Browsing by Author "Laher, Fatima"

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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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    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, Zvavahera M.; Laher, Fatima; Dintwe, One; Muyoyeta, Monde; deCamp, Allan C.; He, Zonglin; Grunenberg, Nicole; Laher, Faatima, O.; Seaton, Kelly E.; Polakowski, Laura; Davis, Amanda S. W.; Maganga, Lucas; Baden, Lindsey R.; Mayer, Kenneth; Kalams, Spyros ; Keefer, Michael; Edupuganti, Srilatha; Rodriguez, Benigno; Frank, Ian; Scott, Hyman; Stranix-Chibanda, Lynda; Gurunathan, Sanjay; Koutsoukos, Marguerite; Van Der Meeren, Olivier; DiazGranados, Carlos A.; Paez, Carmen; Andersen-Nissen, Erica; Kublin, James; Corey, Lawrence ; Ferrari, Guido; Tomaras, Georgia; McElrath, Juliana M.
    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.