Associations Between Histo-blood Group Antigen Status in Mother-Infant Dyads and Infant Oral Rotavirus Vaccine Immunogenicity in Rural Zimbabwe

BACKGROUND: Histo-blood group antigen (HBGA) phenotypes may contribute to poor oral rotavirus vaccine (RVV) immunogenicity, since rotavirus binds intestinal epithelial HBGA glycans, while maternal HBGA status shapes breastmilk composition, which influences the composition of the infant microbiome. We investigated associations between maternal/infant HBGA phenotypes and RVV immunogenicity in rural Zimbabwe. METHODS: We undertook salivary FUT2/FUT3 phenotyping in mother-infant pairs. Serum anti-rotavirus immunoglobulin A was measured by enzyme-linked immunosorbent assay. We explored adjusted associations between FUT2/FUT3 status and RVV seroconversion (primary outcome, n = 322) and seropositivity and geometric mean titer (secondary outcomes, n = 776). RESULTS: Infants of FUT2- or FUT3-positive women were less likely to seroconvert post-RVV than infants of FUT2- or FUT3-negative women (FUT2 positive [20.1%] vs FUT2 negative [27.5%]: adjusted relative risk [aRR], 0.47; 95% CI, .26-.82; P = .008; FUT3 positive [18.1%] vs FUT3 negative [30.0%]: aRR, 0.45; 95% CI, .25-.78; P = .005). When compared with FUT2-positive infants with FUT2-positive mothers, FUT2-positive infants with FUT2-negative mothers were twice as likely to seroconvert (36.8% vs 21.9%; aRR, 2.12; 95% CI, 1.23-3.63; P = .006). When compared with FUT3-positive infants with FUT3-positive mothers, FUT3-positive infants with FUT3-negative mothers were 3 times as likely to seroconvert (48.3% vs 18.2%; aRR, 2.99; 95% CI, 1.82-4.90; P < .001). CONCLUSIONS: Maternal and infant FUT2 and FUT3 status influences infant RVV immunogenicity.