Browsing by Author "Innes C"

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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 N; Tapley A; Hudson A; Dadabhai S; Zhang B; Mgodi NM; Andriesen J; Takalani A; Fisher LH; Kee JJ; Magaret CA; Villaran M; Hural J; Andersen-Nissen E; Ferarri G; Miner MD; Le Roux B; Wilkinson E; Lessells R; de Oliveira T; Odhiambo J; Shah P; Polakowski L; Yacovone M; Samandari T; Chirenje Z; Elyanu PJ; Makhema J; Kamuti E; Nuwagaba-Biribonwoha H; Badal-Faesen S; Brumskine W; Coetzer S; Dawson R; Delany-Moretlwe S; Diacon AH; Fry S; Gill KM; Ebrahim Hoosain ZA; Hosseinipour MC; Inambao M; Innes C; Innes S; Kalonji D; Kasaro M; Kassim P; Kayange N; Kilembe W; Laher F; Malahleha M; Maluleke VL; Mboya G; McHarry K; Mitha E; Mngadi K; Mda P; Moloantoa T; Mutuluuza CK; Naicker N; Naicker V; Nana A; Nanvubya A; Nchabeleng M; Otieno W; Potgieter EL; Potloane D; Punt Z; Said J; Singh Y; Tayob MS; Vahed Y; Wabwire DO; McElrath MJ; Kublin JG; Bekker LG; Gilbert PB; Corey L; Gray GE; Huang Y; Kotze P; Botswana Harvard AIDS Institute, Gaborone, Botswana.; ICAP at Columbia University, Eswatini Prevention Center, Mbabane, Eswatini.; CFHRZ Clinical Research Site, Lusaka, Zambia.; Synergy Biomed Research Institute, East London, South Africa.; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda.; Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; MERC Middelburg, Middelburg, South Africa.; UVRI-IAVI HIV Vaccine Program Ltd. Clinical Research Site, Entebbe, Uganda.; Tongaat Clinical Research Site, KwaZulu-Natal, South Africa.; Kombewa Clinical Research Site, Kisumu, Kenya.; South African Medical Research Council, Isipingo Clinical Research Site, KwaZulu-Natal, South Africa.; Department of Medicine, University of Cape Town, Cape Town, South Africa.; Malawi Clinical Research Site, Lilongwe, Malawi.; Kisumu Clinical Research Site, Kisumu, Kenya.; Clinical Trials Research Centre, University of Zimbabwe, Harare, Zimbabwe.; TASK Eden, Western Cape, South Africa.; Nelson Mandela Academic Clinical Research Unit Clinical Research Site, Mthatha, South Africa.; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, USA.; Tembisa Clinic 4, Gauteng, South Africa.; Johns Hopkins Research Project, Blantyre, Malawi.; Department of Global Health, University of Washington, Seattle, USA.; University of Cape Town Lung Institute Clinical Research Site, Cape Town, South Africa.; Joint Clinical Research Centre, Lubowa, Uganda.; CFHRZ - Ndola Clinical Research Site, Ndola, Zambia.; Synexus Stanza Clinical Research Centre Clinical Research Site, Pretoria, South Africa.; KwaZulu-Natal Research Innovation & Sequencing Platform, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Hutchinson Centre Research Institute of South Africa, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.; University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA.; UNC Global Projects/Kamwala District Health Centre, Lusaka, Zambia.; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, South Africa.; South African Medical Research Council, Pretoria, South Africa.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.; Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa.; The Aurum Institute, Rustenburg Clinical Research Site, Rustenburg, South Africa.; Centre for Epidemic Response & Innovation, Stellenbosch, South Africa.; Blantyre Clinical Research Site, Blantyre, Malawi.; MeCRU Clinical Research Site, Pretoria, South Africa.; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.; Center for HIV/AIDS Vaccine Immunology, Duke University School of Medicine, Durham, NC, USA.; MERC Welkom, Welkom, South Africa.; Moi University Clinical Research Centre, Eldoret, Kenya.; COVID-19 Prevention Network, Seattle, USA.; The Aurum Institute, Klerksdorp Clinical Research Site, Klerksdorp, South Africa.; TASK Central, Cape Town, South Africa.; PHRU Matlosana Clinical Research Site, Klerksdorp, South Africa.; Synexus Helderberg, Cape Town, South Africa.; FAMCRU Family Clinical Research Unit, Cape Town, South Africa.; Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.; Soweto - Kliptown Clinical Research Site, Soweto, South Africa.; Clinical HIV Research Unit/Helen Joseph Clinical Research Site, Johannesburg, South Africa.; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, USA.; Qhakaza Mbokodo Research Clinic, Ladysmith, South Africa.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.; Maseno University School of Medicine, Kenya.; MERC Kempton, Kempton, South Africa.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, USA.; PHOENIX Pharma (Pty) Ltd, Port Elizabeth, South Africa.; Wits RHI University of the Witwatersrand, Johannesburg, South Africa.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; MU-JHU Research Collaboration Clinical Research Site, Kampala, Uganda.; Newtown Clinical Research, Johannesburg, South Africa.; Josha Research Clinical Research Site, Bloemfontein, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    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 MC; Innes C; Naidoo S; Mann P; Hutter J; Ramjee G; Sebe M; Maganga L; Herce ME; deCamp AC; Marshall K; Dintwe O; Andersen-Nissen E; Tomaras GD; Mkhize N; Morris L; Jensen R; Miner MD; Pantaleo G; Ding S; Van Der Meeren O; Barnett SW; McElrath MJ; Corey L; Kublin JG; National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.; NIMR-Mbeya Medical Research Center, Mbeya, Tanzania.; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Aurum Institute, Klerksdorp, South Africa.; GSK Vaccines, Rixensart, Belgium.; Cape Town HVTN Immunology Laboratory, Cape Town, South Africa.; EuroVacc Foundation, Lausanne, Switzerland.; UNC Project-Malawi, Lilongwe, Malawi.; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Aurum Institute, Tembisa, South Africa.; HIV Prevention Research Unit, South African Medical Research Council, Durban, South Africa.; GSK Vaccines, Cambridge, Massachusetts, USA.; Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    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).