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Abstract

Phase I Trial of a Peptide-Based Vaccine to Prevent Group A Streptococcal Infection †

by
Michael F. Good
1,*,
Manisha Pandey
1,
Simone Reynolds
1,
Victoria Ozberk
1,
Vanessa Meier-Stephenson
2,
Michael Hawkes
3,
Ailin Lepletier
1,
Ainslie Calcutt
1,
Christie Short
1,
Ijeoma Ogbuehi
4,
Alena Tse-Chang
3,
Catherine Burton
3,
Kelly Kim
4,
Conar O’Neil
4,
William Stokes
5,
Maryna Yaskina
6,
Ben Tyrrell
6,
Scott Jamieson
4,
Eloise Keeffe
1,
Chris Davis
1,
Joshua Osowicki
7,
Andrew Steer
7,
Greg Tyrrell
5,
D. Lorne Tyrrell
8 and
Michael Houghton
8add Show full author list remove Hide full author list
1
Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD 4215, Australia
2
Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, AB T6G 2G5, Canada
3
Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2G5, Canada
4
Clinical Trials Office, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2C8, Canada
5
Department Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB T6G 2G5, Canada
6
Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2G5, Canada
7
Murdoch Children’s Research Institute, Melbourne, VIC 3052, Australia
8
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2G5, Canada
*
Author to whom correspondence should be addressed.
†
Presented at the 22nd Lancefield International Symposium on Streptococci and Streptococcal Diseases, Brisbane, Australia, 1–5 June 2025.
Proceedings 2025, 124(1), 26; https://doi.org/10.3390/proceedings2025124026
Published: 17 September 2025
(This article belongs to the Proceedings of The 22nd Lancefield International Symposium on Streptococci and Streptococcal Diseases (LISSSD 2025))
Versions Notes

We identified minimal conserved epitopes on the M-protein (J8, P*17) and the anti-neutrophil chemoattractant virulence factor, SpyCEP (K4S2), of Streptococcus pyogenes (‘Strep A’) as targets of protective antibodies. Vaccines combining either M-protein, epitope and K4S2 induce murine antibodies that bind M-protein neutralize SpyCEP and protect the upper respiratory tract and skin against all Strep A strains that we studied. Although the vaccine epitopes are cryptic and not recognized in naive mice following infection, infection of vaccinated mice leads to antibody boosting and enhanced protection, suggesting that vaccine-induced immunity will be long-lasting and significantly improve over time.
Thirty healthy adult volunteers were recruited by The North Alberta Clinical Trials and Research Centre. Three doses of each of two GMP-grade vaccines (J8-CRM197/K4S2-CRM197/Alum; P*17-CRM197/K4S2-CRM197/Alum) or placebo (rabies vaccine, RabAvert) were administered to volunteers at 0, 3, and 6 weeks. The first 10 volunteers (five for each vaccine candidate) to receive the vaccines were assessed. There were no attributable high-grade adverse events. The remaining volunteers will be assessed following unblinding of those cohorts.
Both vaccines demonstrated strong immunogenicity in all participants. A competitive binding assay was established and demonstrated binding of vaccine-induced antibodies to the surface of multiple Strep A strains in all vaccinated participants up to 6 months. Antibody avidity increased with sequential vaccinations. Vaccine-induced antibodies could kill Strep A in an in vitro opsonophagocytic assay and protected IL-8 from SpyCEP-mediated proteolysis. We plan to advance this vaccine into a Phase Ib challenge trial, followed by a Phase II paediatric trial.

Author Contributions

Conceptualization, M.F.G., M.P., S.R., V.O., A.L., A.C., C.S., E.K., C.D., V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T., J.O., A.S. and M.H. (Michael Houghton); Methodology, M.P., S.R., V.O., A.L., A.C., C.S., E.K., C.D., V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T., J.O. and A.S.; Investigation, V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T. and S.J.; Data Curation, V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T. and S.J.; Writing—original draft preparation, M.F.G., M.P., S.R., V.O., A.L., A.C., C.S., E.K., C.D., V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T., J.O., A.S. and M.H. (Michael Houghton); Writing—review and editing, M.F.G., M.P., S.R., V.O., A.L., A.C., C.S., E.K., C.D., V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T., J.O., A.S. and M.H. (Michael Houghton); Project administration, V.M.-S., M.H. (Michael Hawkes), I.O., A.T.-C., C.B., K.K., C.O., W.S., M.Y., B.T., G.T., D.L.T. and S.J. All authors have read and agreed to the published version of the manuscript.

Funding

National Heart Foundation (Australia); Li Ka Shing Institute of Virology; National Health and Medical Research Council (Australia).

Institutional Review Board Statement

The University of Alberta Human Research Ethics Board (HREB) has assessed and approved this protocol (REB Pro00089919, ver. 5, October 2023).

Informed Consent Statement

The University of Alberta Human Research Ethics Board (HREB) has assessed and approved the consent form and all trial-related documents. Written informed consent to participate was obtained from all participants.

Data Availability Statement

The data for this trial can be supplied on request from the clinical lead (VMS) and scientific lead (MG),and approval from the Research Ethics Board.

Conflicts of Interest

The authors declare no conflict of interest.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Good, M.F.; Pandey, M.; Reynolds, S.; Ozberk, V.; Meier-Stephenson, V.; Hawkes, M.; Lepletier, A.; Calcutt, A.; Short, C.; Ogbuehi, I.; et al. Phase I Trial of a Peptide-Based Vaccine to Prevent Group A Streptococcal Infection. Proceedings 2025, 124, 26. https://doi.org/10.3390/proceedings2025124026

AMA Style

Good MF, Pandey M, Reynolds S, Ozberk V, Meier-Stephenson V, Hawkes M, Lepletier A, Calcutt A, Short C, Ogbuehi I, et al. Phase I Trial of a Peptide-Based Vaccine to Prevent Group A Streptococcal Infection. Proceedings. 2025; 124(1):26. https://doi.org/10.3390/proceedings2025124026

Chicago/Turabian Style

Good, Michael F., Manisha Pandey, Simone Reynolds, Victoria Ozberk, Vanessa Meier-Stephenson, Michael Hawkes, Ailin Lepletier, Ainslie Calcutt, Christie Short, Ijeoma Ogbuehi, and et al. 2025. "Phase I Trial of a Peptide-Based Vaccine to Prevent Group A Streptococcal Infection" Proceedings 124, no. 1: 26. https://doi.org/10.3390/proceedings2025124026

APA Style

Good, M. F., Pandey, M., Reynolds, S., Ozberk, V., Meier-Stephenson, V., Hawkes, M., Lepletier, A., Calcutt, A., Short, C., Ogbuehi, I., Tse-Chang, A., Burton, C., Kim, K., O’Neil, C., Stokes, W., Yaskina, M., Tyrrell, B., Jamieson, S., Keeffe, E., ... Houghton, M. (2025). Phase I Trial of a Peptide-Based Vaccine to Prevent Group A Streptococcal Infection. Proceedings, 124(1), 26. https://doi.org/10.3390/proceedings2025124026

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