Browsing by Author "Polakowski L"

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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; ICAP at Columbia University, Eswatini Prevention Center, Mbabane, Eswatini.; 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.; University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA.; South African Medical Research Council, Isipingo Clinical Research Site, KwaZulu-Natal, South Africa.; Soweto - Kliptown Clinical Research Site, Soweto, South Africa.; Synergy Biomed Research Institute, East London, South Africa.; Qhakaza Mbokodo Research Clinic, Ladysmith, South Africa.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, USA.; COVID-19 Prevention Network, Seattle, USA.; Wits RHI University of the Witwatersrand, Johannesburg, South Africa.; TASK Eden, Western Cape, South Africa.; Synexus Stanza Clinical Research Centre Clinical Research Site, Pretoria, South Africa.; TASK Central, Cape Town, South Africa.; Department of Global Health, University of Washington, Seattle, USA.; KwaZulu-Natal Research Innovation & Sequencing Platform, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; Moi University Clinical Research Centre, Eldoret, Kenya.; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.; PHOENIX Pharma (Pty) Ltd, Port Elizabeth, South Africa.; Kisumu Clinical Research Site, Kisumu, Kenya.; South African Medical Research Council, Pretoria, South Africa.; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, South Africa.; FAMCRU Family Clinical Research Unit, Cape Town, South Africa.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Joint Clinical Research Centre, Lubowa, Uganda.; MU-JHU Research Collaboration Clinical Research Site, Kampala, Uganda.; Johns Hopkins Research Project, Blantyre, Malawi.; Center for HIV/AIDS Vaccine Immunology, Duke University School of Medicine, Durham, NC, USA.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.; Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.; The Aurum Institute, Rustenburg Clinical Research Site, Rustenburg, South Africa.; Synexus Helderberg, Cape Town, South Africa.; The Aurum Institute, Klerksdorp Clinical Research Site, Klerksdorp, South Africa.; MERC Kempton, Kempton, South Africa.; Malawi Clinical Research Site, Lilongwe, Malawi.; MERC Welkom, Welkom, South Africa.; Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa.; Hutchinson Centre Research Institute of South Africa, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.; CFHRZ - Ndola Clinical Research Site, Ndola, Zambia.; Department of Medicine, University of Cape Town, Cape Town, South Africa.; University of Cape Town Lung Institute Clinical Research Site, Cape Town, South Africa.; Josha Research Clinical Research Site, Bloemfontein, South Africa.; MERC Middelburg, Middelburg, South Africa.; Centre for Epidemic Response & Innovation, Stellenbosch, South Africa.; Clinical Trials Research Centre, University of Zimbabwe, Harare, Zimbabwe.; Kombewa Clinical Research Site, Kisumu, Kenya.; Maseno University School of Medicine, Kenya.; UNC Global Projects/Kamwala District Health Centre, Lusaka, Zambia.; UVRI-IAVI HIV Vaccine Program Ltd. Clinical Research Site, Entebbe, Uganda.; Botswana Harvard AIDS Institute, Gaborone, Botswana.; PHRU Matlosana Clinical Research Site, Klerksdorp, South Africa.; MeCRU Clinical Research Site, Pretoria, South Africa.; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, USA.; Tembisa Clinic 4, Gauteng, South Africa.; Blantyre Clinical Research Site, Blantyre, Malawi.; CFHRZ Clinical Research Site, Lusaka, Zambia.; Newtown Clinical Research, Johannesburg, South Africa.; Clinical HIV Research Unit/Helen Joseph Clinical Research Site, Johannesburg, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Tongaat Clinical Research Site, KwaZulu-Natal, South Africa.; 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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    Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120.
    (2024-Aug-16) Chirenje ZM; Laher F; Dintwe O; Muyoyeta M; deCamp AC; He Z; Grunenberg N; Laher Omar F; Seaton KE; Polakowski L; Woodward Davis AS; Maganga L; Baden LR; Mayer K; Kalams S; Keefer M; Edupuganti S; Rodriguez B; Frank I; Scott H; Stranix-Chibanda L; Gurunathan S; Koutsoukos M; Van Der Meeren O; DiazGranados CA; Paez C; Andersen-Nissen E; Kublin J; Corey L; Ferrari G; Tomaras G; McElrath MJ; Faculty of Medicine and Health Science, University of Zimbabwe Clinical Trials Research Centre, University of Zimbabwe, Harare, Zimbabwe.; Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts, USA.; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Centre for Infectious Diseases Research in Zambia, Livingstone, Zambia.; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals, Cleveland Medical Center, Cleveland, Ohio, USA.; Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Sanofi Pasteur, Swiftwater, Pennsylvania, USA.; Center for Human Systems Immunology, Duke University School of Medicine, Durham, North Carolina, USA.; GSK, Wavre, Belgium.; Department of Medicine, Emory University, Atlanta, Georgia, USA.; Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, California, USA.; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.; SanFrancisco Department of Public Health, San Francisco, California, USA.; GSK, Rixensart, Belgium.; Cape Town HIV Vaccine Trials Network Immunology Laboratory, Cape Town, South Africa.; Department of Medicine, University of Rochester, Rochester, NewYork, USA.; School of Medicine, University of Pennsylvania, Philadelphia, USA.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; National Institute for Medical Research-Mbeya Medical Research Centre, Mbeya, Tanzania.; Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; The Fenway Institute, Fenway Health, Boston, Massachusetts, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.