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Clin Infect Dis. 2018 Dec 18. doi: 10.1093/cid/ciy1067. [Epub ahead of print]

Non-secretor histo-blood group antigen phenotype is associated with reduced risk of clinical rotavirus vaccine failure in Malawian infants.

Author information

1
Centre for Global Vaccine Research, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
2
Malawi Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.
3
Medical Laboratory Sciences Department, College of Medicine, University of Malawi, Blantyre, Malawi.
4
Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi.
5
International Vaccine Access Center, Dept. International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
6
Division of Infection and Immunity, University College London, London, UK.
7
National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at University of Liverpool.

Abstract

Background:

Histo-blood-group-antigen (HBGA) Lewis/secretor phenotypes are associated with susceptibility to genotype-specific rotavirus gastroenteritis (RVGE). We tested the hypothesis that non-secretor/Lewis negative phenotype leads to reduced vaccine virus replication, IgA response and clinical protection following vaccination with G1P[8] rotavirus vaccine (RV1) in Malawian infants.

Methods:

Infants receiving RV1 at age six and ten weeks were recruited to a cohort study. HBGA phenotype was determined by salivary ELISA. RV1 vaccine virus shedding was detected by qRT-PCR in stool collected on alternate days for ten days post-immunization. Plasma rotavirus (RV)-specific IgA was determined by ELISA pre-immunisation and following the second dose. In a case-control study, distribution of HBGA phenotype was compared between RV1-vaccinated infants hospitalized 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 faecal shedding nor seroconversion differed by secretor or Lewis phenotype. In 238 matched case-control infants, non-secretor phenotype was significantly less common in infants with clinical vaccine failure (OR 0.39, 95%CI 0.20-0.75). The prevalence of non-secretor 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:

Non-secretor phenotype was associated with reduced risk of rotavirus vaccine failure. There was little evidence of a significant association between HBGA phenotype and vaccine take. These data refute the hypothesis that high prevalence of non-secretor/Lewis negative phenotypes contributes to lower rotavirus vaccine effectiveness in Malawi.

PMID:
30561537
DOI:
10.1093/cid/ciy1067

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