Reynolds, Simone

Mohamed Rafeek, Rukshan Ahamed

Hamlin, Adam

Lepletier, Ailin

Pandey, Manisha

Ketheesan, Natkunam

Good, Michael F

2023-02-04

<p>We have developed a candidate vaccine to protect against multiple strains of <i>Streptococcus pyogenes</i> infections. The candidate vaccine contains two synthetic peptides derived from <i>S. pyogenes</i> proteins: the M-protein epitope, p*17 and the IL-8 degrading <i>S.pyogenes</i> Cell-Envelope Proteinase (SpyCEP) epitope, K4S2. In this study we utilise a rat autoimmune valvulitis model that displays both the cardiac and neurobehavioural pathology associated with post-streptococcal sequelae, to assess if the vaccine candidate antigens induce autoimmune complications and inflammatory pathology. Each antigen was conjugated to carrier protein diphtheria toxoid (DT) and independently assessed for potential to induce autoimmune pathology in female Lewis rats. Rats were administered three subcutaneous doses, and one intranasal dose over a four-week study with a two-week recovery period. A positive control group received recombinant <i>S. pyogenes</i> M5 (rM5) protein, and the negative control group received PBS. Rats that received rM5 developed significant cardiac and neurological pathologies. There was no evidence of these pathologies in the PBS control group, or the rats administered either P*17-DT or K4S2-DT. This study provides further preclinical evidence of the safety of the vaccine candidates p*17 and K4S2 and their appropriateness as candidates in human clinical trials.</p>

npj Vaccines, v.8, p. 1-10

2059-0105

https://hdl.handle.net/1959.11/69856

en

Nature Publishing Group

Attribution 4.0 International

Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model

Journal Article

Publication