Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women
The RV144 HIV-vaccine trial highlighted the importance of envelope-specific non-neutralizing antibody (nNAb) Fc-mediated functions as immune correlates of reduced risk of infection. Since pre-exposure prophylaxis (PrEP) and HIV-vaccines are being used as a combination prevention strategy in at risk...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01274/full |
| _version_ | 1818127601188732928 |
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| author | Kimone Leigh Fisher Jennifer M. Mabuka Jennifer M. Mabuka Aida Sivro Aida Sivro Sinaye Ngcapu Sinaye Ngcapu Jo-Ann Shelley Passmore Jo-Ann Shelley Passmore Farzana Osman Bongiwe Ndlovu Quarraisha Abdool Karim Quarraisha Abdool Karim Salim S. Abdool Karim Salim S. Abdool Karim Amy W. Chung Cheryl Baxter Cheryl Baxter Derseree Archary Derseree Archary |
| author_facet | Kimone Leigh Fisher Jennifer M. Mabuka Jennifer M. Mabuka Aida Sivro Aida Sivro Sinaye Ngcapu Sinaye Ngcapu Jo-Ann Shelley Passmore Jo-Ann Shelley Passmore Farzana Osman Bongiwe Ndlovu Quarraisha Abdool Karim Quarraisha Abdool Karim Salim S. Abdool Karim Salim S. Abdool Karim Amy W. Chung Cheryl Baxter Cheryl Baxter Derseree Archary Derseree Archary |
| author_sort | Kimone Leigh Fisher |
| collection | DOAJ |
| description | The RV144 HIV-vaccine trial highlighted the importance of envelope-specific non-neutralizing antibody (nNAb) Fc-mediated functions as immune correlates of reduced risk of infection. Since pre-exposure prophylaxis (PrEP) and HIV-vaccines are being used as a combination prevention strategy in at risk populations, the effects of PrEP on nNAb functions both mucosally and systemically remain undefined. Previous animal and human studies demonstrated reduced HIV-specific antibody binding avidity post-HIV seroconversion with PrEP, which in turn may affect antibody functionality. In seroconverters from the CAPRISA 004 tenofovir gel trial, we previously reported significantly higher detection and titres of HIV-specific binding antibodies in the plasma and genital tract (GT) that distinguished the tenofovir from the placebo arm. We hypothesized that higher HIV-specific antibody titres and detection reflected corresponding increased antibody-dependent neutrophil-mediated phagocytosis (ADNP) and NK-cell-activated antibody-dependent cellular cytotoxic (ADCC) activities. HIV-specific V1V2-gp70, gp120, gp41, p66, and p24 antibodies in GT and plasma samples of 48 seroconverters from the CAPRISA 004 tenofovir gel trial were tested for ADCP and ADCC at 3, 6- and 12-months post-HIV-infection. GT gp41- and p24-specific ADNP were significantly higher in the tenofovir than the placebo arm at 6 and 12 months respectively (p < 0.05). Plasma gp120-, gp41-, and p66-specific ADNP, and GT gp41-specific ADCC increased significantly over time (p < 0.05) in the tenofovir arm. In the tenofovir arm only, significant inverse correlations were observed between gp120-specific ADCC and gp120-antibody titres (r = −0.54; p = 0.009), and gp41-specific ADNP and gp41-specific antibody titres at 6 months post-infection (r = −0.50; p = 0.015). In addition, in the tenofovir arm, gp41-specific ADCC showed significant direct correlations between the compartments (r = 0.53; p = 0.045). Certain HIV-specific nNAb activities not only dominate specific immunological compartments but can also exhibit diverse functions within the same compartment. Our previous findings of increased HIV specific antibody detection and titres in women who used tenofovir gel, and the limited differences in nNAb activities between the arms, suggest that prior PrEP did not modulate these nNAb functions post-HIV seroconversion. Together these data provide insight into envelope-specific-nNAb Fc-mediated functions at the site of exposure which may inform on ensuing immunity during combination HIV prevention strategies including PrEP and HIV vaccines. |
| first_indexed | 2024-12-11T07:19:57Z |
| format | Article |
| id | doaj.art-71c1969aa4b74df88f67c6aa5d11bee3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T07:19:57Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-71c1969aa4b74df88f67c6aa5d11bee32022-12-22T01:16:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01274498755Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in WomenKimone Leigh Fisher0Jennifer M. Mabuka1Jennifer M. Mabuka2Aida Sivro3Aida Sivro4Sinaye Ngcapu5Sinaye Ngcapu6Jo-Ann Shelley Passmore7Jo-Ann Shelley Passmore8Farzana Osman9Bongiwe Ndlovu10Quarraisha Abdool Karim11Quarraisha Abdool Karim12Salim S. Abdool Karim13Salim S. Abdool Karim14Amy W. Chung15Cheryl Baxter16Cheryl Baxter17Derseree Archary18Derseree Archary19Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaDepartment