Development of a recombinant fusion protein vaccine formulation to protect against Streptococcus pyogenes.
Diseases resulting from infection by group A streptococcus (GAS) are an increasing burden on global health. A novel vaccine was developed targeting infection by Streptococcus pyogenes. The vaccine incorporates a recombinant fusion protein antigen (SpeAB) which was engineered by combining inactive mutant forms of streptococcal pyrogenic exotoxin A (SpeA) and streptococcal pyrogenic exotoxin B (SpeB) from S. pyogenes. A rational, scientific approach to vaccine development was utilized to determine optimal formulation conditions with aluminum adjuvants. Investigations of the pH stability profile of SpeAB concluded the antigen was most stable near pH 8. Incorporation of the stabilizers sucrose and mannitol significantly enhanced the stability of the antigen. Vaccines were formulated in which most of the SpeAB was adsorbed to the adjuvant or remained in solution. A SpeAB vaccine formulation, stabilized with sucrose, in which the antigen remains adsorbed to the aluminum adjuvant retained the greatest potency as determined by evaluation of neutralizing antibody responses in mice. This vaccine has great potential to provide a safe and effective method for prevention of GAS disease.
VaxForm, LLC, Bethlehem, PA 18015 United States. Electronic address: garry.morefield@vaxform.com.
Garry
G
Morefield
VaxForm, LLC, Bethlehem, PA 18015 United States.
Graham
G
Touhey
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907 United States.
Fangjia
F
Lu
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907 United States.
Anisa
A
Dunham
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907 United States.
Harm
H
HogenEsch
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology; D005098:Exotoxins / Q000276:immunology; D005260:Female; D008565:Membrane Proteins / Q000276:immunology; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes; D064166:Vaccine Potency; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D005098:Exotoxins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C117980:SpeA protein, Streptococcus pyogenes; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic; C027951:erythrogenic toxin; D000536:Aluminum Hydroxide
Aluminum adjuvant; Group A strep; Streptococcus pyogenes; Vaccine formulation