Funding: Support for this project was provided by Program for Appropriate Technology in Health (PATH) through funding from the Global Alliance for Vaccines and Immunisation (GAVI). The views expressed by the authors do not necessarily reflect the views of GAVI and/or PATH. The authors were personally salaried by their institutions during the period of writing of this paper. “
“Diarrheal selleckchem disease is the second leading cause of under-five mortality worldwide [1] and [2]. Rotavirus is the most common cause of severe diarrheal disease in young children globally, attributing to >25 million clinic visits, an estimated 2 million hospitalizations, and approximately 527,000

deaths of children under 5 each year [3], [4] and [5]. By the age of five, nearly every child in both developed and developing countries will contract rotavirus [5]; however, the great proportion of the burden of rotavirus is borne by young children in developing countries. In Africa and Asia, >75% of infants will have contracted their first serious rotavirus infection by 12 months of age and approximately 86% of the global mortality due to rotavirus occurs in these settings [4] and [5]. Furthermore, three countries in the Indian subcontinent (India, Bangladesh, and Pakistan) account for >30% (N = 160,000–200,000) of all rotavirus-related deaths worldwide [4], [6],

[7] and [8]. This large burden of disease also creates an overwhelming economic burden on developing-country populations. For example, average expenditures per case treated in selleck chemicals llc Vellore, India, came to 5.8% (large hospital) and 2.2% (small hospital) of the household annual income [8]. Symptomatic rotavirus presents itself most commonly as acute watery diarrhea, forceful vomiting, fever, TCL and dehydration [9] and [10]. Rotavirus is highly contagious and resilient, and improvements to water and sanitation do not adequately

prevent its transmission [5], [11] and [12]. Malnutrition or co-infection with multiple enteric pathogens, common in developing countries, can further hinder effective rotavirus treatment, delay recovery, and lead to further sequelae, such as growth and developmental delays and susceptibility to re-infection. Therefore, prevention of rotavirus through immunization is considered a global priority to manage the disease [5] and [13]. Rotavirus vaccine development was influenced early by the observation that, due to the variety of strains circulating, a rotavirus vaccine needed to show heterotypic protection against the circulating strains to correctly assess the clinical efficacy [14]. The important antigenic characteristics of rotavirus strains are defined by two neutralizing antigens on the outer capsid – VP4 (a protease-sensitive protein protruding from the surface and labeled as the P-type) and VP7 (an outer capsid glycoprotein labeled as the G-type) [14].