title: The comparison of the effect of LTR72 and MF59 adjuvants on mouse humoral response to intranasal immunisation with human papillomavirus type 6b (HPV-6b) virus-like particles.
abstract: Infections with genital human papillomaviruses (HPV) are likely to be neutralised more efficiently if a mucosal immune response can be elicited at the viral entry site. Local IgA antibodies are highly induced when antigens are co-administered with mucosal adjuvants, such as cholera toxin (CT) and Escherichia coli heat labile enterotoxin (LT) which, however, are not expected to have wide application because of their pronounced toxicity. We have immunised mice intranasally with HPV-6b virus-like particles (VLPs) and a genetically modified LT-derived molecule with only residual toxicity, LTR72, and compared the humoral responses with those obtained following systemic immunisation with VLPs and the MF59 adjuvant. Titration of anti-HPV antibodies in sera and vaginal secretions established that LTR72 was able to elicit higher serum and mucosal IgA titers, in addition to IgG serum levels, comparable to those obtained by parenteral immunisation. These results confirm the potential of toxin-derived adjuvants and extend their use in combination with HPV antigens.
authors.affiliation: Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Greer
authors.forename: R
authors.initials: R
authors.lastname: Petracca
authors.forename: D T
authors.initials: DT
authors.lastname: Buonamassa
authors.forename: A
authors.initials: A
authors.lastname: Di Tommaso
authors.forename: B
authors.initials: B
authors.lastname: Gervase
authors.forename: R L
authors.initials: RL
authors.lastname: Reeve
authors.forename: M
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: G
authors.initials: G
authors.lastname: Van Nest
authors.forename: M T
authors.initials: MT
authors.lastname: De Magistris
authors.forename: G
authors.initials: G
authors.lastname: Bensi
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001427:Bacterial Toxins / Q000494:pharmacology*; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D005260:Female; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D027383:Papillomaviridae / Q000276:immunology*; D011136:Polysorbates / Q000494:pharmacology*; D013185:Squalene / Q000494:pharmacology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C089950:MF59 oil emulsion; D011136:Polysorbates; D014765:Viral Vaccines; D013185:Squalene; C027538:heat-labile enterotoxin, E coli