FIG 8.
Poor cross-reactivity of vaccine-induced antibody to the challenge virus V1V2 and V2 HS. (A) 1157 gp120 IgG responses in the blood at the peak and prechallenge time points in DDMMM- and DDMMPP-immunized RMs. (B) 1157 gp70 V1V2 IgG responses in the blood at the peak and prechallenge time points in DDMMM- and DDMMPP-immunized RMs. Correlations between responses against 1157 V1V2 and C.1086 V1V2 are shown on the right. (C) V2 HS sequences for the clade C consensus sequence, 1086c, and 1157ipd3N4. (D) ELISA data showing binding of individual RM sera to the 1086c peptide (TELKDKKHKVHALFY) and 1157 V2 HS peptide (TELRDKKQKVYALFY) for each immunization group. O.D., optical density. (E) Pooled peak serum from DDMMPP-immunized RMs against C.1086 V2 HS singly or doubly mutated peptides. (F) ELISA data showing binding of mAb CH59 to the 1086c and 1157 V2 HS sequences. (G) Flow cytometry data demonstrating binding of CH59 to CEM NKr cells infected with SHIV1157ipd3N4 and SHIV1157(QNE)Y173H. (H) ADCC activity of CH59 against SHIV1157ipd3N4- and SHIV1157(QNE)Y173H-infected CEM NKr cells. (I) Representative flow data demonstrating binding of PGT121 and CH59 mAbs and serum from DDMMPP animals to DNA-transfected cells. C.1086 is the vaccine DNA without CD40L. C.1086 (RQ)H173Y DNA is identical to C.1086 except for three mutations in the HS, K166R, H170Q, and H173Y. wt, wild type. (J) Binding of DDMMPP sera to DNA-transfected cells. (K) Binding to DNA/SHIV-C.1086-CD40L (KHH and RQY)-transfected (left) and SHIV1157ipd3N4/SHIV1157(QNE)Y173H-infected (right) cells using mAbs PGT121 and CH59. (L) ADCC activity against SHIV1157ipd3N4 and SHIV1157(QNE)Y173H. DNA1, time point used as the background for the assay. **, P < 0.01; ****, P < 0.0001.