title: Vaccination with Streptococcus pyogenes nuclease A stimulates a high antibody response but no protective immunity in a mouse model of infection.
abstract: Streptococcus pyogenes is a human pathogen which causes a spectrum of diseases ranging from pharyngitis to rheumatic fever, necrotising fasciitis and toxic shock syndrome. Development of a vaccine for S. pyogenes has been confounded both by the diversity of the disease-causing serotypes and the spectre of inadvertently stimulating autoimmunity. The S. pyogenes nuclease A (SpnA) is a recently characterised virulence factor that is highly conserved across strains and expressed during human disease. Deletion of spnA from S. pyogenes results in reduced survival of bacteria in whole human blood and attenuated virulence in a mouse model of infection. Collectively these features suggest that SpnA has potential as a vaccine candidate for S. pyogenes. Mice vaccinated subcutaneously with single or multiple doses of recombinant SpnA emulsified in Incomplete Freund's Adjuvant developed a robust and durable IgG response, including neutralising activity, to this protein. However, vaccination with rSpnA conferred no advantage in terms of lesion development, disease symptoms or colonisation levels after a sub-lethal subcutaneous challenge with S. pyogenes. Anti-SpnA serum IgG responses and neutralising activity were increased in response to challenge, indicating that SpnA is expressed in vivo. SpnA is unlikely to be a suitable antigen for a vaccine against S. pyogenes.
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences and Maurice Wilkins Centre for Biodiscovery, University of Auckland, Auckland, 1142, New Zealand, f.radcliff@auckland.ac.nz.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Radcliff
authors.forename: John D
authors.initials: JD
authors.lastname: Fraser
authors.forename: Thomas
authors.initials: T
authors.lastname: Proft
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation; D003851:Deoxyribonucleases / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; D037521:Virulence Factors; D005620:Freund's Adjuvant; D003851:Deoxyribonucleases