Citation: Chauwa, A.; Bosomprah, S.; Laban, N.M.; Phiri, B.; Chibuye, M.; Chilyabanyama, O.N.; Munsaka, S.; Simuyandi, M.; Mwape, I.; Mubanga, C.; et al. Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix TM ) Immunogenicity among Infants in Zambia. Vaccines 2023, 11, 1303. https://doi.org/10.3390/ vaccines11081303 Academic Editor: Tohru Suzuki Received: 24 May 2023 Revised: 12 July 2023 Accepted: 24 July 2023 Published: 31 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Article Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix TM ) Immunogenicity among Infants in Zambia Adriace Chauwa 1,2, *, Samuel Bosomprah 1,3 , Natasha Makabilo Laban 1,4 , Bernard Phiri 1 , Mwelwa Chibuye 1,5 , Obvious Nchimunya Chilyabanyama 1 , Sody Munsaka 2 , Michelo Simuyandi 1 , Innocent Mwape 1 , Cynthia Mubanga 1 , Masuzyo Chirwa Chobe 1 , Caroline Chisenga 1 and Roma Chilengi 1 1 Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia; samuel.bosomprah@cidrz.org (S.B.); natasha.laban@cidrz.org (N.M.L.); bernard.phiri@cidrz.org (B.P.); mwelwa.chibuye@cidrz.org (M.C.); chilyabanyama@gmail.com (O.N.C.); michelo.simuyandi@cidrz.org (M.S.); innocent.mwape@cidrz.org (I.M.); cynthia.mubanga@cidrz.org (C.M.); masuzyo.chirwa@cidrz.org (M.C.C.); caroline.chisenga@cidrz.org (C.C.); roma.chilengi@cidrz.org (R.C.) 2 Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia; s.munsaka@unza.zm 3 Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana 4 Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 5 Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1012 WP Amsterdam, The Netherlands * Correspondence: adriace.chauwa@cidrz.org Abstract: Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low- income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX ® ) vaccine- induced responses in Zambia. We studied 135 mother–infant pairs under a rotavirus vaccine clinical trial, with infants aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months, though no statistically significant difference was observed between the study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGAs were associated with RV vaccine immunogenicity at 12 months as opposed to in early infant life. Further investigation into the low efficacy of ROTARIX ® and appropriate intervention is key to unlocking the full vaccine benefits for U5 children. Keywords: rotavirus; vaccines; histo-blood groups; immunogenicity; Zambia 1. Introduction Rotavirus is known to be the leading cause of moderate-to-severe acute gastroenteritis in infants and children under the age of 5 years (U5) globally, but more so in low- and middle-income countries (LMICs) [1]. In 2017, the Global Burden of Disease (GBD) study estimated total diarrhoea deaths in the U5 population attributable to RV to be between 120,000 and 215,000 [2]. Vaccines against rotavirus, such as ROTARIX ® (GlaxoSmithKline Biologicals, Rixensart, Germany), a G1(P8) strain-derived live-attenuated oral vaccine, have been rolled out in a national expanded program on immunisation (EPI) schedules in many Vaccines 2023, 11, 1303. https://doi.org/10.3390/vaccines11081303 https://www.mdpi.com/journal/vaccines