School of Public Health (Journal Articles)

Permanent URI for this collectionhttps://hdl.handle.net/10539/37879

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Author: search.filters.author.Madhi, Shabir A.Start date: 2020

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    Comparable safety and non‑inferior immunogenicity of the SARS‑CoV‑2 mRNA vaccine candidate PTX‑COVID19‑B and BNT162b2 in a phase 2 randomized, observer‑blinded study
    (Nature Research, 2024) Madhi, Shabir A.; Tran, Richard; Martin‑Orozco, Natalia; Panicker, Rajesh Krishnan Gopalakrishna; Pastrak, Aleksandra; Reiter, Lawrence; Grefrath, Johann; Zidel, Bian; Ostrowski, Mario; Gommerman, Jennifer; Cooper, Curtis
    In the aftermath of the COVID-19 pandemic, the evolution of the SARS-CoV-2 into a seasonal pathogen along with the emergence of new variants, underscores the need for dynamic and adaptable responses, emphasizing the importance of sustained vaccination strategies. This observer-blind, double-dummy, randomized immunobridging phase 2 study (NCT05175742) aimed to compare the immunogenicity induced by two doses of 40 μg PTX-COVID19-B vaccine candidate administered 28 days apart, with the response induced by two doses of 30 µg Pfzer-BioNTech COVID-19 vaccine (BNT162b2), administered 21 days apart, in Nucleocapsid-protein seronegative adults 18–64 years of age. Both vaccines were administrated via intramuscular injection in the deltoid muscle. Two weeks after the second dose, the neutralizing antibody (NAb) geometric mean titer ratio and seroconversion rate met the non-inferiority criteria, successfully achieving the primary immunogenicity endpoints of the study. PTX-COVID19-B demonstrated similar safety and tolerability profle to BNT162b2 vaccine. The lowest NAb response was observed in subjects with low-to-undetectable NAb at baseline or no reported breakthrough infection. Conversely, participants who experienced breakthrough infections during the study exhibited higher NAb titers. This study also shows induction of cell-mediated immune (CMI) responses by PTX-COVID19-B. In conclusion, the vaccine candidate PTX-COVID19-B demonstrated favourable safety profle along with immunogenicity similar to the active comparator BNT162b2 vaccine.
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    T‑cell responses to ancestral SARS‑CoV‑2 and Omicron variant among unvaccinated pregnant and postpartum women living with and without HIV in South Africa
    (Nature Research, 2024-09) Madhi, Shabir A.; McMahon, William C.; Kwatra, Gaurav; Izu, Alane; Jones, Stephanie A.; Mbele, Nkululeko J.; Jafta, Nwabisa; Lala, Rushil; Shalekof, Sharon; Tiemessen, Caroline T.; Nunes, Marta C.
    SARS-CoV-2 cell-mediated immunity remains understudied during pregnancy in unvaccinated Black African women living with HIV (WLWH) from low- and middle-income countries. We investigated SARS-CoV-2-specifc T-cell responses 1 month following infection in 24 HIV-uninfected women and 15 WLWH at any stage during pregnancy or postpartum. The full-length spike (FLS) glycoprotein and nucleocapsid (N) protein of wild-type (WT) SARS-CoV-2, as well as mutated spike protein regions found in the Omicron variant (B.1.1.529) were targeted by flow cytometry. WT-specific CD4+and CD8+T cells elicited similar FLS- and N-specific responses in HIV-uninfected women and WLWH. SARS-CoV 2-specifc T-lymphocytes were predominantly TNF-α monofunctional in pregnant and postpartum women living with and without HIV, with fever cells producing either IFN-γ or IL-2. Furthermore, T-cell responses were unaffected by Omicron-specific spike mutations as similar responses between Omicron and the ancestral virus were detected for CD4+ and CD8+ T cells. Our results collectively demonstrate comparable T-cell responses between WLWH on antiretroviral therapy and HIV-uninfected pregnant and postpartum women who were naïve to Covid-19 vaccination. Additionally, we show that T cells from women infected with the ancestral virus, Beta variant (B.1.351), or Delta variant (B.1.617.2) can cross-recognize Omicron, suggesting an overall preservation of T-cell immunity.