Investigating barriers to the protective efficacy provided by rotavirus vaccines in African infants
Authors: Julie E. Bines
Journal: PLoS Medicine (2021)

The introduction of rotavirus vaccines into the national immunization programs globally has made a major impact on diarrhea-related hospitalizations and deaths.By 2020, 107 countries had introduced rotavirus vaccines, either nationally or regionally, including 52 countries in Africa and Asia eligible for funding through the Global Alliance for Vaccines and Immunization (Gavi) [1].This represents a major step toward reducing under 5-year child mortality, the impact of rotavirus disease on child health, and the economic burden on families and the healthcare system.A remaining challenge is the lower vaccine protective efficacy observed in children in low-and middle-income countries (LMICs) where the mortality and hospitalizations due to severe rotavirus disease still occur [1].The role of nutrition in influencing the immune response to a rotavirus vaccine is the focus of the accompanying paper by Isanaka and colleagues published in this issue of PLOS Medicine [2].Understanding why over 87% of children vaccinated with a rotavirus vaccine in low child mortality countries are protected against severe rotavirus disease compared to approximately 44% (27% to 59%) of children in high child mortality countries is not well understood [3].As an orally administered vaccine, initial focus has been on factors that could neutralize the live vaccine virus within the gut lumen.Most rotavirus vaccines are administered in a buffered formulation to reduce the risk of neutralization of the vaccine virus by gastric acid [4].In early clinical trials, fasting prior to vaccination was applied in an effort to reduce the potential impact of breast milk antibodies.This is now not considered necessary [5].A difference in the gut microbiome in infants from high-income and LMICs has been observed, although the administration of a probiotic did not result in improved rotavirus vaccine immunogenicity [6,7].Rotaviruses use histo-blood group antigens present on the gut epithelial surface in the initial phase of virus attachment and cellular entry [8].It has been proposed that population variability in histo-blood group antigen phenotype, specifically Lewis and secretor status, may explain the genotype diversity of rotavirus between regions and the responses observed to live oral rotavirus vaccines that may be VP4 [P] genotype dependent [8].Childhood malnutrition is associated with reduced immune responses to a range of infections, and in the immune response to vaccines, including rotavirus vaccines [9].Macro and/or micronutrient deficiencies have been linked to a range of abnormalities in T and B cell function, mucosal immunity, cytokine production, and responses [9].However, there are limited data on the impact of maternal nutritional supplements on the immune AU : Anabbreviationlisthasbeen responses following vaccination of their infants.Isanaka and colleagues' cluster-randomized study was nested within a double-blind, placebo control vaccine efficacy trial.It evaluated the effect of 3 different maternal nutritional supplements on serum antirotavirus immunoglobulin A (IgAAU : Pleasenoteth )