Oral DNA vaccination promotes mucosal and systemic immune responses to HIV envelope glycoprotein.
In this report, we described induction of HIV envelope (env)-specific systemic and mucosal immune responses by oral vaccination of BALB/c mice with env-encoded plasmid DNA encapsulated in poly(dl-lactide-co-glycolide) (PLG) microparticles. We demonstrated that intragastric administration of the encapsulated plasmid DNA resulted in transduced expression of the env glycoprotein in the intestinal epithelium. Mice immunized orally exhibited env-specific type 1 and cytotoxic T lymphocyte (CTL) responses in spleen and the inductive (Peyer's patches) and effector (lamina propria) mucosal tissues of gut. Oral administration of PLG-encapsulated plasmid DNA encoding gp160 also induced env-specific serum antibodies, and an increased level of IgA directed to gp160 was detected in fecal washes of the immunized mice. In contrast, intramuscular (i.m.) administration of naked or PLG-encapsulated DNA vaccine induced only systemic cellular and humoral responses to the env glycoprotein. Using an HIV env-expressing recombinant vaccinia viral intrarectal murine challenge system, we observed higher resistance to mucosal viral transmission in mice immunized orally than in animals injected i.m. with PLG-encapsulated plasmid DNA encoding gp160. Results of these studies demonstrate the feasibility of using orally delivered PLG microparticles containing plasmid DNA-encoded HIV gp160 for induction of env-specific systemic and mucosal immune responses and protection against recombinant HIV env vaccinia virus challenge.
Kaneko
H
H
Department of Microbiology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania, 19107-6799, USA.
Bednarek
I
I
Wierzbicki
A
A
Kiszka
I
I
Dmochowski
M
M
Wasik
T J
TJ
Kaneko
Y
Y
Kozbor
D
D
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004064:Digestive System / Q000276:immunology / Q000821:virology; D005243:Feces / Q000821:virology; D005260:Female; D015870:Gene Expression; D015752:Genes, env; D015483:HIV Antibodies / Q000096:biosynthesis*; D019302:HIV Envelope Protein gp160 / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D017931:DNA Primers; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007070:Immunoglobulin A; D012333:RNA, Messenger; D012367:RNA, Viral; D019444:Vaccines, DNA; D007371:Interferon-gamma