1 de Souza, Mark S.
A1 Kaewkungwal, Jaranit
A1 Pitisuttithum, Punnee
A1 Francis, Donald
A1 Michael, Nelson L.
A1 Kim, Jerome H.
A1 Bailey-Kellogg, Chris
A1 Ackerman, Margaret E.
A1 Alter, Galit
YR 2014
UL http://stm.sciencemag.org/content/6/228/228ra38.abstract
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.