TY - JOUR
T1 - V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144
AU - Perez, Lautaro G.
AU - Martinez, David R.
AU - DeCamp, Allan C.
AU - Pinter, Abraham
AU - Berman, Phillip W.
AU - Francis, Donald
AU - Sinangil, Faruk
AU - Lee, Carter
AU - Greene, Kelli
AU - Gao, Hongmei
AU - Nitayaphan, Sorachai
AU - Rerks-Ngarm, Supachai
AU - Kaewkungwal, Jaranit
AU - Pitisuttithum, Punnee
AU - Tartaglia, James
AU - O'Connell, Robert J.
AU - Robb, Merlin L.
AU - Michael, Nelson L.
AU - Kim, Jerome H.
AU - Gilbert, Peter
AU - Montefiori, David C.
PY - 2017/7
Y1 - 2017/7
N2 - Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01-AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.
AB - Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01-AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.
UR - http://www.scopus.com/inward/record.url?scp=85022035434&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0180720
DO - 10.1371/journal.pone.0180720
M3 - Article
C2 - 28678869
AN - SCOPUS:85022035434
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e0180720
ER -