Nonsecretor Histo–blood Group Antigen Phenotype Is Associated With Reduced Risk of Clinical Rotavirus Vaccine Failure in Malawian Infants

Author:

Pollock Louisa12ORCID,Bennett Aisleen12,Jere Khuzwayo C123,Dube Queen4,Mandolo Jonathan2,Bar-Zeev Naor25,Heyderman Robert S26,Cunliffe Nigel A1,Iturriza-Gomara Miren17

Affiliation:

1. Centre for Global Vaccine Research, Institute of Infection and Global Health, University of Liverpool, United Kingdom

2. Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi, Blantyre

3. Medical Laboratory Sciences Department, University of Malawi, Blantyre

4. Department of Paediatrics, College of Medicine, University of Malawi, Blantyre

5. International Vaccine Access Center, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

6. Division of Infection and Immunity, University College London, United Kingdom

7. National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, United Kingdom

Abstract

Abstract Background Histo–blood group antigen (HBGA) Lewis/secretor phenotypes predict genotype-specific susceptibility to rotavirus gastroenteritis (RVGE). We tested the hypothesis that nonsecretor/Lewis-negative phenotype leads to reduced vaccine take and lower clinical protection following vaccination with G1P[8] rotavirus vaccine (RV1) in Malawian infants Methods A cohort study recruited infants receiving RV1 at age 6 and 10 weeks. HBGA phenotype was determined by salivary enzyme-linked immunosorbent assay (ELISA). RV1 vaccine virus shedding was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in stool collected on alternate days for 10 days post-immunization. Plasma rotavirus–specific immunoglobulin A was determined by ELISA pre- and post-immunization. In a case-control study, HBGA phenotype distribution was compared between RV1-vaccinated infants with RVGE and 1:1 age-matched community controls. Rotavirus genotype was determined by RT-PCR. Results In 202 cohort participants, neither overall vaccine virus fecal shedding nor seroconversion differed by HBGA phenotype. In 238 case-control infants, nonsecretor phenotype was less common in infants with clinical vaccine failure (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.20–0.75). Nonsecretor phenotype was less common in infants with P[8] RVGE (OR, 0.12; 95% CI, 0.03–0.50) and P[4] RVGE (OR, 0.17; 95% CI, 0.04–0.75). Lewis-negative phenotype was more common in infants with P[6] RVGE (OR, 3.2; 95% CI, 1.4–7.2). Conclusions Nonsecretor phenotype was associated with reduced risk of rotavirus vaccine failure. There was no significant association between HBGA phenotype and vaccine take. These data refute the hypothesis that high prevalence of nonsecretor/Lewis-negative phenotypes contributes to lower rotavirus vaccine effectiveness in Malawi.

Funder

Wellcome Trust Clinical

Wellcome Trust Programme

MLW Programme Core Grant Strategic Award

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Reference36 articles.

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5. Histo-blood group antigen phenotype determines susceptibility to genotype-specific rotavirus infections and impacts measures of rotavirus vaccine efficacy;Lee;J Infect Dis,2018

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