Genetic Susceptibility to Rotavirus Gastroenteritis and Vaccine Effectiveness in Taiwanese Children

Abstract

The genetic susceptibility to and vaccine effectiveness against rotavirus gastroenteritis were different in distinct ethnic groups. The case-control study was aimed to evaluate the effectiveness of rotavirus vaccines and associations between the histo-blood group antigens and susceptibility to rotavirus infections in a Taiwanese population. Cases were children <18 years old who were hospitalized because of laboratory-confirmed rotavirus infection. Controls were healthy children matched to cases by age and gender. The secretor status and Lewis antigen and ABO types were determined by molecular methods. A total of 68 cases and 133 controls were included. Rotavirus immunization was recorded in 8 (12%) cases and 77 (58%) controls, indicating a vaccine effectiveness of 90.3% (95% confidence interval [CI], 78.1% − 95.7%). The secretor and Lewis-positive genotypes were independently associated with increased risk of rotavirus infections (matched odds ratio [mOR] 28.5, 95% CI 2.94–277, P = 0.003 and mOR 16.8, 95% CI 1.08–2601, P = 0.04, respectively). The distribution of ABO blood types did not differ significantly between cases and controls (P = 0.47). In conclusion, Taiwanese children with the secretor genotype and Lewis-positive genotype were at increased risk of moderate-to-severe rotavirus infections. The illness can be effectively prevented by immunization in this population.

Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection

“…Thus, the results of the study suggested that the recognition of α(1,2)-fucosylated antigens by the VP8* protein could be essential for symptomatic infection by P[8] strains. Other epidemiological studies confirmed and completed these results 20 , 25 – 28 . Recent studies further underscored the importance of the secretor status by showing elevated RV specific antibodies in the serum and saliva of secretor individuals 20 , 29 , 30 .…”

Maternal Human Milk Oligosaccharide Profile Modulates the Impact of an Intervention with Iron and Galacto-Oligosaccharides in Kenyan Infants

“…Our findings show that maternal secretor status does not have a major impact on the gut microbiota of the mothers. Previous studies have linked maternal secretor status to a higher risk for viral infections, including norovirus [7,8,66], rotavirus [9,10,11,58,67,68] and respiratory viruses [12] in women. In contrast, maternal non-secretor status has been linked with symptomatic ETEC infection in women [13].…”

“…Frequency of the secretor phenotype is estimated at ~80% worldwide but varies between geographical regions [3,6]. The secretor phenotype predicts a higher risk for viral infections (e.g., norovirus [7,8], rotavirus [9,10,11] and respiratory viruses [12]), while the non-secretor phenotype predicts risk for enterotoxigenic Escherichia coli (ETEC) infection [13]. Two recent large cohort studies in the United Kingdom and Canada found no association between maternal secretor status and the overall maternal gut microbiota composition [14,15].…”

Fondness for sugars of enteric viruses confronts them with human glycans genetic diversity

“…linkage. This is catalyzed by the α1,3 galactosyltransferase of the GT6 or ABO family Kambhapati et al 2015;Nordgren et al 2014;Yang et al 2017). These countries present a good match between genetic susceptibility to the disease, circulating strains and vaccine strains, explaining the high vaccine effectiveness.…”

“…Thus, the VP8* attachment protein domain from strains of the P[8] and P[4] genotypes specifically binds to the Lewis b antigen (Barbé et al 2018;Huang et al 2012;Liu et al 2012b;Sun et al 2016a). Epidemiological studies reported a strong association between RVA gastroenteritis and the secretor phenotype, consistent with the requirement of a functional FUT2 allele for synthesis of the Lewis b antigen in the small intestine (Imbert-Marcille et al 2013;Kambhapati et al 2015;Nordgren et al 2014;Sun et al 2016b;Van Trang et al 2014;Yang et al 2017). Studies performed in Burkina Faso and China additionally reported a much lower risk among children presenting a Lewis negative phenotype, also consistent with the requirement of the FUT3 enzyme in the synthesis of the Lewis b structure (Nordgren et al 2014;Yang et al 2017) and in accordance with a recent structural study showing that both the a1,2 and a1,4-linked fucose residues are involved in the P[8] VP8* binding site (Xu et al 2019).…”