title: Human immunodeficiency virus type 1 gag-specific mucosal immunity after oral immunization with papillomavirus pseudoviruses encoding gag.
abstract: Mucosal surfaces are the primary portals for human immunodeficiency virus (HIV) transmission. Because systemic immunization, in general, does not induce effective mucosal immune responses, a mucosal HIV vaccine is urgently needed. For this study, we developed papillomavirus pseudoviruses that express HIV-1 Gag. The pseudoviruses are synthetic, nonreplicating viruses, yet they can produce antigens for a long time in the immune system. Here we show that oral immunization of mice by the use of papillomavirus pseudoviruses encoding Gag generated mucosal and systemic Gag-specific cytotoxic T lymphocytes that effectively lysed Gag-expressing target cells. Furthermore, the pseudoviruses generated Gag-specific gamma interferon-producing T cells and serum immunoglobulin G (IgG) and mucosal IgA. In contrast, oral immunization with plasmid DNA encoding HIV-1 Gag did not induce specific immune responses. Importantly, oral immunization with the pseudoviruses induced Gag-specific memory cytotoxic T lymphocytes and protected mice against a rectal mucosal challenge with a recombinant vaccinia virus expressing HIV-1 Gag. Thus, papillomavirus pseudoviruses encoding Gag are a promising mucosal vaccine against AIDS.
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago Medical Center, 2160 South First Ave., Maywood, IL 60153, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Raja
authors.initials: R
authors.lastname: Fayad
authors.forename: Xilin
authors.initials: X
authors.lastname: Wang
authors.forename: Daniel
authors.initials: D
authors.lastname: Quinn
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010053:Ovary / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000472:pathogenicity
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015683:Gene Products, gag; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D007371:Interferon-gamma