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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

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



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.


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.


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).


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.


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