Evaluation of genetic immunization adjuvants to improve the effectiveness of a human immunodeficiency virus type 2 (HIV-2) envelope DNA vaccine.
In an effort to develop a more effective genetic immunization strategy for HIV, we developed an HIV-2 env DNA vaccine and evaluated three adjuvant formulations. The gp140 gene from HIV-2(UC2 )was synthesized using mammalian codons and cloned into a plasmid vector that expresses eukaryotic genes at high levels. We found that after three immunizations in mice, a novel cationic liposome formulation (Vaxfectin) was superior at inducing systemic and mucosal antibody responses compared to a naked DNA, a controlled release device (an Alzet minipump) and polysaccharide microparticles made from chitosan (P = 0.027). Vaxfectin also induced higher levels of systemic antibodies for each isotype and IgG subclass as well as levels of HIV-2-specific mucosal IgA (P = 0.034). When different routes of immunization were used with the Vaxfectin formulation, gp140-specific systemic antibody responses were highest by the intradermal route, mucosal antibody responses were highest by the intramuscular route, while the intranasal route was the least effective. These results suggest that this cationic liposome formulation is an important adjuvant to improve the effectiveness of genetic immunization strategies for AIDS, and that multiple routes of immunization should be employed for optimal efficacy for HIV vaccine candidates.
Locher
Christopher P
CP
Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, California, USA. christopher.locher@maxygen.com
Witt
Stephanie A
SA
Ashlock
Brittany M
BM
Levy
Jay A
JA
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005069:Evaluation Studies as Topic; D015686:Gene Products, env / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051379:Mice; D010714:Phosphatidylethanolamines; D011498:Protein Precursors / Q000235:genetics* / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics*; D054299:env Gene Products, Human Immunodeficiency Virus
D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D010714:Phosphatidylethanolamines; D011498:Protein Precursors; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C066315:gp140 envelope protein, Human immunodeficiency virus 2; C460866:vaxfectin