ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone
Margaret C. Costanzo, Dominic Paquin-Proulx, Alexandra Schuetz, Siriwat Akapirat, Zhanna Shubin, Dohoon Kim, Lindsay Wieczorek, Victoria R. Polonis, Hung V. Trinh, Mangala Rao, Hanna Anenia, Michael D. Barrera, Jacob Boeckelman, Barbara Nails, Pallavi Thapa, Michelle Zemil, Carlo Sacdalan, Eugene Kroon, Boot Kaewboon, Somporn Tipsuk, Surat Jongrakthaitae, Sanjay Gurunathan, Faruk Sinangil, Jerome H. Kim, Merlin L. Robb, Julie A. Ake, Robert J. O’Connell, Punnee Pitisutthithum, Sorachai Nitayaphan, Suwat Chariyalertsak, Michael A. Eller, Nittaya Phanuphak, Sandhya Vasan, the RV306, RV328 study groups
Margaret C. Costanzo, Dominic Paquin-Proulx, Alexandra Schuetz, Siriwat Akapirat, Zhanna Shubin, Dohoon Kim, Lindsay Wieczorek, Victoria R. Polonis, Hung V. Trinh, Mangala Rao, Hanna Anenia, Michael D. Barrera, Jacob Boeckelman, Barbara Nails, Pallavi Thapa, Michelle Zemil, Carlo Sacdalan, Eugene Kroon, Boot Kaewboon, Somporn Tipsuk, Surat Jongrakthaitae, Sanjay Gurunathan, Faruk Sinangil, Jerome H. Kim, Merlin L. Robb, Julie A. Ake, Robert J. O’Connell, Punnee Pitisutthithum, Sorachai Nitayaphan, Suwat Chariyalertsak, Michael A. Eller, Nittaya Phanuphak, Sandhya Vasan, the RV306, RV328 study groups
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Research Article AIDS/HIV

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

Abstract

The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.

Authors

Margaret C. Costanzo, Dominic Paquin-Proulx, Alexandra Schuetz, Siriwat Akapirat, Zhanna Shubin, Dohoon Kim, Lindsay Wieczorek, Victoria R. Polonis, Hung V. Trinh, Mangala Rao, Hanna Anenia, Michael D. Barrera, Jacob Boeckelman, Barbara Nails, Pallavi Thapa, Michelle Zemil, Carlo Sacdalan, Eugene Kroon, Boot Kaewboon, Somporn Tipsuk, Surat Jongrakthaitae, Sanjay Gurunathan, Faruk Sinangil, Jerome H. Kim, Merlin L. Robb, Julie A. Ake, Robert J. O’Connell, Punnee Pitisutthithum, Sorachai Nitayaphan, Suwat Chariyalertsak, Michael A. Eller, Nittaya Phanuphak, Sandhya Vasan, the RV306, RV328 study groups

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Figure 3

Plasma IgG HIV-1 Env and V1V2 antibody binding titers and avidity of antibody-antigen interaction are significantly higher with ALVAC-HIV.

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Plasma IgG HIV-1 Env and V1V2 antibody binding titers and avidity of ant...
(A and B) IgG antibody binding titers for HIV-1 gp120 and scaffolded gp70 V1V2 antigens were measured by ELISA. Each symbol represents the average of triplicate measurements for a participant. Geometric mean antibody titers against gp120 A244gD– D11 (A, left), gp120 MNgD– D11 (A, right), gp70 V1V2 (92TH023) (B, left), and gp70 V1V2 (case A2) (B, right) are shown. Each panel graphically displays geometric mean titers, color-coded by group. Error bars depict 95% CIs. Statistical significance was assessed using the Mann-Whitney U test with step-down Bonferroni adjustment. n = 190 for participants receiving ALVAC-HIV and AIDSVAX B/E and n = 30 for those who received AIDSVAX B/E alone. (C) Kd off-rate (1/s). A lower Kd off-rate corresponds to higher avidity. Statistical analysis was performed using the rank-based nonparametric 1-way ANOVA (Kruskal-Wallis H test). The FDR was determined using the 2-stage step-up method of Benjamini, Krieger, and Yekutieli, with confidence level at 0.05. For Kd off-rate with A244, n = 62 for participants receiving ALVAC-HIV and AIDSVAX B/E and n = 23 for those who received AIDSVAX B/E alone. For Kd off-rate with MN, n = 58 for participants receiving ALVAC-HIV and AIDSVAX B/E and n = 25 for those who received AIDSVAX B/E alone. Data are shown as the mean and 95% CI.