Induction of a Mucosal Immune Response to the Streptococcal M Protein by Intramuscular Administration of a PADRE‐ASREAK Peptide

Abstract

In a previous study, it was shown that an intramuscular administration of amino acid PADRE-ELDKWA sequence induced a mucosal immune response to a conserved epitope of human immunodeficiency virus in mice. In the same model, here it is shown that this method can be used with a selected peptide from the M protein of group A streptococci. The PADRE-ASREAK sequence was injected in mice by the intramuscular route. Antibodies against M protein were detected in extracts of mucosal tissues and in serum. The repertoire isotypes of serum immunoglobulin G (IgG) and mucosal IgA and IgG antibodies varied, according to the dose of injected peptide. The highest mucosal IgA antibody response was obtained with 0.01 mg of antigen per injection, whereas the systemic IgG antibody response increased with 10 mg of antigen. Mucosal antibody production against streptococci was confirmed by immunofluorescence analysis. These results provide evidence that this novel approach of mucosal vaccination may be of advantage for bacterial systems and suggest a new field of investigation based on synthetic peptide analogues.

Th-Cytotoxic T-Lymphocyte Chimeric Epitopes Extended by N ε -Palmitoyl Lysines Induce Herpes Simplex Virus Type 1-Specific Effector CD8 + Tc 1 Responses and Protect against Ocular Infection

“…ϩ Th determinant that binds to most murine and human MHC class II molecules (5,26,32,39). To assess the influence of the number of lipid units on the induction of protective CD8 ϩ T cells, the resulting chimeric peptide backbone, solely composed of both Th and CTL epitopes, was extended by N-terminal addition of one, two, or three palmitic acid moieties.…”

Enhanced immunogenicity of the modified GP5 of porcine reproductive and respiratory syndrome virus

“…In our modified GP5, the inserted heterologous sequence, which was used to display the neutralizing epitope and to eliminate the decoy effect of the non-neutralizing epitope, consisted of a PADRE. This universal T-helper cell epitope has been used as the adjuvant for various epitopes (including B cell, CTL and carbohydrate epitopes), and was shown to be efficient in enhancing the immunogenicity of these epitopes in DNA vaccines and subunit vaccines [20,23,[31][32][33][34]. The immunoadjuvant effect of the PADRE made it unclear whether the enhancement of immune response was due to the complete uncovering of the neutralizing epitope of GP5 or the direct effects of the PADRE itself.…”

Heteropentameric Cholera Toxin B Subunit Chimeric Molecules Genetically Fused to a Vaccine Antigen Induce Systemic and Mucosal Immune Responses: a Potential New Strategy To Target Recombinant Vaccine Antigens to Mucosal Immune Systems

“…Having a similar mechanism of protein secretion for yeast and mammalian cells, heteropentameric constructs may have advantages over homopentamers or holotoxin-like molecules; their secretory nature may increase cellular uptake of the fusion chimera by adjacent cells or by the professional antigen-presenting cells for increased major histocompatibility complex class I and/or class II presentation to elicit enhanced humoral as well as cellular immune responses (possibly including mucosal responses) (7,28).…”