Antibody and T-cell responses in rotavirus vaccinated Zambian infants: impact of human cytomegalovirus infection

Oral rotavirus vaccines (ORV) demonstrate lower seroconversion rates in low-income compared to high-income settings, a phenomenon that is not fully understood. There is also limited knowledge on the T-cell immune responses in vaccinated infants creating a gap in understanding rotavirus immunology. I used plasma and peripheral blood mononuclear cells collected from infants under a rotavirus vaccine trial in Zambia to measure the rotavirus specific immunoglobulin IgA (RV-IgA) antibody responses comparing two and three doses of an ORV (Rotarix) and the T cell responses associated with vaccination. I also investigated the influence of human cytomegalovirus immunoglobulin M (HCMV-IgM) seropositivity on vaccine immunogenicity. To contribute to coronavirus research, post the COVID-19 pandemic, I explored antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common cold coronaviruses among this mother-infant rotavirus trial study cohort. A low seroconversion rate of 27.8% was observed one month after two dose ORV administration and there was no significant boosting of RV-IgA three months after a third ORV dose administered at 9 months (p=0.223). HCMV-IgM seropositivity did not affect RV-IgA responses among overall infants but significantly reduced RV-IgA responses by 63% in HIVexposed-uninfected infants (p=0.008). Limited and very low frequency rotavirus VP6-specific T-cell responses were detected in vaccinated infants but enriched rotavirus VP6-specific CD4+ T-cell responses were observed among vaccine seroconverters. Overall, the thesis provided evidence that a booster ORV dose at 9 months did not improve vaccine immunogenicity by 12 months suggesting alternate rotavirus vaccine strategies or formulations may be necessary to improve vaccine immunogenicity in Zambia, and that HCMV-IgM seropositive HIV-exposed-uninfected infants were sub-populations vulnerable to reduced rotavirus immunity. The limited rotavirus-specific T-cell responses suggested that infants mount short-lived memory T-cell responses to ORV but also showed evidence of VP6-targeted CD4 T-cell dependent antibody response to rotavirus vaccination.