Neutralizing antibodies inhibit axonal spread of herpes simplex virus type1 to epidermal cells in vitro

The ability of antibodies to interfere with anterograde transmission of her pes simplex virus (HSV) from neuronal axons to the epidermis was investigat ed in an in vitro model consisting of human fetal dorsal root ganglia inner vating autologous skin explants in a dual-chamber tissue culture system. Th e number and size of viral cytopathic plaques in epidermal cells after axon al transmission from HSV type 1 (HSV-1)-infected dorsal root ganglionic neu rons were significantly reduced by addition to the outer chamber of neutral izing polyclonal human sera to HSV-1, of a human recombinant monoclonal gro up Ib antibody to glycoprotein D (gD), and of rabbit sera to HSV-1 gB and g o but not by rabbit anti-gE or anti-gG. A similar pattern of inhibition of direct infection of epidermal cells by these antibodies was observed. High concentrations of the monoclonal anti-go reduced transmission by 90%, Rabbi t anti-gB was not taken up into neurons, and human anti-go did not influenc e spread of HSV in the dorsal root ganglia or axonal transport of HSV antig ens when applied to individual dissociated neurons. These results suggest t hat anti-go and -gB antibodies interfere with axonal spread of HSV-1, possi bly by neutralizing RSV during transmission across an intercellular gap bet ween axonal termini and epidermal cells, and thus contribute to control of HSV spread and shedding. Therefore, selected human monoclonal antibodies to protective epitopes might even be effective in preventing epidermis-to-neu ron transmission during primary HSV infection, especially neonatal infectio n.