Evaluation of Immune Responses to Rotavirus Vaccination in Indian Infants

Abstract

In 2008, World Health Organization (WHO) estimated that there were 1.24 million deaths due to diarrhea in children younger than 5 years. An estimated 453,000 children die from severe, dehydrating diarrhea caused by rotavirus. Further, in India alone, rotavirus diarrhea causes an estimated 12,000 - 153,000 deaths, 457,000 - 884,000 hospitalizations and 2 million outpatient visits among children lt5 years of age. Although two live, oral rotavirus vaccines are available, the efficacy of both has been comparatively low in developing countries, like other oral vaccines that have historically performed poorly in the developing world. The results of the studies reported here indicate that the bovine tetravalent rotavirus vaccine is safe and immunogenic and if taken further into clinical trials and licensure, is likely to be able to prevent a proportion of rotavirus disease in India. However, it is important to note that high dose vaccine was required to induce an immune response in a setting where levels of prior exposure were high. The data obtained by measuring rotavirus specific serum, fecal and salivary IgA in vaccinated infants showed that vaccine immunogenicity can be assessed in all three body fluids. However, more frequent sampling and an even more sensitive assay are necessary to assess the role of IgA in different body fluids as a measure of vaccine response. The information obtained from this study shows that breast milk IgA could protect neonates from rotavirus infection, although there was no effect on vaccination - these results may be strain and dose-specific and need further investigation. Comparison of 3 and 5 doses showed no difference in serum immune response to rotavirus among Indian infants. Supplementation with LGG has a positive immunomodulatory effect and that it could be useful in decreasing repeated episodes of rotavirus diarrhea. Taken together, these studies provide new information on antibody responses to rotavirus in Indian children and will form the base for further investigations.