title: Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers.
abstract: The sublingual route has been proposed as a needle-free option to induce systemic and mucosal immune protection against viral infections. In a translational study of systemic and mucosal humoral immune responses to sublingual or systemically administered viral antigens, eighteen healthy female volunteers aged 19-31 years received three immunizations with a quadravalent Human Papilloma Virus vaccine at 0, 4 and 16 weeks as sublingual drops (SL, n = 12) or intramuscular injection (IM, n = 6). IM antigen delivery induced or boosted HPV-specific serum IgG and pseudovirus-neutralizing antibodies, HPV-specific cervical and vaginal IgG, and elicited circulating IgG and IgA antibody secreting cells. SL antigens induced ~38-fold lower serum and ~2-fold lower cervical/vaginal IgG than IM delivery, and induced or boosted serum virus neutralizing antibody in only 3/12 subjects. Neither route reproducibly induced HPV-specific mucosal IgA. Alternative delivery systems and adjuvants will be required to enhance and evaluate immune responses following sublingual immunization in humans.
  
  
  BACKGROUND
  ClinicalTrials.govNCT00949572.
authors.affiliation: Infectious Diseases, St George's - University of London, London, United Kingdom.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Huo
authors.forename: Sara L
authors.initials: SL
authors.lastname: Bissett
authors.forename: Raphaela
authors.initials: R
authors.lastname: Giemza
authors.forename: Simon
authors.initials: S
authors.lastname: Beddows
authors.forename: Clarissa
authors.initials: C
authors.lastname: Oeser
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D052685:Alphapapillomavirus / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage*; D036022:Capsid Proteins / Q000276:immunology; D002584:Cervix Uteri / Q000276:immunology; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D052140:Human papillomavirus 11 / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D052163:Human papillomavirus 6 / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007273:Injections, Intramuscular; D009856:Oncogene Proteins, Viral / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D014621:Vagina / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; C094776:L1 protein, Human papillomavirus type 11; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; C091560:L1 protein, Human papillomavirus type 6; C063317:L1 protein, Human papillomavirus type 16; C480565:L1 protein, Human papillomavirus type 18