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H Ghiasi, Y Osorio, AB Nesburn, J Cohen, SL Wechsler; A Naked Dna Vaccine Using A New High Level Expression Vector Is More Efficacious Against Ocular Hsv-1 Infection Than The Corresponding Subunit (protein) Vaccine . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3852.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Compare the efficacy of immunization with "naked" DNA corresponding to the genes for HSV-1 glycoproteins gB, gC, gD, gE, and gI (5gP DNA) using the novel high expression plasmid pVR1055 (Vical, Inc, San Diego) with that of a corresponding 5gP protein (subunit) vaccine. Also, compare the effectiveness of the adjuvants Montanide ISA 51 (Seppic, France) and Montanide ISA 720 that have recently been approved for use in humans, with Freund's adjuvant, as regards immunization with our 5gP protein vaccine. Methods: BALB/c mice were vaccinated with 5gP DNA, or 5gP protein using either ISA 51, ISA 720, or Freund's as adjuvant. Neutralizing antibody titers were determined by plaque reduction assays. IL-2, IL-4, IL-12, and IFN-gamma levels were determined by ELISA following in vitro stimulation of spleen cells. Following ocular challenge with lethal dose of HSV-1 strain McKrae, virus replication in the eye, survival, blepharitis, and corneal scarring were determined. Results: Neutralizing antibody titers (approximately 1:800 to 1:1200), corneal scarring (trace), and survival (100%) were similar for all vaccine groups, including 5gP DNA. Compared to the other vaccine groups, the 5gP DNA group had less ocular virus replication as judged both by maximum virus titer and time of viral clearance. ISA 51 and Freund's produced similar protection against ocular virus replication. Interestingly ISA 720 appeared more efficacious than Freund's against ocular virus replication and eye disease. The 5gP DNA vaccinated mice had less blepharitis then any other group and had the highest levels of IL-12 and IFN-gamma. All vaccine groups had similar levels of IL-2. Conclusion: (1)When used as adjuvant for the 5gP protein vaccine, ISA 720, which is safe and already approved for human use, appeared to be more efficacious than Freund's adjuvant. (2)The 5gP DNA vaccine using the new pVR1055 plasmid vector appeared to be more efficacious than the corresponding protein subunit vaccine, regardless of adjuvant.
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