Analysis of the role of antibody-dependent cellular cytotoxic antibody activity in murine neonatal herpes simplex virus infection with antibodies to synthetic peptides of glycoprotein D and monoclonal antibodies to glycoprotein B.

Abstract

The role of antibody in neonatal herpes simplex virus (HSV) infection remains controversial. A battery of well-characterized monoclonal antibodies to HSV glycoprotein B (gB), and polyclonal antibodies against synthetic peptides of predicted epitopes of HSV glycoprotein D (gD) were used to determine in vitro functional activity and association with protection against lethal infection in a murine model of neonatal HSV disease. Antiviral neutralization activity of HSV was not associated with antibody-dependent cellular cytotoxicity (ADCC) activity to HSV-infected cells in vitro. In a model of high dose challenge (104 PFU), protection was not afforded by any antibody alone, but was by antibody plus human mononuclear cells, and highly associated with ADCC functional activity (P < 0.001). In a low dose challenge model, neutralizing activity of antibody alone was associated with protection in vivo (P < 0.001). Of the nine neutralizing epitopes of gD in vitro, eight were predicted surface regions. Four of the five epitopic sites of gD (2-21, 267-276, 288-297, and 303-312) that were determined to be important targets of ADCC and in vivo protection were also predicted to be surface regions. The only exception was the antiserum to region 52-61 which was predicted to be buried and also showed these activities. ADCC as well as neutralizing antibody activity are important in protection against neonatal HSV infection. (J. Clin. Invest. 1990. 86:273-278.)

Concomitant Helper Response Rescues Otherwise Low Avidity CD8+ Memory CTLs to Become Efficient Effectors In Vivo

“…In fact, we have observed that mice coimmunized with ICP27 peptide ϩ gD 4 -23 are markedly more resistant to HSV challenge than are ICP27 peptide-immunized mice. However, the recipients of gD 4 -23 also generate CD4 ϩ and Ab response to HSV, which as shown previously also protect against challenge (29). The issue of assessing the in vivo significance of high avidity CTL requires evaluation in circumstances which avoid such complications.…”

A human monoclonal antibody against varicella-zoster virus glycoprotein III

“…Monoclonal antibodies (MAbs), which consist of a pure antibody protein, have high antibody titres and some show very potent antiviral activity (Grose et al, 1983;Forghani et al, 1984;Keller et al, 1984;Kohl et al, 1990). All these MAbs are of rodent origin and are recognized as foreign substances by the human immune system (Khazaeli et al, 1988).…”

Vaccine-Elicited Antibodies Mediate Antibody-Dependent Cellular Cytotoxicity Correlated with Significantly Reduced Acute Viremia in Rhesus Macaques Challenged with SIVmac251

“…F cR-bearing cells armed with Abs can kill virus-infected cells by Ab-dependent cellular cytotoxicity (ADCC), 3 an immune mechanism known to occur in vitro and in vivo (1)(2)(3). Passive transfer of Abs with in vitro ADCC activity against HSVinfected cells, for example, can protect complement-deficient mice against lethal challenge with HSV, despite the inability of the Abs to neutralize the virus (4).…”