Abstract Introduction The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain-specific or more broadly protective. Here, we quantified the opsonic antibody response following invasive S. pyogenes infection. Materials and Methods Four patients with S. pyogenes bacteremia between 2018-2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute and convalescent sera were obtained, and the S. pyogenes isolates were genome-sequenced ( emm 118, emm 85, and two emm 1). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Results Antibody binding increased modestly against the infecting isolate and across emm types in convalescent compared to acute sera for all patients. For two patients, phagocytosis increased in convalescent serum for both the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Conclusion Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both non-functional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections.

Invasive streptococcal infection can lead to the generation of cross-strain opsonic antibodies