Antibody-dependent enhancement of HSV-1 infection by anti-gK sera

We previously reported that vaccination of BALB/c mice with the baculovirus expressed HSV-1 glycoprotein K (gK) or passive transfer of gK purified IgG to naive BALB/c mice causes severe exacerbation of HSV-1 induced corneal s carring following ocular challenge. In addition, a productive chronic infec tion, rather than a latent infection, is found in most trigeminal ganglia. These phenomena are accompanied by a very high T(H)1 + T(H)2 response in th e eve (Ghiasi, H., Cai, S., Nesburn, A.B., Wechsler, S.L., 1996. Vaccinatio n with herpes simplex virus type 1 glycoprotein K impairs clearance of viru s from the trigeminal ganglia resulting in chronic infection. Virology 224, 330-333; Ghiasi, ii., Cai, S., Slanina, S., Nesburn, A.B., Wechsler, S.L., 1997. Nonneutralizing antibody against the glycoprotein K of herpes simple x virus type-1 exacerbates herpes simpler; virus type-1-induced corneal sca rring in various virus-mouse strain combinations. Invest. Ophthalmol. Vis. Sci. 38, 1213-1221; Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn , A.B., Wechsler, S.L., 1999. Vaccination with different HSV-1 glycoprotein s induces different patterns of ocular cytokine responses following HSV-1 c hallenge of vaccinated mice. Vaccine 17, 2576-2582). In the studies reporte d here, we investigated the hypothesis that anti-gK serum produces antibody -dependent enhancement (ADE) of ocular HSV-1 infection. We found that gK va ccinated mice had significantly higher HSV-1 titers in their eyes than go o l mock-vaccinated mice and that anti-gK sera enhanced HSV-1 infection in th e macrophage cell line U937. In addition, passive transfer of anti-gK sera to naive mice 24 h prior to ocular HSV-1 challenge also increased viral rep lication. These results were consistent with ADE of HSV-1 by sera to gK. Th is suggests that the severely exacerbated corneal disease seen following HS V-1 ocular challenge of gK vaccinated mice is a result of ADE. The ability of gK saa to cause harmful ADE may impact HSV-I vaccine development. (C) 20 00 Elsevier Science B.V. All rights reserved.