title: Antipeptide antibody responses following intranasal immunization: effectiveness of mucosal adjuvants.
abstract: Toxicity is a major factor limiting the development and use of potent adjuvants for human mucosally delivered vaccines. Novel adjuvant formulations have recently become available, and in the present study two have been used for intranasal immunization with a synthetic peptide immunogen (MAP-M2). This peptide represents a multiple antigenic peptide containing multiple copies of a mimotope M2, a peptide mimic of a conformational epitope of the fusion protein of measles virus. MAP-M2 was administered intranasally to experimental animals together with synthetic oligodeoxynucleotides containing unmethylated CpG motifs with or without a mutant of wild-type enterotoxin of Escherichia coli (LTR72). The combination of the mutant toxin LTR72 and the CpG repeats, codelivered with a peptide immunogen, induced both local and systemic peptide- and pathogen-specific humoral and cellular immune responses comparable to those obtained after intranasal immunization with the wild-type toxin LT. In addition, this combination of adjuvants induced a predominantly immunoglobulin G2a antibody response. If both the LTR72 and CpG adjuvants are shown to be safe for use in humans, this particular combination would appear to have potential as an adjuvant for mucosally delivered vaccines in humans.
authors.affiliation: The Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
authors.forename: W
authors.initials: W
authors.lastname: Olszewska
authors.forename: C D
authors.initials: CD
authors.lastname: Partidos
authors.forename: M W
authors.initials: MW
authors.lastname: Steward
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001427:Bacterial Toxins / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D029968:Escherichia coli Proteins; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007371:Interferon-gamma / Q000032:analysis; D008213:Lymphocyte Activation; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D015226:Dinucleoside Phosphates; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D007371:Interferon-gamma; D009838:Oligodeoxyribonucleotides; D014760:Viral Fusion Proteins; C015772:CpG dinucleotide; C027538:heat-labile enterotoxin, E coli