Antibodies to the conserved region of the M protein and a streptococcal superantigen cooperatively resolve toxic shock-like syndrome in HLA-humanized mice

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Pandey, M; Calcutt, A; Ozberk, V; Chen, Z; Croxen, M; Powell, J; Langshaw, E; Mills, J-L; Jen, FE-C; McCluskey, J; ...Date
2019-09-01Source Title
SCIENCE ADVANCESPublisher
AMER ASSOC ADVANCEMENT SCIENCEAffiliation
Microbiology and ImmunologyChancellery Research
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Pandey, M., Calcutt, A., Ozberk, V., Chen, Z., Croxen, M., Powell, J., Langshaw, E., Mills, J. -L., Jen, F. E. -C., McCluskey, J., Robson, J., Tyrrell, G. J. & Good, M. F. (2019). Antibodies to the conserved region of the M protein and a streptococcal superantigen cooperatively resolve toxic shock-like syndrome in HLA-humanized mice. SCIENCE ADVANCES, 5 (9), https://doi.org/10.1126/sciadv.aax3013.Access Status
Open AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726444Abstract
Invasive streptococcal disease (ISD) and toxic shock syndrome (STSS) result in over 160,000 deaths each year. We modelled these in HLA-transgenic mice infected with a clinically lethal isolate expressing Streptococcal pyrogenic exotoxin (Spe) C and demonstrate that both SpeC and streptococcal M protein, acting cooperatively, are required for disease. Vaccination with a conserved M protein peptide, J8, protects against STSS by causing a dramatic reduction in bacterial burden associated with the absence of SpeC and inflammatory cytokines in the blood. Furthermore, passive immunotherapy with antibodies to J8 quickly resolves established disease by clearing the infection and ablating the inflammatory activity of the M protein, which is further enhanced by addition of SpeC antibodies. Analysis of 77 recent isolates of Streptococcus pyogenes causing ISD, demonstrated that anti-J8 antibodies theoretically recognize at least 73, providing strong support for using antibodies to J8, with or without antibodies to SpeC, as a therapeutic approach.
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