Determinants of Protection by Human Immune Globulin against Experimental Herpes Neonatorum 1

Abstract

There is no established prophylaxis of Herpes neonatorum. In experimental, newborn animals protection can be achieved by sufficient passive antibody given shortly after infection. Animal model data was sought to estimate a realistic and practical dose of human immune globulin for prophylaxis of newborn humans at risk. We used a neonatal mouse model and type II herpes simplex virus (HSV) to evaluate factors which govern the efficiency of antibody prophylaxis. Antibodies prepared in mice, rabbits, or man were equally protective. Timing experiments showed that these antibodies gradually lose their protective effect when administered more than 12 hr after infection. The first dose of multiple doses of antibody is the most crucial for protection. Intraperitoneal or subcutaneous injections of human immune globulin were equally effective. About 65 units of human anti-HSV antibody in 1-g newborn mice was the minimum dose which resulted in maximum protection. Comparison of this minimum protective dose with levels of neutralizing antibody in commercial immune globulin indicated that approximately 100 ml would be needed to achieve similar protective serum antibody levels in man. Six percent of potential blood donors were determined to have sufficient HSV antibody titers (≤1000 units) to prepare hyperimmune globulin at least 10 times more potent than commercially available immune globulin. Only 10 ml or less of such hyperimmune globulin is estimated to be protective. This reduced volume of hyperimmune globulin is easily injected into the loose subcutaneous tissue in the backs of newborn children.