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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Administration, Intranasal
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Administration, Oral
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Amino Acid Sequence
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Animals
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Antibodies, Bacterial / biosynthesis
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Antibodies, Bacterial / blood
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Antigens, Bacterial / immunology*
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Bacterial Outer Membrane Proteins / immunology*
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Carrier Proteins / immunology*
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Diphtheria Toxoid / administration & dosage
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Diphtheria Toxoid / immunology
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Drug Delivery Systems / methods
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Epitopes / immunology
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Immunity, Mucosal / immunology
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Immunoglobulin A / blood
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Immunoglobulin A / immunology
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Immunoglobulin G / blood
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Immunoglobulin G / immunology
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Immunotherapy, Active / methods*
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Lipids / administration & dosage*
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Lipids / chemistry
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Lipids / immunology
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Mice
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Molecular Sequence Data
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Peptide Fragments / chemistry
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Peptide Fragments / immunology*
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Streptococcal Infections / immunology
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Streptococcal Infections / prevention & control
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Streptococcal Vaccines / administration & dosage*
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Streptococcal Vaccines / immunology
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Streptococcus pyogenes / immunology
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Vaccines, Subunit / administration & dosage*
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Vaccines, Subunit / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Bacterial
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Antigens, Bacterial
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Bacterial Outer Membrane Proteins
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Carrier Proteins
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Diphtheria Toxoid
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Epitopes
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Immunoglobulin A
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Immunoglobulin G
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Lipids
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Peptide Fragments
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Streptococcal Vaccines
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Vaccines, Subunit
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streptococcal M protein