Prevention and treatment of experimental herpes simplex virus encephalitis with human immune serum globulin

Pooled human immunoglobulin suitable for intravenous administration (IGIV) was evaluated in the prophylaxis and treatment of herpes simplex virus (HSV) type 1 encephalitis in a murine model. Four-week-old BALB/c mice received a single intraperitoneal injection of IGIV or saline 24 h before or up to 24 h after intranasal infection with 10(4.6) PFU of HSV type 1. Treatment with IGIV was protective against death, and the protective effects were dose and time dependent. Treatment with IGIV blocked the production of HSV antibody by infected mice and reduced the number of trigeminal ganglia containing latent virus. Removal of neutralizing antibody from the IGIV pool did not eliminate the protective effect, whereas F(ab)2 fragments of IGIV, which had virus-neutralizing activity that was identical to that of native IGIV, conferred no protection against death. Pooled human IGIV was effective for the prevention and treatment of HSV encephalitis in mice. Antibody-mediated protection required the Fc portion of the immunoglobulin molecule but did not require the direct neutralization of virus.