title: M protein conserved region antibodies opsonise multiple strains of Streptococcus pyogenes with sequence variations in C-repeats.
abstract: The development of a group A streptococcal (GAS) vaccine has focused on the M protein, a major virulence factor. Antibodies against the amino terminal domain of the M protein are generally protective but only provide type-specific immunity. J14, a 29-mer peptide sequence which contains a conserved epitope from the C-repeat region of the M protein, offers the possibility of a vaccine which will elicit protective opsonic antibodies against multiple GAS strains. In this study we have shown that antibodies raised against J14 are capable of opsonising 37 GAS isolates representing different emm types derived from a region in which GAS infection is endemic. We also demonstrate that J14 antisera is capable of opsonising GAS isolates containing J14 homologues but not J14-specific sequences, further increasing the strain coverage of this vaccine candidate. Isolates with three C-repeats were opsonised more efficiently than isolates with two repeats. Opsonisation of a strain with only a single C-repeat was dramatically lower than other strains tested. The number of C-repeats present in the M protein of individual isolates therefore appears to be the critical factor in determining bactericidal capacity of J14 antisera. The reduced opsonic capacity of sera against this strain was shown to correlate with a reduced capacity to bind J14 antisera, as demonstrated by immunofluorescence microscopy and FACS analysis. In vivo challenge experiments also confirmed the protective efficacy of immunisation with J14 peptide.
authors.affiliation: Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh 160012, India. hvohra@rediffmail.com
authors.forename: Harpreet
authors.initials: H
authors.lastname: Vohra
authors.forename: Nilay
authors.initials: N
authors.lastname: Dey
authors.forename: Shivali
authors.initials: S
authors.lastname: Gupta
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: David
authors.initials: D
authors.lastname: McMillan
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007114:Immunization; D007194:India / Q000453:epidemiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000276:immunology*; D013290:Streptococcal Infections / Q000453:epidemiology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000737:chemistry; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000302:isolation & purification; D020079:Terminal Repeat Sequences
chemical_list: D000907:Antibodies, Bacterial; D006023:Glycoproteins; D007106:Immune Sera; D009895:Opsonin Proteins; D022541:Streptococcal Vaccines; C023587:protein M (glycoprotein)