Browsing by Author "Madhi, Shabir A."

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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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    Factors influencing access of pregnant women and their infants to their local healthcare system: a prospective, multicentre, observational study
    (BMC, 2018) Madhi, Shabir A.; Rivera, Luis M.; Sáez-Llorens, Xavier; Menéndez, Clara; Carrim-Ganey, Nazira; Cotton, Mark F.; Katzman, Darren; Luttig, Mariëtha M.; Candelario, Rosalba; Baker, Sherryl; Roychoudhury, Mahua
    Background: The successful implementation of maternal vaccination relies on results of clinical trials, considering the prenatal and postnatal attendance at selected healthcare institutions. This study evaluated factors influencing maternal/infant access to healthcare facilities to identify potential barriers to participation in future clinical trials on maternal vaccination. Methods: In this prospective, multi-centre, observational study, pregnant women (N = 3243) were enrolled at ten sites across Panama, the Dominican Republic, South Africa, and Mozambique between 2012 and 2014. They completed questionnaires at enrolment, delivery, and infant follow-up (90 days post-partum) visits, including questions on transportation, phone accessibility, alternative childcare, gestational age at enrolment, delivery location, and health status of their infant. Logistic regression was used to identify factors significantly associated with return to study site for delivery or infant follow-up visits. Results: Among 3229 enrolled women with delivery information, 63.6% (range across sites: 25.3–91.5%) returned to study site for delivery. Older women and those at later gestational age at enrolment were more likely to deliver at the study site. While heterogeneities were observed at site level, shorter travel time at delivery and increased transportation costs at enrolment were associated with increased likelihood of women returning to study site for delivery. Among 3145 women with live-born infants, 3077 (95.3%) provided 90-day follow-up information; of these, 68.9% (range across sites: 25.6–98.9%) returned to study site for follow-up visits. Women with other children and with lower transportation costs at delivery were more likely to return to study site for follow-up visits. Among 666 infants reported sick, 94.3% were taken to a healthcare facility, with only 41.9% (range across sites: 4.9–77.3%) to the study site. Conclusion: Although high retention was observed from enrolment through 90 days after delivery, post-partum surveillance should be broadened beyond the study sites and additional follow-up visits should be planned within the neonatal period. The factors influencing maternal/infant access to healthcare facilities and the issues identified in this study should be taken into consideration in planning future clinical studies on maternal immunisation in low- and middle-income countries.
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    Prevalence of Group B Streptococcus colonization and serotype distribution among pregnant women in South Asian and African countries
    (University of the Witwatersrand, Johannesburg, 2024) Kwatra, Gaurav; Madhi, Shabir A.
    Background: Recto-vaginal Group B Streptococcus (GBS) colonization in pregnant women at the time of labour is the major risk-factor for developing invasive GBS disease within 7 days of age (early onset disease; EOD). We investigated prevalence of GBS recto-vaginal colonization at the time of labour among pregnant women and vertical transmission to their newborns across six African and two south-Asian countries. Methods: This multi-country prospective, observational cross-sectional study was undertaken in six African [(Ethiopia (Adama city), Kenya (Kilifi), Mozambique (Manhica), Nigeria (Gwagwalada), Mali (Bamako) and South Africa (Johannesburg) and two Southeast Asian countries (Bangladesh (Mirzapur) and India (Vellore)]. Inclusion criteria included pregnant women 18 to 45 years of age, delivery at ≥37 weeks gestation and documented to be HIV-uninfected prior to study-enrolment. Lower vaginal swabs, rectal swabs and urine were collected from the mothers and separate skin surface swabs of the umbilicus, outer ear and axillary fold; and rectal and throat swabs were obtained from the newborn for GBS culture. Standardized sampling and culture using direct plating and selective broth media for detection of GBS colonization in the mother-newborn dyads was undertaken across the sites. Serotyping of GBS isolates was done in South Africa. Results: Overall, 6,922 pregnant women were enrolled from January 10th , 2016 to December 11th , 2018. Of 6922 women who were enrolled, 6514 (94.1%; 759 to 892 per site) were included in the analysis. Overall, the prevalence of maternal GBS colonization was 24.1% (95%CI 23.1- 25.2; 1572/6514) being highest in Mali (41.1%, 95%CI: 37.7-44.6; 314/764) and lowest in Ethiopia (11.6%, 95%CI:9.5-14.1; 88/759). The overall rate of vertical transmission of GBS was 72.3% (95%CI 70.0-74.4; 1132/1566); being highest in Mozambique (79.2%, 95%CI 73.3-84.2); 168/212) and lowest in Bangladesh (55.8%, 95%CI 47.5-63.8; 77/138). The five most common GBS colonizing serotypes were Ia (37.3%; 586/1572), V (28.5%; 448/1572), III (25.1%; 394/1572), II (9.2%; 144/1572) and Ib (6.5%; 102/1572). There was geographic variability in serotype proportion distribution. Serotype VII was the third most common serotype in India (8.5%, n=15/176) and serotype VI was mainly identified in Bangladesh (5.8%) and India (5.7%). Conclusion: Our study reported high prevalence of GBS colonization in most settings, with some geographic variability even within African countries. Our findings suggests that there is likely to be a significant burden of EOD across the study sites. Post-licensure vaccine effectiveness studies should also focus on maternal GBS serotype distribution as non-vaccine serotype replacement could occur due to vaccine immune pressure
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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.