title: A retro-inverso peptide analogue of influenza virus hemagglutinin B-cell epitope 91-108 induces a strong mucosal and systemic immune response and confers protection in mice after intranasal immunization.
abstract: In this study, a novel approach for the development of a peptide-based vaccine has been tested. We investigated the possibility of replacing an all-L amino acid peptide sequence corresponding to the protective B-cell epitope hemagglutinin (HA) 91-108 from influenza HA with a retro-inverso analogue encompassing this sequence. Retro-inverso peptides are composed of D-amino acids assembled in a reverse order from that of the parent L-sequence, thus maintaining the overall topology of the native sequence. This explains the observed antigenic cross-reactivity with anti-influenza virus antibodies. Mice immunized intranasally with the ovalbumin-conjugated retro-inverso analogue and cholera toxin as an adjuvant, produced strong systemic (serum IgG) and mucosal (lung IgA) antibody responses, and were protected against intranasal challenge with a lethal dose of influenza virus. The weight loss pattern in the protected group indicated that the vaccinated animals developed a disease of low severity resulting in a quick recovery. Furthermore, splenocytes of the immunized mice cultured in the presence of inactivated influenza virus, secreted high levels of IFN-gamma. The half-life of the retro-inverso analogue in the presence of lung homogenate proteases was at least 700 times greater than that of the parent L-peptide. These results demonstrate that peptidomimetic analogues with high resistance to proteolytic degradation are very effective immunogens when administered via the intranasal route, inducing protective immunity against a viral infection. This approach might be advantageous for vaccine development.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, P.O. Box 26, 76100, Rehovot, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yedidia
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Beignon
authors.forename: Charalambos D
authors.initials: CD
authors.lastname: Partidos
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Ruth
authors.initials: R
authors.lastname: Arnon
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D018985:Epitopes, B-Lymphocyte; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D010446:Peptide Fragments; D018074:Vaccines, Conjugate; D007371:Interferon-gamma