Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants

Filemón Bucardo,Fredman González,Lennart Svensson,Sumit Sharma,Johan Nordgren,Yaoska Reyes,Ylva Rönnelid

doi:10.1038/s41598-019-47166-9

Abstract

ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (≤3, 4–7 and ≥8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at ≥4 days post vaccination (DPV). At ≥4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (>13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.

Highlights

Rotaviruses typically infect the gastrointestinal tract and are shed in very large amounts (>108 genomes/gram of feces) for several days in feces of symptomatic and asymptomatic infants following natural infections1–3
In the Rotarix cohort, shedding rates was highest for infants of blood group A (18%, relative risk (RR) = 1.7 [95% confidence intervals (CI): 0.4–7.7]), whereas in the RotaTeq cohort, rotavirus shedding was lower (7%, RR = 0.3, [95% CI: 0.04–2.3) for infants of blood group A as compared to blood group O (30%) and B (22%) (Table 1)
We have investigated if histo-blood group antigens (HBGA) affect viral replication of Rotarix and RotaTeq vaccine strains in infants by determining rotavirus shedding at different time points after first dose of vaccination

Summary

Introduction

Rotaviruses typically infect the gastrointestinal tract and are shed in very large amounts (>108 genomes/gram of feces) for several days in feces of symptomatic and asymptomatic infants following natural infections. In a safety and immunogenicity trial of live, attenuated human rotavirus vaccine 89–12 (precursor to the Rotarix vaccine, genotype G1P[8]), rotavirus shedding after one dose was nil in adults, 15% in rotavirus IgA seropositive infants (2 to 12 year) and 70% in rotavirus IgA seronegative infants (6 to 26 weeks). The comprehension of how multivalent rotavirus vaccine prevent disease is more complex in terms of host susceptibility, viral replication and development of immune response. These vaccines contain multiple reassortant viruses derived from human and animal strains which may have limited permissiveness in the human host. It is of interest to investigate whether replication/shedding of the different strains and P-genotypes in the RotaTeq vaccine are associated with HBGA phenotypes

Methods

Results

Conclusion