Browsing by Author "Innes, Craig"

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    Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.
    (2025-Feb) Garrett, Nigel; Tapley, Asa; Hudson, Aaron; Dadabhai, Sufia; Zhang, Bo; Mgodi, Nyaradzo M.; Andriesen, Jessica; Takalani, Azwidihwi; Fisher, Leigh H.; Kee, Jia J.; Magaret, Craig A.; Villaran, Manuel; Hural, John; Andersen-Nissen, Erica; Ferarri, Guido; Miner, Maurine D.; Le Roux, Bert; Wilkinson, Eduan; Lessells, Richard; de Oliveira, Tulio; Odhiambo, Jackline; Shah, Parth; Polakowski, Laura; Yacovone, Margaret; Samandari, Taraz; Chirenje, Zvavahera ; Elyanu, Peter J.; Makhema, Joseph; Kamuti, Ethel; Nuwagaba-Biribonwoha, Harriet; Badal-Faesen, Sharlaa; Brumskine, William; Coetzer, Soritha; Dawson, Rodney; Delany-Moretlwe, Sinead; Diacon, Andreas H.; Fry, Samantha; Gill, Katherine M.; Hoosain, Zaheer A. E.; Hosseinipour, Mina C.; Inambao, Mubiana; Innes, Craig; Innes, Steve; Kalonji, Dishiki; Kasaro, Margaret; Kassim, Priya; Kayange, Noel; Kilembe, William; Laher, Fatima; Malahleha, Moelo ; Maluleke, Vongane L.; Mboya, Grace; McHarry, Kirsten; Mitha, Essack; Mngadi, Kathryn ; Mda, Pamela; Moloantoa, Tumelo; Mutuluuza, Cissy K.; Naicker, Nivashnee; Naicker, Vimla; Nana, Anusha; Nanvubya, Annet; Nchabeleng, Maphoshane; Otieno, Walter; Potgieter, Elsje L.; Potloane, Disebo; Punt, Zelda; Said, Jamil; Singh, Yasmine; Tayob, Mohammed S.; Vahed, Yacoob; Wabwire, Deo O.; McElrath, Juliana M.; Kublin, James G.; Bekker, Linda-Gail ; Gilbert, Peter B.; Corey, Lawrence; Gray, Glenda E.; Huang, Yunda; Kotze, Philip
    BACKGROUND: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. METHODS: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023. FINDINGS: Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days. INTERPRETATION: Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants. FUNDING: National Institute of Allergy and Infectious Diseases.
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    Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.
    (2021-Jan-23) Hosseinipour, Mina C.; Innes, Craig; Naidoo, Sarita; Mann, Philipp; Hutter, Julia; Ramjee, Gita; Sebe, Modulakgotla; Maganga, Lucas; Herce, Michael E.; deCamp, Allan C.; Marshall, Kyle; Dintwe, One; Andersen-Nissen, Erica; Tomaras, Georgia D.; Mkhize, Nonhlanhla; Morris, Lynn; Jensen, Ryan; Miner, Maurine D.; Pantaleo, Giuseppe; Ding, Song; Van Der Meeren, Olivier; Barnett, Susan W.; McElrath, Juliana M. ; Corey, Lawrence; Kublin, James G.
    BACKGROUND: The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. METHODS: In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1-uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. RESULTS: All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61). CONCLUSIONS: Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. CLINICAL TRIALS REGISTRATION: South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27-0715-4917) and ClinicalTrials.gov (NCT02997969).