title: Antibody, cytokine and cytotoxic T lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles.
abstract: We evaluated antibody, cytokine (IFN-gamma, IL-5, TNF-alpha), and cytotoxic T lymphocyte (CTL) responses in chimpanzees immunized with monovalent or quadrivalent (HPV-6, -11, -16, -18) L1 virus-like particle (VLP) vaccines administered i.m. on aluminum hydroxyphosphate (alum) at weeks 0, 8 and 24. Maximum serum antibody titers to type-specific, neutralizing, conformational epitopes on HPV-11 or -16 L1 VLPs were detected by radioimmunoassay (RIA) four weeks after the second and third immunizations. HPV-11 and -16 neutralizing antibodies were also detected at similar time points with an Human papillomaviruses (HPV) neutralization assay using pseudovirions. Depending on the VLP type used for immunization, HPV type-specific cytokine responses were most frequently seen four weeks after the second or third immunizations and between weeks 44-52. Transient HPV-16 L1-specific CTL activity was observed only between weeks 16-24 in 3 of 22 (13.6%) chimpanzees immunized with HPV-16 L1 VLPs. These findings provide evidence that immunization with multivalent L1 VLPs on alum can evoke both neutralizing antibodies and Th1 and Th2 cytokine responses to several HPV types; however, induction of CTLs is infrequent.
authors.affiliation: Department of Virus and Cell Biology, Merck Research Laboratories, Merck and Co., Inc., WP16-101, Sumneytown Pike, West Point, PA 19486, USA. tom_palker@merck.com
authors.forename: T J
authors.initials: TJ
authors.lastname: Palker
authors.forename: J M
authors.initials: JM
authors.lastname: Monteiro
authors.forename: M M
authors.initials: MM
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Kakareka
authors.forename: J F
authors.initials: JF
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: Cook
authors.forename: J G
authors.initials: JG
authors.lastname: Joyce
authors.forename: K U
authors.initials: KU
authors.lastname: Jansen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007115:Immunization Schedule; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D002679:Pan troglodytes; D027383:Papillomaviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014771:Virion / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines