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Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response

Williams, LaTonya D ; Shen, Xiaoying ; Sawant, Sheetal S ; Akapirat, Siriwat ; Dahora, Lindsay C ; Tay, Matthew Zirui ; Stanfield-Oakley, Sherry ; Wills, Saintedym ; Goodman, Derrick ; Tenney, DeAnna ; Spreng, Rachel L ; Zhang, Lu ; Yates, Nicole L ; Montefiori, David C ; Eller, Michael A ; Easterhoff, David ; Hope, Thomas J ; Rerks-Ngarm, Supachai ; Pittisuttithum, Punnee ; Nitayaphan, Sorachai ; Excler, Jean-Louis ; Kim, Jerome H ; Michael, Nelson L ; Robb, Merlin L ; O'Connell, Robert J ; Karasavvas, Nicos ; Vasan, Sandhya ; Ferrari, Guido ; Tomaras, Georgia D Douek, Daniel C.

PLoS pathogens, 2023-05, Vol.19 (5), p.e1011359-e1011359 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response
Autor: Williams, LaTonya D ; Shen, Xiaoying ; Sawant, Sheetal S ; Akapirat, Siriwat ; Dahora, Lindsay C ; Tay, Matthew Zirui ; Stanfield-Oakley, Sherry ; Wills, Saintedym ; Goodman, Derrick ; Tenney, DeAnna ; Spreng, Rachel L ; Zhang, Lu ; Yates, Nicole L ; Montefiori, David C ; Eller, Michael A ; Easterhoff, David ; Hope, Thomas J ; Rerks-Ngarm, Supachai ; Pittisuttithum, Punnee ; Nitayaphan, Sorachai ; Excler, Jean-Louis ; Kim, Jerome H ; Michael, Nelson L ; Robb, Merlin L ; O'Connell, Robert J ; Karasavvas, Nicos ; Vasan, Sandhya ; Ferrari, Guido ; Tomaras, Georgia D
Douek, Daniel C.
Assuntos: Acquired immune deficiency syndrome ; AIDS ; AIDS Vaccines ; Analysis ; Antibodies ; Antibody Formation ; Antibody response ; Antibody Specificity ; Antigenic determinants ; Antigens ; Biology and life sciences ; Correlation ; Cytotoxicity ; Dosage and administration ; Durability ; Epitopes ; Genetic vectors ; Glycoprotein gp120 ; Health aspects ; Health risks ; HIV ; HIV (Viruses) ; HIV Antibodies ; HIV Envelope Protein gp120 ; HIV infection ; HIV Infections - prevention & control ; HIV Seropositivity ; HIV-1 ; Human immunodeficiency virus ; Humans ; Immune response ; Immunity ; Immunization ; Immunization, Secondary - methods ; Immunoglobulin A ; Immunoglobulin G ; Immunology ; Infection ; Infections ; Medicine and health sciences ; Patient outcomes ; Phagocytosis ; Plasma ; Prevention ; Proteins ; Research and Analysis Methods ; Response rates ; Risk ; Toxicity ; Vaccination ; Vaccine efficacy ; Vaccines ; Viruses
É parte de: PLoS pathogens, 2023-05, Vol.19 (5), p.e1011359-e1011359
Notas: new_version
ObjectType-Article-1
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Current address: International Vaccine Institute, Seoul, Republic of Korea
Current address: Diagnostics and Countermeasures Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America
These authors are joint senior authors on this work.
The authors have declared that no competing interests exist.
Current address: Vaccine Translational Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America
RV305 study team members are listed in the Acknowledgements
Current address: Moderna Therapeutics, Cambridge, Massachusetts, United States of America
Current address: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America
Descrição: 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. Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080.
Editor: United States: Public Library of Science
Idioma: Inglês

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Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response

United States: Public Library of Science

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