Ocular safety and efficacy of an HSV-1 gD vaccine during primary and latent infection.
One potential complication of systemic herpes simplex virus (HSV) vaccination is that subsequent ocular infection may lead to increased immunogenic corneal scarring. Therefore, V52, a genetically engineered vaccinia virus that expresses the HSV-1 glycoprotein gD, was tested for ocular safety and for protection against ocular challenge with a stromal-disease-producing strain (McKrae) of HSV-1. To maximize immune response, rabbits were vaccinated by a series of inoculations. V52-vaccinated rabbits developed significant HSV-1 neutralizing antibody titers; however, they were not as high as those induced by vaccination with live HSV-1 McKrae. One month after the final vaccination, all rabbits were challenged ocularly. Eyes were monitored for 35 days for epithelial keratitis, stromal keratitis, and iritis. In no case was epithelial keratitis, stromal keratitis, or iritis significantly exacerbated by vaccination. The gD V52 recombinant vaccine provided protection against HSV-1 induced epithelial keratitis (P = 0.02) and long-term stromal scarring (P = 0.04). There was no significant reduction in the incidence of trigeminal ganglionic latency in the vaccinated rabbits (P greater than 0.05). Thus, our results indicate that V52, a gD recombinant vaccine probably is safe with regard to corneal scarring, and may provide a small amount of protection against ocular HSV-1 infection. The amount of protection provided was less than that reported in mice and guinea pigs. This suggests that to provide high levels of ocular protection in rabbits (and probably in humans), HSV-1 vaccines may have to elicit a more vigorous immune response than that produced by normal HSV-1 infection.
Nesburn
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Ophthalmology Research, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Ghiasi
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H
Wechsler
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D000818:Animals; D007478:Iontophoresis; D007500:Iritis / Q000517:prevention & control; D007635:Keratitis, Dendritic / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D009500:Neutralization Tests; D011817:Rabbits; D018139:Simplexvirus / Q000254:growth & development; D014612:Vaccines / Q000633:toxicity*; D014614:Vaccines, Synthetic / Q000633:toxicity*; D014616:Vaccinia virus; D014759:Viral Envelope Proteins / Q000633:toxicity*; D014765:Viral Vaccines / Q000633:toxicity*; D014775:Virus Activation / Q000187:drug effects
D014612:Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1