Histo-Blood Group Antigen Phenotype Determines Susceptibility to Genotype-Specific Rotavirus Infections and Impacts Measures of Rotavirus Vaccine Efficacy

J Infect Dis. 2018 Apr 11;217(9):1399-1407. doi: 10.1093/infdis/jiy054.

Abstract

Background: Lewis and secretor histo-blood group antigens (HBGAs) have been associated with decreased susceptibility to P[8] genotype rotavirus (RV) infections. Efficacy of vaccines containing attenuated P[8] strains is decreased in low-income countries. Host phenotype might impact vaccine efficacy (VE) by altering susceptibility to vaccination or RV diarrhea (RVD). We performed a substudy in a monovalent RV vaccine (RV1) efficacy trial in Bangladesh to determine the impact of Lewis and secretor status on risk of RVD and VE.

Methods: In infants randomized to receive RV1 or no RV1 at 10 and 17 weeks with 1 year of complete active diarrheal surveillance, we performed Lewis and secretor phenotyping and genotyped the infecting strain of each episode of RVD.

Results: A vaccine containing P[8] RV protected secretors and nonsecretors similarly. However, unvaccinated nonsecretors had a reduced risk of RVD (relative risk, 0.53 [95% confidence interval, .36-.79]) mediated by complete protection from P[4] but not P[8] RVs. This effect reduced VE in nonsecretors to 31.7%, compared to 56.2% among secretors, and decreased VE for the overall cohort.

Conclusions: Host HBGA status may impact VE estimates by altering susceptibility to RV in unvaccinated children; future trials should therefore account for HBGA status.

Clinical trials registration: NCT01375647.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bangladesh
  • Blood Group Antigens / genetics*
  • Diarrhea / prevention & control
  • Diarrhea / virology
  • Genotype*
  • Humans
  • Infant
  • Rotavirus / classification*
  • Rotavirus Infections / prevention & control*
  • Rotavirus Infections / virology
  • Rotavirus Vaccines / immunology*
  • Vaccines, Attenuated / immunology

Substances

  • Blood Group Antigens
  • Rotavirus Vaccines
  • Vaccines, Attenuated

Associated data

  • ClinicalTrials.gov/NCT01375647