Serological Responses to Target Streptococcus pyogenes Vaccine Antigens in Patients With Proven Invasive β-Hemolytic Streptococcal Infections

Background:
Rising incidence of invasive β-hemolytic streptococcal (iBHS) infections has prompted consideration of vaccination as a preventative strategy for at-risk populations. The benefits of a vaccine targeting Lancefield group A (Streptococcus pyogenes; Strep A) would increase if cross-species immunity against Lancefield groups C/G (Streptococcus dysgalactiae subspecies equisimilis; SDSE) and B (Streptococcus agalactiae; GBS) was demonstrated.

Methods:
A prospective, observational study of adult patients with iBHS infections due to Strep A, SDSE, or GBS. Antibody responses to 6 Strep A candidate antigens were assayed on acute and convalescent sera. A serological response was defined as an increase of >0.2 log10 arbitrary units/mL (AU/mL).

Results:
Sixty-seven participants were enrolled. Thirty-three participants were included in the final analysis (12, 11, and 10 with Strep A, SDSE, and GBS, respectively). The median serological response for participants with Strep A was significant for all tested antigens (median >0.2 log10 difference between acute and convalescent samples; P < .05 for all). Those with SDSE had comparable and significant median responses to streptolysin-O (0.65 log10 AU/mL; interquartile range [IQR], 0.36–1.67; P = .004), S. pyogenes adhesion and division protein (0.68 log10 AU/mL; IQR, 0.36–1.63; P = .005), and C5a peptidase (ScpA; 0.30 log10 AU/mL; IQR, 0.23–1.06; P = .004). GBS responses were limited to ScpA only (0.34 log10 AU/mL; IQR, 0.08–0.52; P = .05).

Conclusions:
Patients with invasive Strep A infection mount robust antibody responses to 6 non-M protein vaccine candidate antigens. Similar significant responses to C5a peptidase in those with invasive SDSE and GBS infection highlight the importance of further research into cross-species protection and immunological correlates of vaccine efficacy.