Prevalence and Age-Related Acquisition of Antibodies against Group A Streptococcal M-Related Proteins
Group A streptococcal (GAS) infections are common in children but less common in adults. Immunity against type-specific M proteins of GAS protects against subsequent infection with the same M type. The relative resistance of adults to infection has been attributed to immunity to multiple M types, among other factors. An additional explanation is immunity to cross-protective GAS antigens that provides broader protection later in life. M-related proteins (Mrp) of GAS are expressed by 83% of GAS isolates and they contain protective epitopes. Unlike M proteins, Mrp’s are highly conserved and are grouped into three structurally related families represented by Mrp2, 4, and 49. In the current study we evaluated the prevalence and age-related acquisition of Mrp antibodies in children.
Serum samples from 356 subjects (ages 1-16) were obtained from the clinical laboratories of a pediatric hospital. Purified, recombinant N-terminal peptides of Mrp2, Mrp4, and Mrp49 were used to assess Mrp antibody levels by ELISA. Human Mrp antibodies were purified by affinity chromatography and used in bactericidal tests.
Significant levels of antibodies against any of the three Mrp's were observed in 175/356 serum samples (49%). Mrp4 antibodies were the most prevalent (145/356), followed by Mrp 2 (88/356) and Mrp49 (73/356). There was a clear association between the subjects' age and prevalence of antibodies against all three Mrp's (r=0.32, p<0.001). Significant age-related trends were also observed for antibody levels against each individual Mrp peptide. Mrp4 antibodies affinity purified from human serum resulted in 99% killing of heterologous serotype M28 GAS.
Mrp antibodies are prevalent and are acquired in an age-related manner. Purified human antibodies against Mrp4 were strongly bactericidal. Taken together with our recent studies showing that Mrp’s have relatively conserved sequences comprising three structurally related families and that all three contain opsonic epitopes, our results suggest that Mrp antibodies in combination with M antibodies may contribute to the relative resistance to GAS infections later in life. These findings also have implications for the development of broadly protective GAS vaccines.
T. Penfound, None
J. Dale, Vaxent, LLC: Board Member, Member and Shareholder, Equity