title: A synthetic M protein peptide synergizes with a CXC chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia.
abstract: Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain's ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100-1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and michael.good@griffith.edu.au m.pandey@griffith.edu.au.
authors.forename: Manisha
authors.initials: M
authors.lastname: Pandey
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and.
authors.forename: Emma
authors.initials: E
authors.lastname: Langshaw
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and.
authors.forename: Jon
authors.initials: J
authors.lastname: Hartas
authors.affiliation: Griffith Medical School, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Alfred
authors.initials: A
authors.lastname: Lam
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and michael.good@griffith.edu.au m.pandey@griffith.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D016470:Bacteremia; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D007156:Immunologic Memory; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011711:Pyoderma / Q000473:pathology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology; D013207:Staphylococcal Skin Infections / Q000473:pathology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000235:genetics / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D010455:Peptides; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic; C014689:streptococcal M protein