TY - JOUR
T1 - ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone
AU - RV306
AU - RV328 study groups
AU - Costanzo, Margaret C.
AU - Paquin-Proulx, Dominic
AU - Schuetz, Alexandra
AU - Akapirat, Siriwat
AU - Shubin, Zhanna
AU - Kim, Dohoon
AU - Wieczorek, Lindsay
AU - Polonis, Victoria R.
AU - Trinh, Hung V.
AU - Rao, Mangala
AU - Anenia, Hanna
AU - Barrera, Michael D.
AU - Boeckelman, Jacob
AU - Nails, Barbara
AU - Thapa, Pallavi
AU - Zemil, Michelle
AU - Sacdalan, Carlo
AU - Kroon, Eugene
AU - Kaewboon, Boot
AU - Tipsuk, Somporn
AU - Jongrakthaitae, Surat
AU - Gurunathan, Sanjay
AU - Sinangil, Faruk
AU - Kim, Jerome H.
AU - Robb, Merlin L.
AU - Ake, Julie A.
AU - O’Connell, Robert J.
AU - Pitisutthithum, Punnee
AU - Nitayaphan, Sorachai
AU - Chariyalertsak, Suwat
AU - Eller, Michael A.
AU - Phanuphak, Nittaya
AU - Vasan, Sandhya
N1 - Funding Information:
We are deeply grateful to the RV306 and RV328 participants for their participation and dedication to this study, as well as our Community Advisory Boards for their helpful input. See Supplemental Acknowledgments for RV306 and RV328 details. This work was supported by the US Army Medical Research and Materiel Command (Military Infectious Diseases Research Program; cooperative agreement W81XWH-18-2-0040 with the Henry M. Jackson Foundation for the Advancement of Military Medicine), the US Army Medical Materiel Development Activity, and the National Institute of Allergy and Infectious Diseases (interagency agreement Y1-AI-2642-12 with the US Army Medical Research and Materiel Command). The views expressed are those of the authors and should not be construed to represent the positions of the US Army, the Department of Defense, nor the Henry M. Jackson Foundation for the Advancement of Military Medicine. The investigators have adhered to the policies for protection of human participants as prescribed in AR 70-25. Trade names are used for identification purposes only and do not imply endorsement.
Publisher Copyright:
© 2023, Costanzo et.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85158076140&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.167664
DO - 10.1172/jci.insight.167664
M3 - Article
C2 - 37154156
AN - SCOPUS:85158076140
SN - 2379-3708
VL - 8
JO - JCI Insight
JF - JCI Insight
IS - 9
M1 - e167664
ER -