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

Abstract

Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed.

Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (RotarixTM) Immunogenicity among Infants in Zambia

“…Of note, our study showed a higher rate of seroconversion among secretors compared to non-secretors ( Table 2 ), as previously documented [ 26 , 35 , 36 ]. This is not surprising as the literature has shown that secretors express HBGAs on their gut-mucosal epithelia, which serve as receptors for 2 attachment—in this case, a vaccine-derived live-attenuated virus—which could explain the higher immune responses seen in secretors compared to non-secretors.…”

Infant Non-Secretor Histoblood Group Antigen Phenotype Reduces Susceptibility to Both Symptomatic and Asymptomatic Rotavirus Infection

“…Additional clues may be provided by examination of patterns of post-vaccination fecal vaccine shedding [ 15 ]. In studies conducted in Brazil, Nicaragua and Malawi, significantly lower frequencies of post-vaccination Rotarix shedding was observed in non-secretors [ 26 , 27 , 28 ].…”

“…Because of the association of secretor status with susceptibility to rotaviruses, likely in a P-genotype-dependent manner, numerous additional studies have examined whether this could influence the vaccine take of various LORVs, as reviewed elsewhere [ 15 ]. However, there are few data on whether secretor status also influences the risk of asymptomatic infection with wild-type (i.e., unattenuated) rotaviruses in young children.…”

Maternal Breast Milk Secretor Phenotype Does Not Affect Infant Susceptibility to Rotavirus Diarrhea

“…In a larger sample size of week 6 RV-IgG antibody measurements (ie, transplacentally acquired maternal antibodies), RV-IgG in infants of maternal secretors was significantly higher than in infants of nonsecretors, consistent with findings in adults [ 10 ]. Due to limitations in available sample size, we failed to detect this difference previously when assessing only vaccinated children with complete data [ 5 ], and it is indeed highly plausible that differences in vaccine immunogenicity based on maternal status may be driven primarily by this effect on maternal antibody levels [ 11 ]. Despite this, neither maternal status nor maternal antibody concentration was significantly associated with risk of RV diarrhea in either vaccinated or unvaccinated children when controlling for other pertinent variables, although results should be interpreted with caution, again due to small sample sizes.…”