TY - JOUR
T1 - Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response
AU - RV305 Study Team
AU - Williams, La Tonya D.
AU - Shen, Xiaoying
AU - Sawant, Sheetal S.
AU - Akapirat, Siriwat
AU - Dahora, Lindsay C.
AU - Tay, Matthew Zirui
AU - Stanfield-Oakley, Sherry
AU - Wills, Saintedym
AU - Goodman, Derrick
AU - Tenney, De Anna
AU - Spreng, Rachel L.
AU - Zhang, Lu
AU - Yates, Nicole L.
AU - Montefiori, David C.
AU - Eller, Michael A.
AU - Easterhoff, David
AU - Hope, Thomas J.
AU - Rerks-Ngarm, Supachai
AU - Pittisuttithum, Punnee
AU - Nitayaphan, Sorachai
AU - Excler, Jean Louis
AU - Kim, Jerome H.
AU - Michael, Nelson L.
AU - Robb, Merlin L.
AU - O’Connell, Robert J.
AU - Karasavvas, Nicos
AU - Vasan, Sandhya
AU - Ferrari, Guido
AU - Tomaras, Georgia D.
N1 - Publisher Copyright:
© 2023 Public Library of Science. All rights reserved.
PY - 2023/5
Y1 - 2023/5
N2 - The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6–8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population.
AB - The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6–8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population.
UR - http://www.scopus.com/inward/record.url?scp=85163920490&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1011359
DO - 10.1371/journal.ppat.1011359
M3 - Article
C2 - 37256916
AN - SCOPUS:85163920490
SN - 1553-7366
VL - 19
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 5 MAY
M1 - e1011359
ER -