Immunization strategies to augment oral vaccination with DNA and viral vectors expressing HIV envelope glycoprotein.
Induction of mucosal immunity to the human immunodeficiency virus (HIV) envelope (env; gp160) glycoprotein has been demonstrated with orally administered recombinant vaccinia virus (rVV) vectors and poly(DL-lactide-co-glycolide) (PLG)-encapsulated plasmid DNA expressing gp160. In this study, we investigated the effect of an oral DNA-prime/rVV-boost vaccine regimen in conjunction with adjuvants on the level of gp160-specific cellular and humoral responses in BALB/c mice. We demonstrated that DNA priming followed by a booster with rVV expressing gp160 (vPE16) significantly augmented env-specific immunity in systemic and mucosal tissues of the immunized mice. Association of vPE16 with liposomes and coadministration of liposome-associated beta-glucan lentinan or IL-2/Ig-encoded plasmid DNA-encapsulated in PLG microparticles triggered the optimal cell-mediated immune (CMI) responses. Lentinan was found to increase env-specific type 1 cytokine production and cytotoxic T-lymphocyte (CTL) activities but had no effect on humoral responses. On the other hand, IL-2/Ig-mediated increases in both type 1 and 2 activities were associated with higher levels of env-specific CTL and antibody responses. Results of these studies demonstrated the effectiveness of oral vaccines with DNA and rVV vectors in conjunction with immunomodulators in inducing specific immune responses in systemic and mucosal tissues.
Wierzbicki
Andrzej
A
Center for Neurovirology, MCP Hahnemann University, Philadelphia, PA 19102, USA.
Kiszka
Irena
I
Kaneko
Hiroshi
H
Kmieciak
Dariusz
D
Wasik
Thomas J
TJ
Gzyl
Jaroslaw
J
Kaneko
Yutaro
Y
Kozbor
Danuta
D
D016915:AIDS Vaccines / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D015483:HIV Antibodies / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000235:genetics; D019344:Lactic Acid / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D016915:AIDS Vaccines; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007376:Interleukin-2; D011108:Polymers; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma