Improved protection from primary ocular HSV-1 infection and establishment of latency using multigenic DNA vaccines.
OBJECTIVE
To compare the effectiveness of immunization with "naked" DNA corresponding to the genes encoding five HSV-1 glycoproteins, gB, gC, gD, gE, and gI (5gP DNA), with immunization with the five glycoproteins (5gP protein). Also, to compare immunization of 5gP protein in Montanide ISA 720 (SEPPIC, Paris, France), an adjuvant recently approved for use in humans, with immunization of 5gP protein in Freund's adjuvant.


METHODS
BALB/c mice were vaccinated with 5gP DNA or 5gP protein emulsified in ISA 720 or Freund's adjuvant. Neutralizing antibody titers were determined by plaque-reduction assays. IL-2, -4, and -12 and IFN-gamma levels were determined by ELISA after in vitro stimulation of spleen cells. After ocular challenge with 2 x 10(5) plaque-forming units [pfu] per eye of HSV-1 strain McKrae, virus replication in the eye, survival, blepharitis, corneal scarring, and latency were determined.


RESULTS
Neutralizing antibody titers (approximately 1:800-1:1200), corneal scarring (trace) and survival (100%) were similar for all vaccine groups, including 5gP DNA. Compared with 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 720 appeared more effective than Freund's against ocular virus replication and eye disease. The 5gP DNA-vaccinated mice had less blepharitis and latency than any other group and had the highest levels of IL-12 and IFN-gamma. All vaccine groups had similar levels of IL-2.


CONCLUSIONS
The 5gP DNA vaccine appeared to be more effective than the corresponding protein subunit vaccine, regardless of adjuvant. Emulsification of the 5gP protein in ISA 720 appeared to be more effective than emulsification in Freund's adjuvant.
Osorio
Yanira
Y
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA.
Cohen
Jacob
J
Ghiasi
Homayon
H
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001762:Blepharitis / Q000401:mortality / Q000517:prevention & control / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000627:therapeutic use; D022301:Herpes Simplex Virus Vaccines / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007635:Keratitis, Dendritic / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D008353:Mannitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009829:Oleic Acids / Q000627:therapeutic use; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D017735:Virus Latency; D014779:Virus Replication / Q000502:physiology
D000914:Antibodies, Viral; D016207:Cytokines; D022301:Herpes Simplex Virus Vaccines; D009829:Oleic Acids; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C001681:mannide monooleate; D008353:Mannitol; D005620:Freund's Adjuvant