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230 Immunization Strategies to Augment Oral Vaccination with DNA and Viral Vectors Expressing HIV Envelope Glycoprotein
T. Naito*1, J. Gzyl1, E. Bolesta1, D. Kmieciak1, H. Pletcher2, and D. Kozbor1
1Temple Univ., Philadelphia, PA, USA and 2Univ. of Pennsylvania, Philadelphia, USA
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. We investigated the effect of an oral DNA-prime/rVV-boost vaccine regimen on the level of gp160-specific cellular and humoral responses. We demonstrated that DNA priming followed by a booster with rVV expressing gp160 (vPE16) significantly augmented env-specific immunity in systemic and mucosal tissues. Association of vPE16 with liposomes triggered the optimal cell-mediated immune (CMI) responses. In subsequent studies, we explored the association of liposomes with replication-attenuated modified vaccinia Ankara (MVA) expressing gp160 and ?-galactosidase (?-Gal) for protection from neutralizing antibodies. Using cationic liposomes with active polyethylene glycol groups grafted into a lipid membrane, we were able to achieve approximately 70% protection from neutralizing antibodies both in vitro and in vivo. The latter was determined by comparing the level of beta-Gal in the gut tissues 14 h after intragastric delivery of free or liposome-associated MVA to preimmunized BALB/c mice. The analysis of DiO-labeled liposome and DiI-labeled MVA by flow cytometry revealed the presence of viral particles complexed with liposomes. Preliminary studies demonstrated induction of env-specific CMI in preimmunized mice with the MVA-liposome complexes. Experiments are in progress to determine whether the MVA-liposome complexes are capable of inducing env-specific immune responses in mucosal and systemic tissues after multiple immunizations.
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