Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014–2018

Abstract

Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1 st /2 nd RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a−b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility. After implementation of the rotavirus vaccines, Rotarix ® (RV1, GlaxoSmithKline Biologicals, Rixensart, Belgium) and RotaTeq ® (RV5, Merck Inc., USA), in over 100 countries worldwide 1 , the burden of severe group A rotaviruses (RVA) diarrhea has decreased substantially, with reductions in hospitalizations and deaths in many countries, including Brazil 2-6. However, RVA still are one of major causes of severe viral diarrhea in infants and young children <5-years-old worldwide 6,7. Due to the zoonotic potential, variability of the RVA strains and host genetic factors, the surveillance of circulating RVA strains is necessary for evaluating and monitoring the effectiveness of the implemented immunization programs, mainly in low-income countries 8. Currently, 36 G-and 51 P-genotypes have been described 9 and globally, six G/P combinations are the most prevalent in humans: G1P[8], G2P[4], G3P[8], G9P[8], G4P[8] and G12P[8] 10 .

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

“…For example, Rotarix was different from other P [8] strains of the same lineage I, showing a lack of interaction with the α1,2 fucosylated H type 1 antigen present in secretors [6]. These results suggest that different P [8] strains, including the vaccine Rotarix, may differ in terms of secretor mediated susceptibility, which has also been suggested in epidemiological studies [7,8]. Moreover, a recent study suggested that the strains of the emerging lineage P[8]-4 more readily infect non-secretors compared to other P [8] strains [8], further demonstrating that there can be a difference in secretor-specificity between lineages of the same P-genotype.…”

“…Infection with the P [6]-genotype is strongly associated with Lewis negativity, independent of secretor status. However, variations in secretor-specificity has been observed between studies, as well as between and within lineages of P [8]-genotypes, including the Rotarix vaccine [2,7,8].…”

Epidemiology of enteric virus infections in children living in the Amazon region

“…The ABO (H), secretor (FUT2) and Lewis (FUT3) system genes control the expression of part of the histo-blood group antigens (HBGA) acting as genetic host susceptibility factors. HBGAs mediate norovirus and RVA infections and might impact RV1 vaccine efficacy (Cantelli et al, 2020;Sharma et al, 2020;Nordgren and Svensson, 2019;Heggelund et al, 2017;Desselberger, 2017).…”

FUT2, Secretor Status and FUT3 Polymorphisms of Children with Acute Diarrhea Infected with Rotavirus and Norovirus in Brazil

“…Indeed, higher vaccine take has been observed in children with the secretor phenotype, compared to non-secretors [ 43 , 52 , 53 ]. Interestingly, in a recent study assessing the association of rotavirus shedding and the HBGA profile in a birth community-cohort in Rio de Janeiro, Brazil, a mutation in the 167 position of the VP8* P[8] gene was detected in many samples characterized as Rotarix ® strain (RV1) [ 54 ]. Moreover, Le a+b+ secretor children were significantly more likely to shed this mutant strain compared to non-secretors.…”

“…Moreover, Le a+b+ secretor children were significantly more likely to shed this mutant strain compared to non-secretors. Based on these results, it was suggested that the RV1-vaccine replication triggered by this mutational event led to a more robust immune response in these children [ 54 ].…”