M protein conserved region antibodies opsonise multiple strains of Streptococcus pyogenes with sequence variations in

Harpreet Vohra1, Nilay Dey, Shivali Gupta

  • 1Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh 160012, India. hvohra@rediffmail.com

Insights

A novel vaccine peptide, J14, targeting the group A streptococcal M protein, elicits protective antibodies against multiple strains. Antibody efficacy depends on the number of C-repeats in the M protein, crucial for opsonisation and bacterial clearance.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccine Development

Background:

  • Group A Streptococcus (GAS) causes significant infections, with M protein as a key virulence factor.
  • Current GAS vaccines targeting M protein N-terminal domains offer type-specific immunity.
  • A conserved epitope in the M protein C-repeat region presents an opportunity for broad-spectrum vaccine candidates.

Purpose of the Study:

  • To evaluate the J14 peptide as a potential vaccine candidate for group A Streptococcus.
  • To determine the breadth of opsonising antibody activity elicited by J14 against diverse GAS strains.
  • To investigate the role of M protein C-repeats in J14-mediated opsonisation and protection.

Main Methods:

  • Immunisation of subjects with the J14 peptide.
  • Testing J14-induced antibodies for opsonisation of GAS isolates representing various emm types.
  • Assessing antibody binding to GAS using immunofluorescence microscopy and FACS analysis.
  • Conducting in vivo challenge experiments to confirm protective efficacy.

Main Results:

  • Antibodies against J14 effectively opsonised 37 GAS isolates from an endemic region.
  • J14 antisera opsonised strains with J14 homologues, expanding strain coverage.
  • Opsonisation efficiency correlated with the number of C-repeats in the M protein; fewer repeats reduced efficacy.
  • Reduced opsonisation correlated with decreased antibody binding to GAS strains with fewer C-repeats.
  • In vivo studies confirmed the protective effect of J14 peptide immunisation.

Conclusions:

  • The J14 peptide is a promising vaccine candidate for group A Streptococcus, inducing broadly protective opsonic antibodies.
  • The number of C-repeats in the M protein is a critical determinant of J14-mediated bactericidal activity.
  • J14 peptide vaccination demonstrates protective efficacy in vivo, supporting its further development.

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