Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein

J Infect Dis. 2006 Aug 1;194(3):316-24. doi: 10.1086/505580. Epub 2006 Jun 30.

Abstract

Background: We investigated the lipid core peptide (LCP) system for mucosal vaccine delivery against infection with group A streptococcus (GAS)--the causative pathogen of rheumatic fever and rheumatic heart disease.

Methods: An LCP vaccine formulation containing 2 different peptide epitopes of the antiphagocytic M protein of GAS--a conformational epitope from the carboxyterminal conserved C-repeat region and an aminoterminal serotypic epitope--was intranasally administered to mice with cholera toxin B subunit or without additional adjuvant.

Results: Our data demonstrate that the LCP vaccine formulation induced the elicitation of antigen-specific systemic immunoglobulin G responses when administered with or without cholera toxin B subunit, whereas cholera toxin B subunit was required for the induction of antigen-specific mucosal immunoglobulin A responses. Immune serum samples from vaccinated mice were capable of opsonization of a homologous GAS strain, as well as opsonization of a heterologous GAS strain. Furthermore, mice were protected from GAS challenge following immunization with the LCP vaccine formulation, even in the absence of additional adjuvant.

Conclusions: These data support the potential of the LCP system in the development of a self-adjuvanting, synthetic, peptide-based mucosal GAS vaccine for the prevention of diseases caused by GAS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Administration, Intranasal
  • Administration, Oral
  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology*
  • Bacterial Outer Membrane Proteins / immunology*
  • Carrier Proteins / immunology*
  • Diphtheria Toxoid / administration & dosage
  • Diphtheria Toxoid / immunology
  • Drug Delivery Systems / methods
  • Epitopes / immunology
  • Immunity, Mucosal / immunology
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunotherapy, Active / methods*
  • Lipids / administration & dosage*
  • Lipids / chemistry
  • Lipids / immunology
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Streptococcal Infections / immunology
  • Streptococcal Infections / prevention & control
  • Streptococcal Vaccines / administration & dosage*
  • Streptococcal Vaccines / immunology
  • Streptococcus pyogenes / immunology
  • Vaccines, Subunit / administration & dosage*
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Carrier Proteins
  • Diphtheria Toxoid
  • Epitopes
  • Immunoglobulin A
  • Immunoglobulin G
  • Lipids
  • Peptide Fragments
  • Streptococcal Vaccines
  • Vaccines, Subunit
  • streptococcal M protein