Browsing by Author "Kamuti E"

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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
    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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    Safety, tolerability, and immunogenicity of an oral inactivated ETEC vaccine (ETVAX®) with dmLT adjuvant in healthy adults and children in Zambia: An age descending randomised, placebo-controlled trial.
    (2023-Nov-02) Sukwa N; Mubanga C; Hatyoka LM; Chilyabanyama ON; Chibuye M; Mundia S; Munyinda M; Kamuti E; Siyambango M; Badiozzaman S; Bosomprah S; Carlin N; Kaim J; Sjöstrand B; Simuyandi M; Chilengi R; Svennerholm AM
    BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is an important cause of moderate to severe diarrhoea in children for which there is no licensed vaccine. We evaluated ETVAX®, an oral, inactivated ETEC vaccine containing four E. coli strains over-expressing the major colonization factors CFA/I, CS3, CS5, and CS6, a toxoid (LCTBA) and double mutant heat-labile enterotoxin (dmLT) adjuvant for safety, tolerability, and immunogenicity. METHODS: A double-blind, placebo-controlled, age-descending, dose-finding trial was undertaken in 40 adults, 60 children aged 10-23 months, and 146 aged 6-9 months. Adults received one full dose of ETVAX® and children received 3 doses of either 1/4 or 1/8 dose. Safety was evaluated as solicited and unsolicited events for 7 days following vaccination. Immunogenicity was assessed by evaluation of plasma IgA antibody responses to CFA/I, CS3, CS5, CS6, and LTB, and IgG responses to LTB. RESULTS: Solicited adverse events were mostly mild or moderate with only 2 severe fever reports which were unrelated to the vaccine. The most common events were abdominal pain in adults (26.7 % in vaccinees vs 20 % in placebos), and fever in children aged 6-9 months (44 % vs 54  %). Dosage, number of vaccinations and decreasing age had no influence on severity or frequency of adverse events. The vaccine induced plasma IgA and IgG responses against LTB in 100 % of the adults and 80-90 % of the children. In the 6-23 months cohort, IgA responses to more than 3 vaccine antigens after 3 doses determined as ≥2-fold rise was significantly higher for 1/4 dose compared to placebo (56.7 % vs 27.2 %, p = 0.01). In the 6-9 months cohort, responses to the 1/4 dose were significantly higher than 1/8 dose after 3 rather than 2 doses. CONCLUSION: ETVAX® was safe, tolerable, and immunogenic in Zambian adults and children. The 1/4 dose induced significantly stronger IgA responses and is recommended for evaluation of protection in children. CLINICAL TRIALS REGISTRATION: The trial is registered with the Pan African Clinical Trials Registry (PACTR Ref. 201905764389804) and a description of this clinical trial is available on: https://pactr.samrc.ac.za/Trial Design.