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Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection.
Title | Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Shlapobersky, M, Marshak, JO, Dong, L, Huang, M-L, Wei, Q, Chu, A, Rolland, A, Sullivan, S, Koelle, DM |
Journal | J Gen Virol |
Volume | 93 |
Issue | Pt 6 |
Pagination | 1305-15 |
Date Published | 2012 Jun |
ISSN | 1465-2099 |
Keywords | Adjuvants, Immunologic, Animals, Antibodies, Viral, Female, Herpes Genitalis, Herpesvirus 2, Human, Mice, Mice, Inbred BALB C, Phosphatidylethanolamines, Plasmids, Vaccines, DNA, Viral Envelope Proteins, Viral Vaccines |
Abstract | The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL) and secreted (S) gD2 forms. A 0.1 µg pDNA dose was tested to distinguish treatment conditions for survival and a 100 µg pDNA dose was tested to distinguish treatment conditions for reduction in vaginal and latent HSV-2 copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500 LD(50) inoculum. At this high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80 % survival compared with no survival for FL gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 µg pDNA dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA alone. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2 pDNA alone were positive for HSV-2 viral genomes. These results show the potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2 vaccine. |
DOI | 10.1099/vir.0.040055-0 |
Alternate Journal | J. Gen. Virol. |
PubMed ID | 22398318 |