Heterogeneity of community based pediatric GAS isolates from India: Challenges to the multivalent vaccine approach

Abstract

The objective of present study was to find the types of GAS strains circulating in the pediatric population and to assess the immunogenicity of peptides corresponding to N-terminal sequence of M-protein for vaccine development. GAS strains (n = 298) were isolated from children with and without pharyngitis/impetigo during a cross-sectional survey conducted by two centres in North and South India in 8026 school children (5 to 14 years age group). The strains were emm typed and the synthetic peptides corresponding to N-terminal amino acid sequence were tested for their immunogenicity in Balb/c mice. The emm-typing of 71 GAS isolates from North India and 227 strains from South India showed prevalence of 14 and 59 different emm types, showing high heterogeneity of these strains. Among the predominant emm types in Northern and Southern India, only emm type 11 was common. The antipeptide sera raised against few of these peptides were found to offer minimal cross protection against heterologous strains. With an exception of few emm types, the others circulating in India are different from that of the US in both type and frequency, implying that an N-terminal variable region-based vaccine, designed based on emm sequence of the strains prevalent in western populations, may not be effective in India. Also, the greater degree of heterogeneity and regional differences noted in the emm types circulating in the community and minimal cross-protection against heterologous strains poses challenges to the development of N-terminal-based multivalent vaccine pointing to an urgent need for identifying an effective strategy for vaccine development in India.