Background:
Streptococcus A (StrepA) is a globally important pathogen for which there is no licenced vaccine. Understanding the natural, protective immune response to the pathogen will inform the development of an effective vaccine. However, the basis of population immunity to StrepA is poorly understood. The most widely used assays for assessing the protective capacity of sera are known as “Lancefield” bactericidal assays. These assays were developed in the 1950s and are not suitable for contemporary vaccine programmes, which require an assay that is quantitative, reproducible and high-throughput.
Methods:
We have studied the natural antibody response developed to StrepA using pooled human intravenous immunoglobulin G (IVIG), combined with our newly developed StrepA opsonophagocytic killing assay (OPKA). The IVIG is purified from over one thousand healthy donors, and is therefore a meaningful surrogate of population wide immunity. We optimised the OPKA for StrepA strains that are representative of the three major StrepA pattern-types; M12 (A-C pattern), M53 (D pattern) and M75 (E pattern).
Results:
While IVIG is capable of killing each of these StrepA strains, specificity assays showed the profile of protective antibodies differs for each strain. The M protein is a key virulence factor and the basis of leading StrepA vaccines. Interestingly, antibodies targeting M protein were a major component of the IVIG protective antibody repertoire for M12, intermediate for M53, but not for M75.
Conclusion:
In summary, contemporary bactericidal assays provide a robust means to map the protective StrepA immune response, with notable differences in the contribution of M protein antibodies to opsonophagocytosis across the three major pattern types.