Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.
To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation ads...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008764 |
| _version_ | 1818348677053284352 |
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| author | Kier Om Dominic Paquin-Proulx Maria Montero Kristina Peachman Xiaoying Shen Lindsay Wieczorek Zoltan Beck Joshua A Weiner Dohoon Kim Yifan Li Thembi Mdluli Zhanna Shubin Christopher Bryant Vishakha Sharma Andrey Tokarev Peter Dawson Yohann White Oliver Appelbe Nichole R Klatt Sodsai Tovanabutra Jacob D Estes Gary R Matyas Guido Ferrari Carl R Alving Georgia D Tomaras Margaret E Ackerman Nelson L Michael Merlin L Robb Victoria Polonis Morgane Rolland Michael A Eller Mangala Rao Diane L Bolton |
| author_facet | Kier Om Dominic Paquin-Proulx Maria Montero Kristina Peachman Xiaoying Shen Lindsay Wieczorek Zoltan Beck Joshua A Weiner Dohoon Kim Yifan Li Thembi Mdluli Zhanna Shubin Christopher Bryant Vishakha Sharma Andrey Tokarev Peter Dawson Yohann White Oliver Appelbe Nichole R Klatt Sodsai Tovanabutra Jacob D Estes Gary R Matyas Guido Ferrari Carl R Alving Georgia D Tomaras Margaret E Ackerman Nelson L Michael Merlin L Robb Victoria Polonis Morgane Rolland Michael A Eller Mangala Rao Diane L Bolton |
| author_sort | Kier Om |
| collection | DOAJ |
| description | To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants. |
| first_indexed | 2024-12-13T17:53:51Z |
| format | Article |
| id | doaj.art-7a6c977bbc934d51bd9ae6ad3d6245bd |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T17:53:51Z |
| publishDate | 2020-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-7a6c977bbc934d51bd9ae6ad3d6245bd2022-12-21T23:36:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-09-01169e100876410.1371/journal.ppat.1008764Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.Kier OmDominic Paquin-ProulxMaria MonteroKristina PeachmanXiaoying ShenLindsay WieczorekZoltan BeckJoshua A WeinerDohoon KimYifan LiThembi MdluliZhanna ShubinChristopher BryantVishakha SharmaAndrey TokarevPeter DawsonYohann WhiteOliver AppelbeNichole R KlattSodsai TovanabutraJacob D EstesGary R MatyasGuido FerrariCarl R AlvingGeorgia D TomarasMargaret E AckermanNelson L MichaelMerlin L RobbVictoria PolonisMorgane RollandMichael A EllerMangala RaoDiane L BoltonTo augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.https://doi.org/10.1371/journal.ppat.1008764 |
| spellingShingle | Kier Om Dominic Paquin-Proulx Maria Montero Kristina Peachman Xiaoying Shen Lindsay Wieczorek Zoltan Beck Joshua A Weiner Dohoon Kim Yifan Li Thembi Mdluli Zhanna Shubin Christopher Bryant Vishakha Sharma Andrey Tokarev Peter Dawson Yohann White Oliver Appelbe Nichole R Klatt Sodsai Tovanabutra Jacob D Estes Gary R Matyas Guido Ferrari Carl R Alving Georgia D Tomaras Margaret E Ackerman Nelson L Michael Merlin L Robb Victoria Polonis Morgane Rolland Michael A Eller Mangala Rao Diane L Bolton Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. PLoS Pathogens |
| title | Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. |
| title_full | Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. |
| title_fullStr | Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. |
| title_full_unstemmed | Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. |
| title_short | Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. |
| title_sort | adjuvanted hiv 1 vaccine promotes antibody dependent phagocytic responses and protects against heterologous shiv challenge |
| url | https://doi.org/10.1371/journal.ppat.1008764 |
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