Serological responses to target Streptococcus pyogenes vaccine antigens in patients with proven invasive beta-haemolytic streptococcal infections

Kristyn Langworthy; Michael Taggart; Rosemary Smith; Avram Levy; Daniel R Knight; Siong Hui; Alma Fulurija; Michael Morici; Edward Raby; Laurens Manning

doi:10.1093/infdis/jiae496

Serological responses to target Streptococcus pyogenes vaccine antigens in patients with proven invasive beta-haemolytic streptococcal infections

J Infect Dis. 2024 Oct 9:jiae496. doi: 10.1093/infdis/jiae496. Online ahead of print.

Authors

Kristyn Langworthy¹, Michael Taggart¹, Rosemary Smith², Avram Levy^{3

4}, Daniel R Knight^{3

4}, Siong Hui^{1

5}, Alma Fulurija^{6

7}, Michael Morici^{6

7}, Edward Raby^{1

8}, Laurens Manning^{1

6

7

9}

Affiliations

¹ Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group, Murdoch, Western Australia, Australia, 6150.
² General Medicine Department, Rockingham General Hospital, Cooloongup, Western Australia, 6168.
³ School of Biomedical Science, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Western Australia, Australia, 6009.
⁴ Department of Microbiology, PathWest Laboratory Medicine, QEII, Nedlands, Western Australia, Australia, 6150.
⁵ Curtin Medical School, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6845.
⁶ Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia, 6009.
⁷ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia, 6009.
⁸ Department of Microbiology, PathWest Laboratory Medicine, Fiona Stanley Hospital, Murdoch, Western Australia, Australia, 6150.
⁹ Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Western Australia, Australia, 6009.

PMID: 39383256
DOI: 10.1093/infdis/jiae496

Abstract

Background: Rising incidence of invasive beta-haemolytic 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 six Strep A candidate antigens were assayed on acute and convalescent sera. A serological response was defined as an increase of >0.2log10 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 >0.2log10 difference between acute and convalescent samples; P<0.05 for all). Those with SDSE had comparable and significant median (IQR) responses to streptolysin-O (0.65 [0.36-1.67], P=0.004), S. pyogenes adhesion and division protein (0.68 [0.36-1.63], P=0.005) and C5a peptidase (ScpA; 0.30 [0.23-1.06]), P=0.004). GBS responses were limited to ScpA only (0.34 [0.08-0.52], P=0.05).

Conclusion: Patients with invasive Strep A infection mount robust antibody responses to six 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.

Keywords: Streptococcus dysgalactiae subspecies equisimilis; Beta haemolytic streptococci; group A streptococcus; group B streptococcus; serology; streptococci.

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