| Autor: |
Avi Kenny, Janine van Duijn, One Dintwe, Jack Heptinstall, Randy Burnham, Sheetal Sawant, Lu Zhang, Dieter Mielke, Sharon Khuzwayo, Faatima Laher Omar, Sherry Stanfield-Oakley, Taylor Keyes, Brooke Dunn, Derrick Goodman, Youyi Fong, David Benkeser, Rodger Zou, John Hural, Ollivier Hyrien, Michal Juraska, Alex Luedtke, Lars van der Laan, Elena E. Giorgi, Craig Magaret, Lindsay N. Carpp, Laura Pattacini, Tom van de Kerkhof, Bette Korber, Wouter Willems, Leigh H. Fisher, Hanneke Schuitemaker, Edith Swann, James G. Kublin, Maria G. Pau, Susan Buchbinder, Frank Tomaka, Steven Nijs, Ludo Lavreys, Huub C. Gelderblom, Lawrence Corey, Kathryn Mngadi, Glenda E. Gray, Erica Borducchi, Jenny Hendriks, Kelly E. Seaton, Susan Zolla-Pazner, Dan H. Barouch, Guido Ferrari, Stephen C. De Rosa, M Juliana McElrath, Erica Andersen-Nissen, Daniel J. Stieh, Georgia D. Tomaras, Peter B. Gilbert, Jon Allagappen, Jessica Andriesen, Alison Ayres, Saman Baral, Linda-Gail Bekker, Asiphe Besethi, Caroline Borremans, Esmee Braams, Caroline Brackett, William Brumskine, Roma Chilengi, Rachel Choi, Thozama Dubula, Jaiden Seongmi Dumas, Radhika Etikala, Zelda Euler, Sarah Everett, Nigel Garrett, Huub Gelderblom, Katherine Gill, Kevin Gillespie, Dimitri Goedhart, Erik Goosmann, Shannon Grant, Ellie Hands, Barton Haynes, Bronwill Herringer, Zaheer Hoosain, Mina Hosseinipour, Portia Hunidzarira, Julia Hutter, Mubiana Inambao, Craig Innes, William Kilembe, Philippus Kotze, Sheena Kotze, Fatima Laher, Imre Laszlo, Erica Lazarus, Hua-Xin Liao, Yong Lin, Helen Lu, Judith Lucas, Mookho Malahleha, Tara McNair, Peter Meerts, Zinhle Mgaga, Mahlodi Montlha, Boitumelo Mosito, Andrew Moultrie, Sarah Mudrak, Valérie Oriol-Mathieu, Marcella Sarzotti-Kelsoe, Matson Tso Mathebula, Mitch Matoga, Rachael McClennen, Pamela Mda, Vimla Naicker, Logashvari Naidoo, Cindy-Ann Okkers, Saleha Omarjee, Hella Pasmans, Tricia Philip, Abraham Pinter, Annah Pitsi, Ornelia Ramos, April Randhawa, Sanne Roels, Shamiska Rohith, Lucy Rutten, Jerald Sadoff, Gabriela Salinas, Yvonne Salzgeber, Lorenz Scheppler, Katharine Schwedhelm, Nicolette Schuller, Angelina Sharak, Carrie Sopher, Terence Tafatatha, Simbarashe G. Takuva, Chan Tang, An Vandebosch, Edna Viegas, Valentin Voillet, Frank Wegmann, Mo Weijtens, Stephany Wilcox, Anthony Williams, Chenchen Yu, Pei-Chun Yu, Olive Yuan, Xuehan Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 108, Iss , Pp 105320- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2024.105320 |
| Popis: |
Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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