ABSTRACT
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX®) vaccine-induced responses in Zambia. We studied 135 mother-infant pairs under a rotavirus vaccine clinical trial, with infants aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months, though no statistically significant difference was observed between the study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGAs were associated with RV vaccine immunogenicity at 12 months as opposed to in early infant life. Further investigation into the low efficacy of ROTARIX® and appropriate intervention is key to unlocking the full vaccine benefits for U5 children.
ABSTRACT
ABSTRACT ABO, H, secretor and Lewis histo-blood system genes control the expression of part of the carbohydrate repertoire present in areas of the body occupied by microorganisms. These carbohydrates, besides having great structural diversity, act as potential receptors for pathogenic and non-pathogenic microorganisms influencing susceptibility and resistance to infection and illness. Despite the knowledge of some structural variability of these carbohydrate antigens and their polymorphic levels of expression in tissue and exocrine secretions, little is known about their biological importance and potential applications in medicine. This review highlights the structural diversity, the biological importance and potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.
Subject(s)
ABO Blood-Group System , Lewis Blood Group Antigens , Oligosaccharides , Carbohydrates , GlycosyltransferasesABSTRACT
ABO, H, secretor and Lewis histo-blood system genes control the expression of part of the carbohydrate repertoire present in areas of the body occupied by microorganisms. These carbohydrates, besides having great structural diversity, act as potential receptors for pathogenic and non-pathogenic microorganisms influencing susceptibility and resistance to infection and illness. Despite the knowledge of some structural variability of these carbohydrate antigens and their polymorphic levels of expression in tissue and exocrine secretions, little is known about their biological importance and potential applications in medicine. This review highlights the structural diversity, the biological importance and potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.
ABSTRACT
Norovirus (NoVs) are recognized as a leading cause of human gastroenteritis worldwide. Infection takes place following ingestion of contaminated food or most often through direct contact from person to person. However, not all individuals are equally sensitive to these viruses. Indeed, NoVs use ABH and Lewis glycans of the histo-blood group antigen family (HBGAs) as ligands. At the epithelial level synthesis of these HBGAs requires the action of several glycosyltransferases encoded by the ABO, FUT2 and FUT3 genes. Since the attachment profile to these glycans varies from strain to strain, the combined polymorphism at these three loci dictates sensitivity to NoV infection. Studies of the NoV-HBGA interactions together with phylogenetic analyses and the epidemiologic follow-up of strains indicate that NoVs transmission and evolution depends both on the establishment of herd immunity and on the genetic resistance of many individuals that contributes to restrict NoVs circulation, confering a herd innate proctection.