Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype–Dependent Manner

Abstract

As VP4 of genotype P[8] is a component of current RV vaccines, our finding that Lewis-negative children are resistant to P[8] strains provides a plausible explanation for the reduced vaccine efficacy in populations with a high percentage of Lewis-negative individuals, such as in Africa. Furthermore, our findings provide a plausible explanation as to why P[6] RV strains are more common in Africa.

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

“…Similarly, the Lewis-negative phenotype is significantly more common in parts of Africa (reaching >30% in some populations) than in Caucasians (4-6%) [83]. Thus, an impaired replicative capacity of P[8] strains combined with the high prevalence of P[6] genotypes in Lewis-negative individuals, as reported in Burkina Faso [78], would be consistent with observed discrepancies in rotavirus vaccine efficacy.…”

“…Similarly, the Lewis-negative phenotype is significantly more common in parts of Africa (reaching >30% in some populations) than in Caucasians (4-6%) [83]. Thus, an impaired replicative capacity of P[8] strains combined with the high prevalence of P[6] genotypes in Lewis-negative individuals, as reported in Burkina Faso [78], would be consistent with observed discrepancies in rotavirus vaccine efficacy.A key challenge for the coming years will be to determine the extent to which host genetic determinants of rotavirus diarrhea susceptibility apply to attenuated vaccine strains. Notably, during a recent study in Pakistan, Rotarix immunogenicity was associated with secretor status and ABO blood group -seroconversion was seen in 19% of nonsecretors, 30% of secretors with non-O blood groups and 51% of secretors with blood group O [84].…”

“…A recent systematic review based on studies in France, Vietnam, the USA and Burkina Faso documented a 27-fold increase in susceptibility to P[8] rotavirus in secretors versus nonsecretors, but showed no association between secretor status and susceptibility to P[4] or P[6] genotypes [75]. In Burkina Faso, no Lewis-negative secretors (expressing H type 1 antigen) were infected with P[8] strains, despite making up 25% of the study population [78], suggesting that the infectivity of P[8] strains may be dependent on both secretor and Lewis status. However, population-specific differences may exist; for example, P[8] infections were detected in both secretors and nonsecretors during a study in Tunisia [79].…”

Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades

“…Thirty-four serum samples collected from children with type 1 diabetes (aged 9.7 Ϯ 3.2 years at the time of the 1st sample collection) were also included: 12 paired sera collected at 2 time points (the second serum samples 5 years later) and 10 unpaired old serum samples collected between 1979 and 1981 were included in the study. Additionally, sera from 40 IgA-deficient individuals (34 secretors and 6 nonsecretors) collected between 2009 and 2010 were included (30). The average age of these individuals was 52.3 Ϯ 19.4 years.…”

“…Although the deficiency is common, there is limited information about how these individuals respond to NoV infection and whether they develop serum blocking IgG antibodies following a natural infection. To address this question, we investigated sera from 40 previously confirmed secretor and nonsecretor IgA-deficient individuals (30). All six IgA-deficient nonsecretor individuals lacked blocking antibodies (BT 50 Ͻ 40) (data not shown).…”