Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.
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 immunit...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011359 |
| _version_ | 1827321130970513408 |
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| author | LaTonya D Williams Xiaoying Shen Sheetal S Sawant Siriwat Akapirat Lindsay C Dahora Matthew Zirui Tay Sherry Stanfield-Oakley Saintedym Wills Derrick Goodman DeAnna Tenney Rachel L Spreng Lu Zhang Nicole L Yates David C Montefiori Michael A Eller David Easterhoff Thomas J Hope Supachai Rerks-Ngarm Punnee Pittisuttithum Sorachai Nitayaphan Jean-Louis Excler Jerome H Kim Nelson L Michael Merlin L Robb Robert J O'Connell Nicos Karasavvas Sandhya Vasan Guido Ferrari Georgia D Tomaras RV305 study team |
| author_facet | LaTonya D Williams Xiaoying Shen Sheetal S Sawant Siriwat Akapirat Lindsay C Dahora Matthew Zirui Tay Sherry Stanfield-Oakley Saintedym Wills Derrick Goodman DeAnna Tenney Rachel L Spreng Lu Zhang Nicole L Yates David C Montefiori Michael A Eller David Easterhoff Thomas J Hope Supachai Rerks-Ngarm Punnee Pittisuttithum Sorachai Nitayaphan Jean-Louis Excler Jerome H Kim Nelson L Michael Merlin L Robb Robert J O'Connell Nicos Karasavvas Sandhya Vasan Guido Ferrari Georgia D Tomaras RV305 study team |
| author_sort | LaTonya D Williams |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T01:34:21Z |
| format | Article |
| id | doaj.art-e0502dca070d4a5f86962367ed6a51ba |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-25T00:59:56Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-e0502dca070d4a5f86962367ed6a51ba2024-03-11T05:31:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-05-01195e101135910.1371/journal.ppat.1011359Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.LaTonya D WilliamsXiaoying ShenSheetal S SawantSiriwat AkapiratLindsay C DahoraMatthew Zirui TaySherry Stanfield-OakleySaintedym WillsDerrick GoodmanDeAnna TenneyRachel L SprengLu ZhangNicole L YatesDavid C MontefioriMichael A EllerDavid EasterhoffThomas J HopeSupachai Rerks-NgarmPunnee PittisuttithumSorachai NitayaphanJean-Louis ExclerJerome H KimNelson L MichaelMerlin L RobbRobert J O'ConnellNicos KarasavvasSandhya VasanGuido FerrariGeorgia D TomarasRV305 study teamThe 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.https://doi.org/10.1371/journal.ppat.1011359 |
| spellingShingle | LaTonya D Williams Xiaoying Shen Sheetal S Sawant Siriwat Akapirat Lindsay C Dahora Matthew Zirui Tay Sherry Stanfield-Oakley Saintedym Wills Derrick Goodman DeAnna Tenney Rachel L Spreng Lu Zhang Nicole L Yates David C Montefiori Michael A Eller David Easterhoff Thomas J Hope Supachai Rerks-Ngarm Punnee Pittisuttithum Sorachai Nitayaphan Jean-Louis Excler Jerome H Kim Nelson L Michael Merlin L Robb Robert J O'Connell Nicos Karasavvas Sandhya Vasan Guido Ferrari Georgia D Tomaras RV305 study team Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. PLoS Pathogens |
| title | Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. |
| title_full | Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. |
| title_fullStr | Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. |
| title_full_unstemmed | Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. |
| title_short | Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response. |
| title_sort | viral vector delivered immunogen focuses hiv 1 antibody specificity and increases durability of the circulating antibody recall response |
| url | https://doi.org/10.1371/journal.ppat.1011359 |
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