Passive immunity for arbovirus infection: I. Artificially Induced Prophylaxis in man and mouse for Japanese (B) encephalitis

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  • 1 Department of Epidemiology and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
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In an attempt to determine quantitatively the amount of specific human immune serum or human gamma globulin needed to protect man against infection by an arbovirus a series of experiments was carried out in mice and in men. As a model, Japanese (B) encephalitis was employed. Consideration was given to buth post- and pre-exposure types of usage. Related literature on arbovirus passive prophylaxis was reviewed. In the mouse, using hyperimmune mouse serum given subcutaneously and challenge 1 day later with virus by a “peripheral” (intraperitoneal) route, results agreed with those previously published by Sabin for western equine encephalitis virus in that a serum antibody level just detectable by the intracerebral mouse neutralization test offered significant protection. However, the antibody appeared to be released very slowly into the blood stream. The half-life calculated for the antibody under these circumstances was about 3.5 days. In man, a gamma globulin prepared from hyperimmunized Japanese with a log10 neutralization index (LNI) of 4.1 at a 1:10 dilution was given to three normal volunteers, then to five laboratory workers following potential accidental exposure from inoculation of highly virulent, high titered low passage virus. This was given intramuscularly in a volume of less than 20 ml, calculated to be between 0.07 and 0.2 ml/kg body weight. In all but the lowest dosage LNTs of 2.1 to 3.4 were detected in the recipients' serum, usually peaking several days to 1 or 2 weeks after administration and a detectable titer persisted for from 1 to 5 weeks. No disease occurred and none had developed antibody 5 to 12 weeks later. Titers of gamma globulin prepared from plasma or placentas from nationals of several Asian countries, where the disease is endemic, are presented. One high-titered human serum was given directly to four volunteers in dosages of 5 to 20 ml and serum antibody levels were followed. Methods of performing neutralization tests to titer antibody of gamma globulin without “accessory substance(s),” and of fresh or frozen human immune serum are compared and discussed. Recommendations are made regarding practical usage of both substances for post-exposure prophylaxis, and a basis for tentative conclusions is given in respect to pre-exposure (seasonal) prophylaxis.

Author Notes

Present address: Virology Branch, Arbovirology Section, Center for Disease Control, Building No. 5, Atlanta, Georgia 30333.