Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh

Abstract

Secretor status controls mucosal histo–blood group antigen expression and is associated with susceptibility to rotavirus (RV) diarrhea, with nonsecretors less susceptible to symptomatic infection. The role of breast milk secretor status on oral live-attenuated RV vaccine response in breastfed infants has not been explored. In a monovalent G1P[8] RV vaccine (Rotarix) trial in Bangladesh, RV-specific plasma immunoglobulin A antibody seroconversion rates were higher among infants of maternal nonsecretors (39%) than infants of maternal secretors (23%; P = .001). Maternal status remained a significant predictor when correcting for infant status (P = .002). Maternal secretor status should be considered when interpreting oral RV vaccine responses in low- and middle-income settings. Clinical Trials Registration. NCT01375647.

Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take—An Overview

“…However, few studies have addressed this question directly. One such study from Bangladesh observed that breastfed children whose mothers were secretors had less IgA seroconversion rates after vaccination, compared to children whose mothers were non-secretors [44], with the infant serum rotavirus IgG titers being higher in the children of secretor mothers. More studies are thus needed to assess to which degree maternal secretor status and, thus, maternal antibody levels affect the rotavirus vaccine response in infants.…”

“…Apart from rotavirus IgA titers in breastmilk, non-antibody components of breastmilk may also directly affect vaccine take in a secretor-dependent manner, both by facilitating or restricting vaccine strain infection, depending on type of rotavirus vaccine or administration schedule [44,73,74]. Fucosylated glycans in milk of secretor mothers have been reported to provide protection to diarrhea in breastfed infants [75].…”

Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines

“…Studies from Ghana and Pakistan have reported decreased rates of RV-IgA seroconversion among infant secretors, 111,112 while no such differences were found in studies from Bangladesh and Malawi. 113,114 Additional findings from the Bangladesh study offer a potential explanation. In this study, infants born to maternal non-secretors had significantly increased risk of seroconversion compared to infants born to maternal secretors, and the greatest affect was observed in infants who were themselves secretor-positive but born to non-secretor mothers, with 73% seroconversion in secretor-positive infants born to genotypeconfirmed non-secretor mothers, compared to 23% in those born to genotype-confirmed secretor mothers.…”

“…In this study, infants born to maternal non-secretors had significantly increased risk of seroconversion compared to infants born to maternal secretors, and the greatest affect was observed in infants who were themselves secretor-positive but born to non-secretor mothers, with 73% seroconversion in secretor-positive infants born to genotype-confirmed non-secretor mothers, compared to 23% in those born to genotype-confirmed secretor mothers. 114 A proposed mechanism for this effect is that FUT2 -dependent HMOs present in breast milk may act as decoy receptors for vaccine-strain virus; this could explain why vaccinated infants without interference from breast milk ligands but who expressed 2-fucosylated HBGAs on the gut surface (i.e. secretor infants born to maternal non-secretors) had the highest rates of vaccine seroconversion.…”

“…secretor infants born to maternal non-secretors) had the highest rates of vaccine seroconversion. 114 Inability to account for maternal secretor status is a possible explanation for the discordant results reported for infant secretor status across studies, but this requires further investigation.…”