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

• Type of Material: Article
• Authors: Glenda E Gray, Fred Hutchinson Cancer Research Center, Seattle; Linda-Gail Bekker, University of Cape Town; Fatima Laher, University of Witwatersrand; Mookho Malahleha, Setshaba Research Centre, Soshanguve; Mary Allen, Fred Hutchinson Cancer Research Center, Seattle; Zoe Moodie, Fred Hutchinson Cancer Research Center, Seattle; Nicole Grunenberg, Fred Hutchinson Cancer Research Center, Seattle; Yunda Huang, Fred Hutchinson Cancer Research Center, Seattle; Doug Grove, Fred H Fred Hutchinson Cancer Research Center, Seattle; Brittany Prigmore, Fred Hutchinson Cancer Research Center, Seattle; Jia J Kee, Fred Hutchinson Cancer Research Center, Seattle; David Benkeser, Emory University; John Hural, Fred Hutchinson Cancer Research Center, Seattle; Craig Innes, Aurum Institute, South Africa; Erica Lazarus, University of Witwatersrand; Graeme Meintjes, University of Cape Town; Nivashnee Naicker, University of Kwazulu Natal; Dishiki Kalonji, South African Medical Research Council; Maphoshane Nchabeleng, Sefako Mkgatho Health Sciences University; Modulakgotla Sebe, Aurum Institute, South Africa; Nishanta Singh, South African Medical Research Council; Philip Kotze, Qhakaza Mbokodo Research Clinic; Sheetal Kassim, University of Cape Town; Thozama Dubula, Walter Sisulu University; Vimla Naicker, South African Medical Research Council; William Brumskine, Aurum Institute, South Africa; Cleon N Ncayiya, University of Cape Town; Amy M Ward, University of Cape Town; Nigel Garrett, University of Kwazulu Natal; Grisha Kistnasami, South African Medical Research Council; Zakir Gaffoor, South African Medical Research Council; Pearl Selepe, Aurum Institute, South Africa; Philisiwe B Makhoba, Qhakaza Mbokodo Res Clin; Matsontso P Mathebula, Sefako Mkgatho Health Sciences University; Pamela Mda, Walter Sisulu University; Tania Adonis, Aurum Institute, South Africa; Katlego S Mapetla, Setshaba Research Centre; Bontle Modibedi, University of Witwatersrand; Tricia Philip, University of Witwatersrand; Gladys Kobane, Aurum Institute, South Africa; Carter Bentley, Fred Hutchinson Cancer Research Center, Seattle; Shelly Ramirez, Fred Hutchinson Cancer Research Center, Seattle; Simbarashe Takuva, Fred Hutchinson Cancer Research Center, Seattle; Megan Jones, Fred Hutchinson Cancer Research Center, Seattle; Mpho Sikhosana, Fred Hutchinson Cancer Research Center, Seattle; Millicent Atujuna, University of Cape Town; Michele Andrasik, Fred Hutchinson Cancer Research Center, Seattle; Nima S Hejazi, University of California Berkeley; Adrian Puren, National Health Laboratory Service, Johannesburg; Lubbe Wiesner, University of Cape Town; Sanjay Phogat, Sanofi Pasteur, Swiftwater; Carlos Diaz Granados, Sanofi Pasteur, Swiftwater; Marguerite Koutsoukos, GlaxoSmithKline; Olivier van der Meeren, GlaxoSmithKline; Susan W Barnett, GSK Vaccines; Niranjan Kanesa-Thasan, GlaxoSmithKline Vaccines; James G Kublin, Fred Hutchinson Cancer Research Center, Seattle; Juliana McElrath, Fred Hutchinson Cancer Research Center, Seattle; Peter B Gilbert, Fred Hutchinson Cancer Research Center, Seattle; Holly Janes, Fred Hutchinson Cancer Research Center, Seattle; Lawrence Corey, Fred Hutchinson Canc Res Ctr Fred Hutchinson Cancer Research Center, Seattle
• Language: English
• Date: 2021-03-25
• Publisher: MASSACHUSETTS MEDICAL SOC
• Publication Version: Final Published Version
• Copyright Statement: © 2021, Massachusetts Medical Society
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1056/NEJMoa2031499
• Title of Journal or Parent Work: NEW ENGLAND JOURNAL OF MEDICINE
• Volume: 384
• Issue: 12
• Start Page: 1089
• End Page: 1100
• Grant/Funding Information: Funding was provided to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline Biologicals SA) by NIAID (HHSN272201300033C//HHSN272201600012C) for the selection and process development of the two gp120 envelope proteins TV1.C and 1086.C, and by the Bill & Melinda Gates Foundation Global Health Grant OPP1017604 and NIAID for the manufacture and release of the gp120 clinical grade material. GlaxoSmithKline Biologicals SA has contributed financially to PrEP provision. Funding was also provided by NIAID U.S. Public Health Service Grants UM1 AI068614 [LOC: HIV Vaccine Trials Network], UM1 AI068635 [HVTN SDMC FHCRC], and UM1 AI068618 [HVTN Laboratory Center FHCRC]. The South African Medical Research Council supported SAMRC affiliated research sites.
• Keywords: Science & Technology; General & Internal Medicine; Life Sciences & Biomedicine; Medicine, General & Internal

Abstract

BACKGROUND A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS In this phase 2b–3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120–MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P=0.84). CONCLUSIONS The ALVAC–gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.