Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response
Abstract Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increas...
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2024-10-01
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| Online Access: | https://doi.org/10.1038/s41467-024-53359-2 |
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| author | Mohammad Arif Rahman Massimiliano Bissa Hanna Scinto Savannah E. Howe Sarkis Sarkis Zhong-Min Ma Anna Gutowska Xunqing Jiang Christina C. Luo Luca Schifanella Ramona Moles Isabela Silva de Castro Shraddha Basu Kombo F. N’guessan LaTonya D. Williams Manuel Becerra-Flores Melvin N. Doster Tanya Hoang Hyoyoung Choo-Wosoba Emmanuel Woode Yongjun Sui Georgia D. Tomaras Dominic Paquin-Proulx Mangala Rao James D. Talton Xiang-Peng Kong Susan Zolla-Pazner Timothy Cardozo Genoveffa Franchini Jay A. Berzofsky |
| author_facet | Mohammad Arif Rahman Massimiliano Bissa Hanna Scinto Savannah E. Howe Sarkis Sarkis Zhong-Min Ma Anna Gutowska Xunqing Jiang Christina C. Luo Luca Schifanella Ramona Moles Isabela Silva de Castro Shraddha Basu Kombo F. N’guessan LaTonya D. Williams Manuel Becerra-Flores Melvin N. Doster Tanya Hoang Hyoyoung Choo-Wosoba Emmanuel Woode Yongjun Sui Georgia D. Tomaras Dominic Paquin-Proulx Mangala Rao James D. Talton Xiang-Peng Kong Susan Zolla-Pazner Timothy Cardozo Genoveffa Franchini Jay A. Berzofsky |
| author_sort | Mohammad Arif Rahman |
| collection | DOAJ |
| description | Abstract Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission. |
| format | Article |
| id | doaj-art-c46022c8eff943a69e28ba2d4818429f |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
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| spelling | doaj-art-c46022c8eff943a69e28ba2d4818429f2025-08-20T02:11:29ZengNature PortfolioNature Communications2041-17232024-10-0115111910.1038/s41467-024-53359-2Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific responseMohammad Arif Rahman0Massimiliano Bissa1Hanna Scinto2Savannah E. Howe3Sarkis Sarkis4Zhong-Min Ma5Anna Gutowska6Xunqing Jiang7Christina C. Luo8Luca Schifanella9Ramona Moles10Isabela Silva de Castro11Shraddha Basu12Kombo F. N’guessan13LaTonya D. Williams14Manuel Becerra-Flores15Melvin N. Doster16Tanya Hoang17Hyoyoung Choo-Wosoba18Emmanuel Woode19Yongjun Sui20Georgia D. Tomaras21Dominic Paquin-Proulx22Mangala Rao23James D. Talton24Xiang-Peng Kong25Susan Zolla-Pazner26Timothy Cardozo27Genoveffa Franchini28Jay A. Berzofsky29Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthVaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthVaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthCalifornia National Primate Research Center, University of CaliforniaAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of MedicineDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of MedicineAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthUnited States Military HIV Research Program, CIDR, Walter Reed Army Institute of ResearchUnited States Military HIV Research Program, CIDR, Walter Reed Army Institute of ResearchCenter for Human Systems Immunology, Department of Surgery, Duke University School of MedicineNew York University School of Medicine, NYU Langone HealthAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthVaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthOffice of Collaborative Biostatistics, Center for Cancer Research, National Cancer InstituteAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthVaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthCenter for Human Systems Immunology, Department of Surgery, Duke University School of MedicineUnited States Military HIV Research Program, CIDR, Walter Reed Army Institute of ResearchUnited States Military HIV Research Program, CIDR, Walter Reed Army Institute of ResearchAlchem Laboratories CorporationDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of MedicineDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount SinaiNew York University School of Medicine, NYU Langone HealthAnimal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthVaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAbstract Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.https://doi.org/10.1038/s41467-024-53359-2 |
| spellingShingle | Mohammad Arif Rahman Massimiliano Bissa Hanna Scinto Savannah E. Howe Sarkis Sarkis Zhong-Min Ma Anna Gutowska Xunqing Jiang Christina C. Luo Luca Schifanella Ramona Moles Isabela Silva de Castro Shraddha Basu Kombo F. N’guessan LaTonya D. Williams Manuel Becerra-Flores Melvin N. Doster Tanya Hoang Hyoyoung Choo-Wosoba Emmanuel Woode Yongjun Sui Georgia D. Tomaras Dominic Paquin-Proulx Mangala Rao James D. Talton Xiang-Peng Kong Susan Zolla-Pazner Timothy Cardozo Genoveffa Franchini Jay A. Berzofsky Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response Nature Communications |
| title | Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response |
| title_full | Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response |
| title_fullStr | Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response |
| title_full_unstemmed | Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response |
| title_short | Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response |
| title_sort | loss of hiv candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by v2 specific response |
| url | https://doi.org/10.1038/s41467-024-53359-2 |
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