EFFECT OF SECRETOR/LEWIS PHENOTYPE ON ROTAVIRUS-SPECIFIC IGA RESPONSE, VACCINE TAKE AND CLINICAL PROTECTION FOLLOWING MONOVALENT ROTAVIRUS VACCINATION IN MALAWIAN INFANTS
L Pollock1,2, A Bennett1,2, K Jere1,2, Q Dube3, N Bar-Zeev1,2, R Heyderman4, N Cunliffe1, M Iturriza Gomara1
Affiliation details:
1.Institute of Infection and Global Health, University of Liverpool, UK
2.Vaccines Group, Malawi Liverpool Wellcome Trust, Malawi
3.Department of Paediatrics, College of Medicine, Malawi
4.Division of Infection and Immunity, University College London, UK
Background
Histo-blood-group-antigen(HBGA) Lewis/secretor phenotypes are associated with genotype-specific susceptibility to rotavirus infection. We tested the hypothesis that intrinsic resistance of Lewis negative/non-secretors to G1P[8] infection results in reduced IgA response, vaccine virus replication and clinical protection following monovalent P[8]-based rotavirus vaccine in Malawian infants.
Methods
Infants received 2 doses of monovalent G1P[8] rotavirus vaccine (RV1) at 6 and 10 weeks of age.  Stool was collected on alternate days for 10 days post-vaccine and vaccine virus shedding determined by qRT-PCR. Post-vaccine serum rotavirus-specific IgA was determined by ELISA, with seroconversion defined as fourfold rise in concentration. HBGA phenotype was determined by salivary ELISA. Clinical protection was determined by comparing vaccinated infants <12 months with rotavirus gastroenteritis (RVGE) to age-matched, vaccinated controls. Rotavirus genotype was determined by RT-PCR.
Results
In 202 cohort infants, Leb+ secretor phenotype was associated with increased likelihood of vaccine virus replication (RR 1.5 (95%CI 1.1-2.1) p=0.009), but there was no association between any HBGA phenotype and seroconversion. Genotype was available for 113/120 RVGE cases. G1P[8] RVGE (OR 10.6 (95%CI 3.1-35.7) p<0.001) and P[4] infections (OR 4.9 (95%CI 1.9-10.4) p=0.001) were positively associated with Leb+ secretor phenotype. Comparing 119 RVGE cases to 212 controls, non-secretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure (OR 0.40 (95%CI 0.21-0.78), p=0.007).
Conclusions
We found evidence that Leb-/non-secretor infants have reduced vaccine virus replication, but adequate IgA response to rotavirus vaccination. Contrary to our hypothesis, non-secretor infants were at decreased risk of clinical vaccine failure. Any reduced vaccine response in non-secretors is offset by protection against common P[8] and P[4] strains. HBGA phenotype is unlikely to contribute to reduced rotavirus vaccine effectiveness in Malawi or other low-income countries with similar rotavirus strain diversity.

EFFECT OF SECRETOR/LEWIS PHENOTYPE ON ROTAVIRUS-SPECIFIC IGA RESPONSE, VACCINE VIRUS REPLICATION AND CLINICAL PROTECTION FOLLOWING MONOVALENT ROTAVIRUS VACCINATION IN MALAWIAN INFANTS