Browsing by Author "Mwila-Kazimbaya K"

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Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach.
(2023) Mwila-Kazimbaya K; Bosomprah S; Chilyabanyama ON; Chisenga CC; Chibuye M; Laban NM; Simuyandi M; Huffer B; Iturriza-Gomara M; Choy RKM; Chilengi R
BACKGROUND: Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach. METHODS: Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers. RESULTS: Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only. CONCLUSION: MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.
Immunogenicity and safety of two monovalent rotavirus vaccines, ROTAVAC® and ROTAVAC 5D® in Zambian infants.
(2021-Jun-16) Chilengi R; Mwila-Kazimbaya K; Chirwa M; Sukwa N; Chipeta C; Velu RM; Katanekwa N; Babji S; Kang G; McNeal MM; Meyer N; Gompana G; Hazra S; Tang Y; Flores J; Bhat N; Rathi N
BACKGROUND AND AIMS: ROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia. METHODS: We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose. RESULTS: The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period. CONCLUSIONS: Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.