Antibodies to the conserved region of the M protein and a streptococcal superantigen cooperatively resolve toxic shock-like syndrome in HLA-humanized mice
Manisha Pandey, Ainslie Calcutt, Victoria Ozberk, Zhenjun Chen, Matthew Croxen, Jessica Powell, Emma Langshaw, Jamie-Lee Mills, Freda E-C Jen, James McCluskey, Jenny Robson, Gregory J Tyrrell, Michael F Good
SCIENCE ADVANCES | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019
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 inflamm..View full abstract
Awarded by National Health and Medical Research Council, Australia
This work was supported by grants from the National Health and Medical Research Council, Australia (grant nos. APP1037304 and APP1083548); National Foundation of Medical Research and Innovation (NFMRI, Australia); and an Australian Tropical Medicine Commercialization grant.