Sufia Dadabhai, Taraz Samandari, Bo Zhang, Aaron Hudson, Nonhlanhla Mkhize, Asa Tapley, Jessica Andriesen, Penny Moore, Zvavahera Chirenje, Peter Elyanu, Joseph Makhema, Ethel Kamuti, Harriet Nuwagaba-Biribonwoha, Jin Kee, Jiani Hu, Katekani Baloyi-Oseh, Parth Shah, Kentse Khuto, Maurine Miner, Richard Lessells, Sinethemba Bhebhe, Tandile Modise, Haajira Kaldine, Azwidihwi Takalani, Margaret Yacovone, John Hural, Leigh Fisher, Craig Magaret, Florence Aweyo, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Katherine Gill, Mina Hosseinipour, Steve Innes, Priya Kassim, Emmanuel Kafulafula, Fatima Laher, Nelly Mandona, Moelo Malahleha, Vongane Maluleke, Matsontso Mathebula, Grace Mboya, Essack Mitha, Kathy Mngadi, Pamela Mda, Tumelo Moloantoa, Nivashnee Naicker, Vimla Naicker, Annet Nanvubya, Maphoshane Nchabeleng, Walter Otieno, Elsje Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Mohammed Tayob, Deo Wabwire, Myron Cohen, M Juliana McElrath, Erica Andersen-Nissen, Guido Ferrari, James Kublin, Linda Gail-Bekker, Peter Gilbert, Nyaradzo Mgodi, Philip Kotze, Yunda Huang, Nigel Garrett, Glenda Gray, Lawrence Corey
The relative efficacy, safety, and immunogenicity of monovalent mRNA-1273 (ancestral WA1) versus bivalent mRNA-1273.222 (ancestral plus omicron BA.4/BA.5) boosting have not been studied prospectively where HIV and SARS-CoV-2 seroprevalence are high. CoVPN 3008 (NCT05168813) was a randomized, double-blinded trial in seven African countries during omicron waves, enrolling people with HIV (PWH) or comorbidities associated with severe COVID-19 who had previously received mRNA-1273. Participants were randomized 1:1 to intramuscular monovalent or bivalent booster and routinely PCR-tested for SARS-CoV-2. Between 10/2022 and 03/2023, 3,988 participants (3,086 PWH) received bivalent (n = 2012) or monovalent (n = 1976) booster. By month 12, 293 COVID-19 cases and 221 asymptomatic infections occurred, including one severe case. COVID-19 rates did not differ between arms (hazard ratio [HR] 0.92, 95% CI 0.73-1.15, P = 0.45). Combined COVID-19 and asymptomatic infection was 15% lower with the bivalent (239 vs. 275; HR 0.85, 0.71-1.01, P = 0.07), and asymptomatic infection alone was 24% lower (HR 0.76, 0.59-1.00, P = 0.05). Neutralizing antibody titers to BA.4/5 and XBB.1.5, measured in 100 PWH per arm, boosted higher in bivalent recipients (P = 0.026 and 0.002). Adverse events were similar. In predominantly PWH, the bivalent booster was well tolerated, elicited superior immunogenicity against omicron variants, and appeared to protect against asymptomatic infection but not COVID-19.