of Medical Microbiology, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaDepartment of Medical Microbiology, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaInstitute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, and National Health Laboratory Service, Cape Town, South AfricaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United StatesCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United StatesDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, AustraliaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaDepartment of Public Health, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South AfricaDepartment of Medical Microbiology, University of KwaZulu-Natal, Durban, South AfricaThe RV144 HIV-vaccine trial highlighted the importance of envelope-specific non-neutralizing antibody (nNAb) Fc-mediated functions as immune correlates of reduced risk of infection. Since pre-exposure prophylaxis (PrEP) and HIV-vaccines are being used as a combination prevention strategy in at risk populations, the effects of PrEP on nNAb functions both mucosally and systemically remain undefined. Previous animal and human studies demonstrated reduced HIV-specific antibody binding avidity post-HIV seroconversion with PrEP, which in turn may affect antibody functionality. In seroconverters from the CAPRISA 004 tenofovir gel trial, we previously reported significantly higher detection and titres of HIV-specific binding antibodies in the plasma and genital tract (GT) that distinguished the tenofovir from the placebo arm. We hypothesized that higher HIV-specific antibody titres and detection reflected corresponding increased antibody-dependent neutrophil-mediated phagocytosis (ADNP) and NK-cell-activated antibody-dependent cellular cytotoxic (ADCC) activities. HIV-specific V1V2-gp70, gp120, gp41, p66, and p24 antibodies in GT and plasma samples of 48 seroconverters from the CAPRISA 004 tenofovir gel trial were tested for ADCP and ADCC at 3, 6- and 12-months post-HIV-infection. GT gp41- and p24-specific ADNP were significantly higher in the tenofovir than the placebo arm at 6 and 12 months respectively (p < 0.05). Plasma gp120-, gp41-, and p66-specific ADNP, and GT gp41-specific ADCC increased significantly over time (p < 0.05) in the tenofovir arm. In the tenofovir arm only, significant inverse correlations were observed between gp120-specific ADCC and gp120-antibody titres (r = −0.54; p = 0.009), and gp41-specific ADNP and gp41-specific antibody titres at 6 months post-infection (r = −0.50; p = 0.015). In addition, in the tenofovir arm, gp41-specific ADCC showed significant direct correlations between the compartments (r = 0.53; p = 0.045). Certain HIV-specific nNAb activities not only dominate specific immunological compartments but can also exhibit diverse functions within the same compartment. Our previous findings of increased HIV specific antibody detection and titres in women who used tenofovir gel, and the limited differences in nNAb activities between the arms, suggest that prior PrEP did not modulate these nNAb functions post-HIV seroconversion. Together these data provide insight into envelope-specific-nNAb Fc-mediated functions at the site of exposure which may inform on ensuing immunity during combination HIV prevention strategies including PrEP and HIV vaccines.https://www.frontiersin.org/article/10.3389/fimmu.2020.01274/fullFc-mediated activitytenofovirHIVwomenADCC–antibody dependent cellular cytotoxicityADNP |
| spellingShingle | Kimone Leigh Fisher Jennifer M. Mabuka Jennifer M. Mabuka Aida Sivro Aida Sivro Sinaye Ngcapu Sinaye Ngcapu Jo-Ann Shelley Passmore Jo-Ann Shelley Passmore Farzana Osman Bongiwe Ndlovu Quarraisha Abdool Karim Quarraisha Abdool Karim Salim S. Abdool Karim Salim S. Abdool Karim Amy W. Chung Cheryl Baxter Cheryl Baxter Derseree Archary Derseree Archary Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women Frontiers in Immunology Fc-mediated activity tenofovir HIV women ADCC–antibody dependent cellular cytotoxicity ADNP |
| title | Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women |
| title_full | Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women |
| title_fullStr | Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women |
| title_full_unstemmed | Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women |
| title_short | Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women |
| title_sort | topical tenofovir pre exposure prophylaxis and mucosal hiv specific fc mediated antibody activities in women |
| topic | Fc-mediated activity tenofovir HIV women ADCC–antibody dependent cellular cytotoxicity ADNP |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01274/full |
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