Histo–blood group antigen phenotype determines susceptibility to genotype-specific rotavirus infections and impacts measures of rotavirus vaccine efficacy
B Lee, DM Dickson, AC deCamp… - The Journal of …, 2018 - academic.oup.com
The Journal of infectious diseases, 2018•academic.oup.com
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 …
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 …
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.
Oxford University Press