Biology

Prof. Gagandeep Kang
Translational Health Science and Technology Institute, Faridabad

Oral rotavirus, polio and cholera vaccines are less immunogenic and less effective in children living in resource-poor regions of Africa and Asia. The lower efficacy of multiple oral vaccines in similar settings suggests there may be common mechanisms that limit immunity induced by oral vaccines in such environments.  Enteric immune responses in children arise, are maintained and regulated in a complex ecology in which age, maternal exposure, environment, enteric commensals, pathogens and vaccines interact in ways that are incompletely understood. Several potential biological barriers to oral vaccination have been proposed and investigated through both observational and interventional approaches with limited success.

In studies on oral rotavirus (ORV) and polio vaccines (OPV) in India, we have investigated the role of maternal antibodies, the presence of bacterial and viral pathogens, the intestinal microbiota, intestinal inflammation and the systemic and mucosal immune response in children from lower socio-economic status families. For ORV, high maternal antibodies and co-administration of OPV decreased immunogenicity, but there were no differences in the microbiota of responders and non- responders. For OPV, presence of viruses, particularly enteroviruses decreased vaccine response. A random forests model applied to multiple potential determinants of OPV immunogenicity showed that seroconversion correlated with changes in the cytokine milieu in plasma, ex vivo T-cell phenotype and response to poliovirus stimulation.  Inclusion of data on infant infections and immune parameters progressively improved the ability to predict seroconversion to 80%. The ability to apply new investigative approaches to carefully conducted clinical studies in resource-poor settings can provide new insights into the heterogeneous performance of oral vaccines.