Protection of Lassa Virus-Infected Guinea Pigs with Lassa-Immune Plasma of Guinea Pig, Primate, and Human Origin
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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Lassa virus-immune plasma has been used to treat human Lassa fever patients however, criteria for plasma selection were based arbitrarily on available serologic tools and protective efficacy was never directly assessed. To test the validity of plasma therapy for Lassa virus infections in an animal model, and to develop biologically relevant criteria for selection of protective immune plasma, inbred, strain 13 guinea pigs were infected with a lethal dose of Lassa virus and treated with various Lassa-immune plasmas obtained from guinea pigs, primates, and convalescent human patients. Neutralizing antibody titers were determined in a virus dilution, plaque reduction test, and were expressed as a log plaque-forming units PFU neutralization index LNI. All guinea pigs treated with immune plasma 6 mlkgtreatment on days 0, 3, and 6 after virus inoculation were protected, provided the LNI exceeded 2.0. Plasmas obtained from donors in early convalescence 32-45 days had low titers of N-antibody LNI 2 and failed to confer protection, despite high titers of Lassa antibody measured in the indirect fluorescent antibody IFA test. Higher doses of marginally titered plasma conferred increased protection. The degree of protection and suppression of viremia was closely associated with LNI and not IFA titers. Administration of low-titered plasma did not result in immune enhancement. A high dose of human plasma from Liberia 12 mlkgtreatment was required to confer complete protection to guinea pigs infected with a virus strain from Sierra Leone LNI 1.6, while a lower dose 3 mlkgtreatment was sufficient for protection against a Liberian strain LNI 2.8, suggesting that a geographic matching of immune plasma and Lassa virus strain origin may increase treatment success. These studies support the concept of plasma therapy for Lassa infection and suggest that the plaque reduction neutralization test is more appropriate than the IFA test for predicting...
- Medicine and Medical Research