Human immunodeficiency virus type 1 gag-specific mucosal immunity after oral immunization with papillomavirus pseudoviruses encoding gag.
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.
Zhang
Hongtao
H
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago Medical Center, 2160 South First Ave., Maywood, IL 60153, USA.
Fayad
Raja
R
Wang
Xilin
X
Quinn
Daniel
D
Qiao
Liang
L
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
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015683:Gene Products, gag; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D007371:Interferon-gamma