title: Immunogenicity in mice and non-human primates of the Group A Streptococcal J8 peptide vaccine candidate conjugated to CRM197.
abstract: Vaccine development for Group A streptococcal (GAS) infection has been extensively focused on the N-terminal hypervariable or the C-terminal conserved regions of the M protein, a major virulence factor of GAS. We evaluated the immunogenicity and functional activity of the conserved C-terminal peptide vaccine candidate, J8, conjugated to CRM197, in two mouse strains: C3H (H2(k)) and Balb/c (H2(d)), and in rhesus macaques. Mice were immunized with J8-CRM197 formulated with Amorphous Aluminum Hydroxyphosphate Sulfate Adjuvant (AAHSA), and non-human primates were immunized with J8-CRM197 formulated with AAHSA, ISCOMATRIX (TM) adjuvant, or AAHSA/ISCOMATRIX adjuvant. J8-CRM197 was immunogenic in mice from both H2(k) and H2(d) backgrounds, and the antibodies generated bound to the surface of four different GAS serotypes and had functional bacterial opsonic activity. Mice immunized with J8-CRM197/AAHSA demonstrated varying degrees of protection from lethal challenge. We also demonstrated that J8-CRM197 is immunogenic in non-human primates. Our data confirm the utility of J8 as a potential GAS vaccine candidate and demonstrate that CRM197 is an acceptable protein carrier for this peptide.
authors.affiliation: Merck Research Labs; Merck & Co. Inc; West Point, PA, USA.
authors.forename: Ivette
authors.initials: I
authors.lastname: Caro-Aguilar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ottinger
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hepler
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Nahas
authors.forename: Chengwei
authors.initials: C
authors.lastname: Wu
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: Michael
authors.initials: M
authors.lastname: Batzloff
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Joyce
authors.forename: Jon H
authors.initials: JH
authors.lastname: Heinrichs
authors.forename: Julie M
authors.initials: JM
authors.lastname: Skinner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008253:Macaca mulatta; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C028581:CRM197 (non-toxic variant of diphtheria toxin)