Enhanced protection against HSV lethal challenges in mice by immunization with a combined HSV-1 glycoprotein B:H:L gene DNAs

The effectiveness of a cocktailed HSV-1 three-glycoprotein B, H, and L gene vaccine in comparison to individual glycoprotein gene vaccines was studied with regard to protecting against the HSV-1 infection. Three glycoprotein gene recombinant DNA vaccines, which produced the corresponding glycoproteins in Vero cells, were constructed using a CMV promoter. The cocktailed DNA vaccines were prepared by combining all three genes. The titers of neurtalizing antibody following the immunization of the five vaccines were KOS(1/1024) > B:H:L = B(1/512) > H:L(1/64) > H(1/16) genes. The mice, which were immunized with L gene alone failed to induce enough neutralizing antibody. The CTL activity was rated as KOS (95%) > B:H:L (80%) > B(60%) > H:L(50%) > H (35%) gene vaccines at an E:T ratio of 50:1. The H gene alone or L gene vaccine alone induced little CTL activity. The protection rates of the DNA-vaccinated mice against the lethal intraperitoneal (i.p.) or i.m challenges were shown as KOS > B:H:L > B > H:L > H gene vaccines, and the protection activity depended on the lethal dosage of the challenging virus, which are inversely proportional to each other. Compared with the mice, which were vaccinated with individual DNA vaccines, the mice, which were vaccinated with the cocktailed three-gene vaccine, were shown to be better protected against the lethal challenging doses. It can be concluded that vaccination with the cocktailed three gene vaccines is more effective in protecting mice from the viral challenge and the protection rate varies inversely with the amount of lethal challenging dose used, although all DNA vaccines failed to block the latent infection in sensory nerves. (C) 2002 Elsevier Science B.V. All rights reserved.