title: Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine.
abstract: Cervical cancer results from cervical infection by human papillomaviruses (HPV), especially HPV16. Previous studies have shown that intramuscular vaccination of women with an HPV16 virus-like particle (VLP) vaccine induced a strong IgG response and protected against genital HPV16 infection. However, an alternative route of administration that avoids parenteral injection while inducing mucosal immunity might facilitate vaccine implementation in some settings, and partially overcome the substantial variation in HPV16 antibodies at the cervix seen in ovulating women. In this study, women were vaccinated with escalating doses of HPV16L1 VLPs via nasal nebulisation, bronchial aerosolisation, or a combination of intramuscular and aerosol vaccination. The alternative routes of vaccination were well tolerated and many of the volunteers who received aerosol vaccinations exhibited serum antibody titers that were comparable to those induced by intramuscular vaccination. A mucosal immune response was induced by aerosol vaccination as demonstrated by the induction of anti-HPV16 VLP IgA secreting cells in PBMC and SIgA in secretions. Our data suggest that aerosol administration of HPV VLPs may represent a potential alternative to parenteral injection.
authors.affiliation: Department of Gynecology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland. dnardell@hospvd.ch
authors.forename: Denise
authors.initials: D
authors.lastname: Nardelli-Haefliger
authors.forename: Floriana
authors.initials: F
authors.lastname: Lurati
authors.forename: Daniel
authors.initials: D
authors.lastname: Wirthner
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: Françoise
authors.initials: F
authors.lastname: Ponci
authors.forename: Pierre
authors.initials: P
authors.lastname: De Grandi
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007273:Injections, Intramuscular; D008875:Middle Aged; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D020545:Respiratory Mucosa / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000336:Aerosols; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines