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. 1984 May;44(2):528–533. doi: 10.1128/iai.44.2.528-533.1984

Passive antibody therapy of Lassa fever in cynomolgus monkeys: importance of neutralizing antibody and Lassa virus strain.

P B Jahrling, C J Peters
PMCID: PMC263556  PMID: 6715049

Abstract

Lassa virus-infected cynomolgus monkeys were passively immunized with immune plasma of primate or human origin to gain insight into criteria for plasma selection and administration to human Lassa fever patients. Protective efficacy was correlated with neutralizing antibody concentrations, expressed as a log10 neutralization index (LNI). Convalescent Lassa-immune monkey plasma was titrated for protective efficacy in monkeys by intravenous inoculation with dilutions of plasma on the day of subcutaneous Lassa virus inoculation (day 0) and again on days 3 and 6. Monkeys that received undiluted plasma (LNI = 4.1) (1 ml/kg per treatment) survived a lethal viral dose, whereas those given a 1:3 dilution (LNI = 2.6) of this same plasma (1 ml/kg per treatment) died. Protection was restored when the volume of the 1:3 plasma dilution was increased to 3 ml/kg per treatment. Plasma diluted 1:9 or more (LNI = 1.5 or less) delayed onset and suppressed the magnitude of viremia but failed to confer protection at 3 ml/kg per treatment. Immunological enhancement, defined as increased viremia or accelerated death, did not occur following inadequate treatment. Human convalescent plasma also protected recipient monkeys; reductions in mortality and viremia were accurately predicted by the LNI of the plasma. Plasma of Liberian origin neutralized a Liberian Lassa strain more effectively than a Sierra Leone strain in vitro (LNI = 2.8 and 1.6, respectively) and protected monkeys more effectively against the Liberian strain. Geographic origin is thus a factor in the selection of optimal plasma for treatment of human Lassa fever, since geographically matched plasma is more likely to contain adequate LNI titers against homologous Lassa virus strains.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clayton A. J. Lassa immune serum. Bull World Health Organ. 1977;55(4):435–439. [PMC free article] [PubMed] [Google Scholar]
  2. Condie R. M., O'Reilly R. J. Prophylaxis of CMV infection in bone marrow transplant recipients by hyperimmune CMV gamma-globulin. Dev Biol Stand. 1982;52:501–513. [PubMed] [Google Scholar]
  3. Eddy G. A., Wagner F. S., Scott S. K., Mahlandt B. J. Protection of monkeys against Machupo virus by the passive administration of Bolivian haemorrhagic fever immunoglobulin (human origin). Bull World Health Organ. 1975;52(4-6):723–727. [PMC free article] [PubMed] [Google Scholar]
  4. Halstead S. B. Immune enhancement of viral infection. Prog Allergy. 1982;31:301–364. [PubMed] [Google Scholar]
  5. Jahrling P. B., Hesse R. A., Eddy G. A., Johnson K. M., Callis R. T., Stephen E. L. Lassa virus infection of rhesus monkeys: pathogenesis and treatment with ribavirin. J Infect Dis. 1980 May;141(5):580–589. doi: 10.1093/infdis/141.5.580. [DOI] [PubMed] [Google Scholar]
  6. Jahrling P. B., Peters C. J., Stephen E. L. Enhanced treatment of Lassa fever by immune plasma combined with ribavirin in cynomolgus monkeys. J Infect Dis. 1984 Mar;149(3):420–427. doi: 10.1093/infdis/149.3.420. [DOI] [PubMed] [Google Scholar]
  7. Jahrling P. B. Protection of Lassa virus-infected guinea pigs with Lassa-immune plasma of guinea pig, primate, and human origin. J Med Virol. 1983;12(2):93–102. doi: 10.1002/jmv.1890120203. [DOI] [PubMed] [Google Scholar]
  8. Jahrling P. B., Smith S., Hesse R. A., Rhoderick J. B. Pathogenesis of Lassa virus infection in guinea pigs. Infect Immun. 1982 Aug;37(2):771–778. doi: 10.1128/iai.37.2.771-778.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Keane E., Gilles H. M. Lassa fever in Panguma Hospital, Sierra Leone, 1973-6. Br Med J. 1977 May 28;1(6073):1399–1402. doi: 10.1136/bmj.1.6073.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kiley M. P., Lange J. V., Johnson K. M. Protection of rhesus monkeys from Lassa virus by immunisation with closely related Arenavirus. Lancet. 1979 Oct 6;2(8145):738–738. doi: 10.1016/s0140-6736(79)90659-7. [DOI] [PubMed] [Google Scholar]
  11. Layton L. L., Arimoto L., Lamanna C., Olson R., Sharp D. Immunochemical and physiological comparison of horse botulinal antitoxins. Jpn J Med Sci Biol. 1972 Oct;25(5):309–320. doi: 10.7883/yoken1952.25.309. [DOI] [PubMed] [Google Scholar]
  12. Leifer E., Gocke D. J., Bourne H. Lassa fever, a new virus disease of man from West Africa. II. Report of a laboratory-acquired infection treated with plasma from a person recently recovered from the disease. Am J Trop Med Hyg. 1970 Jul;19(4):677–679. doi: 10.4269/ajtmh.1970.19.677. [DOI] [PubMed] [Google Scholar]
  13. Maiztegui J. I., Fernandez N. J., de Damilano A. J. Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome. Lancet. 1979 Dec 8;2(8154):1216–1217. doi: 10.1016/s0140-6736(79)92335-3. [DOI] [PubMed] [Google Scholar]
  14. Monath T. P., Casals J. Diagnosis of Lassa fever and the isolation and management of patients. Bull World Health Organ. 1975;52(4-6):707–715. [PMC free article] [PubMed] [Google Scholar]
  15. Monath T. P., Maher M., Casals J., Kissling R. E., Cacciapuoti A. Lassa fever in the Eastern Province of Sierra Leone, 1970-1972. II. Clinical observations and virological studies on selected hospital cases. Am J Trop Med Hyg. 1974 Nov;23(6):1140–1149. doi: 10.4269/ajtmh.1974.23.1140. [DOI] [PubMed] [Google Scholar]
  16. White H. A. Lassa fever. A study of 23 hospital cases. Trans R Soc Trop Med Hyg. 1972;66(3):390–401. doi: 10.1016/0035-9203(72)90269-6. [DOI] [PubMed] [Google Scholar]
  17. Wulff H., Johnson K. M. Immunoglobulin M and G responses measured by immunofluorescence in patients with Lassa or Marburg virus infections. Bull World Health Organ. 1979;57(4):631–635. [PMC free article] [PubMed] [Google Scholar]

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