High Diversity of Group A Streptococcal emm Types in an Indian Community: The Need to Tailor Multivalent Vaccines

Abstract

Background. Concern about the emergence of antibiotic-resistant strains and about morbidity and/or mortality related to rheumatic fever and rheumatic heart disease has been a continuous impetus for the development of a safe, effective vaccine against group A Streptococcus (GAS). To date, >120 GAS M types are known, as identified by serological typing. In general, serum immunoglobulin G directed to the hypervariable NH2 terminal portion of M protein leads to complement fixation and opsonophagocytosis of the homologous streptococcal serotype by polymorphonuclear leukocytes, and the protection is type specific. The sequence variation at the N terminus ultimately affects the binding of opsonic antibodies. Because of hypervariability in these opsonic sequences from different M types, it was relevant to use epitopes derived from these multiple sequences in a “multivalent vaccine” design for evaluation of protection against these M types of GAS. Thus, any attempts to design vaccines for a given community will require information on N terminal—sequence typing and variation. Methods. In the present study, we performed molecular characterization of isolates recovered from patients in northern India—to our knowledge, for the first time—in an attempt to study the circulating M types and their N terminal sequence variability. Results. We report tremendous diversity in GAS strains recovered from symptomatic patients, with implications on the design of appropriate vaccines. Fifty-nine isolates represented 33 different sequence types. Very few novel types and no predominant clones were found. Conclusions. The high diversity of emm types encountered in a single year suggests that any M protein—based multivalent vaccine would have to be specifically tailored for this region.