Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120/MF59 in Adults

BACKGROUND: A safe, effective vaccine is essential to end HIV. A canarypox/protein HIV vaccine regimen showed modest efficacy at reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus demonstrated potent humoral and cellular responses in a Phase 1/2a trial and triggered a P...

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Detalles Bibliográficos
Autores principales: Gray, Glenda E, Bekker, Linda-Gail, Laher, Fatima, Malahleha, Mookho, Allen, Mary, Moodie, Zoe, Grunenberg, Nicole, Huang, Yunda, Grove, Doug, Prigmore, Brittany, Kee, Jia J., Benkeser, David, Hural, John, Innes, Craig, Lazarus, Erica, Meintjes, Graeme, Naicker, Nivashnee, Kalonji, Dishiki, Nchabeleng, Maphoshane, Sebe, Modulakgotla, Singh, Nishanta, Kotze, Philip, Kassim, Sheetal, Dubula, Thozama, Naicker, Vimla, Brumskine, William, Ncayiya, Cleon N, Ward, Amy M, Garrett, Nigel, Kistnasami, Girisha, Gaffoor, Zakir, Selepe, Pearl, Makhoba, Philisiwe B, Mathebula, Matsontso P, Mda, Pamela, Adonis, Tania, Mapetla, Katlego S, Modibedi, Bontle, Philip, Tricia, Kobane, Gladys, Bentley, Carter, Ramirez, Shelly, Takuva, Simbarashe, Jones, Megan, Sikhosana, Mpho, Atujuna, Millicent, Andrasik, Michele, Hejazi, Nima S., Puren, Adrian, Wiesner, Lubbe, Phogat, Sanjay, Diaz Granados, Carlos, Koutsoukos, Marguerite, Van Der Meeren, Olivier, Barnett, Susan W., Kanesa-thasan, Niranjan, Kublin, James G., McElrath, M. Juliana, Gilbert, Peter B., Janes, Holly, Corey, Lawrence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Massachusetts Medical Society 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888373/
https://www.ncbi.nlm.nih.gov/pubmed/33761206
http://dx.doi.org/10.1056/NEJMoa2031499
Descripción
Sumario:BACKGROUND: A safe, effective vaccine is essential to end HIV. A canarypox/protein HIV vaccine regimen showed modest efficacy at reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus demonstrated potent humoral and cellular responses in a Phase 1/2a trial and triggered a Phase 2b/3 double-blinded trial to assess the safety and efficacy of this regimen in South Africa. METHODS: We enrolled and randomized 5,404 healthy, HIV-uninfected 18-35-year olds at 14 sites to vaccine (2,704 participants) or placebo (2,700 participants) between 26 October 2016 and 21 June 2019. The vaccine regimen consisted of two ALVAC-HIV (vCP2438) (expressing HIV-1 subtype C env, clade B gp41, gag and pro) immunizations at months 0 and 1, with booster immunizations of ALVAC-HIV plus bivalent subtype C gp120 protein/MF59 adjuvant at months 3, 6, 12 and 18. Efficacy was evaluated by HIV testing every 3 months. RESULTS: In January 2020, pre-specified non-efficacy criteria were met at an interim analysis; further vaccinations were subsequently halted. The vaccines were safe and well-tolerated in the study population (median age 24, 70% female-sex-at-birth). Over the primary 24-month follow-up, there were 133 infections among placebo recipients and 138 among vaccinees (hazard ratio = 1.02; 95%CI, 0.81-1.30; P=0.84). Pre-specified subgroup analyses demonstrated no difference in efficacy by sex or when restricting to follow-up post-4(th) vaccination, and no difference amongst female-sex-at-birth by age, BMI, prevalent STIs, behavioral risk score or region. CONCLUSIONS: The ALVAC/gp120 regimen did not prevent HIV infection in South Africans despite prior evidence of immunogenicity. ClinicalTrials.gov (NCT02968849)

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