Immunogenic peptide against group a Streptococcus

Inventors

Good, Michael F. • Pandey, Manisha • Batzloff, Michael Raymond

Assignees

Griffith University

Abstract

A modified p145 peptide having enhanced mucosal immunogenicity for use in eliciting a mucosal immune response to group A streptococcal bacteria in a mammal such as a human. Intramuscular administration of the modified p145 peptide may be particularly efficacious. An S2 peptide or variant may be co-administered with the modified p145 peptide to enhance the immune response.

Core Innovation

The invention provides a p145-based synthetic immunogenic peptide directed to group A Streptococcus, and further defines a minimal epitope. The approach enhances the peptide by targeted amino-acid substitutions, including N at residue 13 and R at residue 17 of SEQ ID NO:3, where p*17 is defined by SEQ ID NO:1. The concept is presented in the context of nucleic acids encoding the immunogenic protein sequences, including SEQ ID NO:1 and SEQ ID NO:21, or conjugates of either with a carrier protein.

The invention reports that single-dose immunization, particularly intramuscular administration, elicits a mucosal immune response against group A Streptococcus. The mucosal immune response is characterized primarily by IgG with minimal or absent IgA. The disclosed immune outcome is linked to strong protection against skin infection and invasive disease, including hypervirulent CovR/S mutant strains.

The disclosure additionally provides combination use with a SpyCEP immunogenic fragment, including the S2 peptide or a variant such as K4S2. Supportive observations are described, including peptide library screening, antibody affinity and binding to GAS, challenge efficacy in mice, and molecular dynamics simulations indicating structural or helical stability differences versus p145/J8.

Claims Coverage

The independent claim set comprises two independent methods, each covering intramuscular administration of an isolated nucleic acid encoding an immunogenic protein defined by specified amino-acid sequences, optionally conjugated to a carrier protein, with the claimed immunological focus on mucosal immunity against group A streptococcal bacteria or infection.

Across both independent claims, the core coverage is intramuscular administration of an isolated nucleic acid encoding a protein defined by SEQ ID NO: 1 and/or SEQ ID NO: 21, including conjugates with a carrier protein, for inducing or eliciting mucosal immune responses against group A streptococcal bacteria or infection.

Stated Advantages

Documented Applications