Biologicals 23:159C164. studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and decided the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV contamination model. 0.05). Open in a separate window FIG 2 CON-S vaccination induces higher plasma antibody blocking of the V3-glycan and CD4 binding site on HIV-1 Env. Plasma competition ELISAs for various broadly neutralizing and nonneutralizing monoclonal antibodies that bind to various sites on HIV-1 Env were performed. The antibody and Env used for competition are indicated above each graph. Values are the means and SDs for all those six animals. Values for each macaque were measured in triplicate. Twenty percent is the cutoff for positive blocking responses. *, exact Wilcoxon test, FDR corrected, 0.05. Vaccination elicits heterologous tier 1 neutralizing antibodies and autologous tier 2 neutralizing antibodies. The neutralizing antibody responses were compared for each group at the end of the vaccination regimen using the TZM-bl cell assay. All three groups possessed heterologous tier 1, but not heterologous tier 2, neutralizing antibodies (Fig. 3A and ?andB).B). CON-S vaccination elicited the highest neutralizing titers against the tier 1 viruses (Fig. 3B). Open in a separate window FIG 3 Protein boosts maintain heterologous tier 1 plasma neutralizing antibodies but not autologous tier 2 plasma neutralizing antibodies. (A) Week 84 (2 NYVAC/5 gp120) plasma neutralization activity against a panel of tier 1 and Irsogladine 2 viruses by each vaccinated macaque in each group. The immunization group is usually indicated in the column header. The neutralization titer is usually shown as reciprocal plasma dilution that yields 50% inhibition of virus replication (ID50). Neutralization titers are color-coded based on neutralization potency as follows: white, 20; yellow, 20 to 99; orange, 100 Irsogladine to 999; and red, 1,000. (B) Comparison of neutralization titers (ID50) elicited by the three immunogens against MN.3 (left) and MW965.26 (right). (C) Comparison of tier 1 neutralization titers (ID50) elicited by NYVAC-protein (orange), DNA-NYVAC (purple), and DNA-NYVAC-protein (brown) vaccination regimens. Immunogens used for the vaccination regimen are listed on the axis. (D and E) Week 30 and 84 plasma neutralization of autologous IL23R antibody tier 1 and 2 viruses (D) and heterologous tier 1 virus MN.3 (E) by each macaque vaccinated with B.1059, CON-S, and T cell mosaic envelopes. Neutralization was tested before vaccination (week 0), after two NYVAC primes and 3 protein boosts (week 30), and after two NYVAC primes and 5 protein boosts (week 84). Each symbol represents the neutralization titer (ID50) of an individual macaque. We compared the neutralizing antibody responses elicited in this study to those elicited in our previous studies in which macaques were immunized with DNA-NYVAC or DNA-NYVAC-protein vaccines. When B.1059 was the immunogen, NYVAC prime-protein boost elicited higher neutralizing antibody titers than the other two vaccine regimens (exact Wilcoxon test corrected = 0.006 [Fig. 3C]). In the absence of heterologous tier 2 neutralization, it is possible to elicit autologous tier 2 neutralizing antibodies (36,C38). Autologous tier 2 neutralizing antibodies did not arise in the B.1059-immunized group, although heterologous tier 1 antibodies were elicited (Fig. 3D and ?andE).E). In contrast, CON-S-immunized macaques possessed autologous tier 2 neutralizing activity in plasma. The neutralizing activity was not boosted with subsequent immunizations, suggesting immunologic restraints on the neutralizing B cell clones. Tier 1 neutralizing antibodies, however, did persist throughout the vaccination regimen (Fig. 3D and ?andE).E). T cell mosaic 3.2 virus (tier 1A virus) was neutralized by the autologous plasma at weeks 30 and 84 but to a lower titer than MN.3 (Fig. 3D and ?andEE). Detection of antibody effector functions, but not neutralizing antibodies against SHIV SF162P3. After the final immunization, all macaques possessed binding antibodies to SF162 gp120 and SF162 gp140 (Fig. 4A). The median titers Irsogladine of binding antibodies to both SF162 gp120 and gp140 were comparable among the three groups, and the differences were not significant. Open in a separate window FIG 4 Vaccination-induced antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis.
Biologicals 23:159C164