The Journal of infectious diseases1999; 179 Suppl 1; S224-S234; doi: 10.1086/514310

Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections.

Abstract: A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial effect. Pretreatment of monkeys delayed onset of viremia and delayed death several additional days. Interferon-alpha2b (2 x 10(7) IU/kg/day) had a similar effect in monkeys, delaying viremia and death by only several days. Effective treatment of Ebola infections may require a combination of drugs that inhibit viral replication in monocyte/macrophage-like cells while reversing the pathologic effects (e.g., coagulopathy) consequent to this replication.
Publication Date: 1999-02-13 PubMed ID: 9988188DOI: 10.1086/514310Google Scholar: Lookup
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  • Journal Article

Summary

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The research article evaluates the effectiveness of immune globulin and recombinant interferon-alpha2b in treating experimental Ebola virus infections. The study indicates that treatment may be more effective when initiated before the development of viremia, and effective treatment may require a combination of drugs.

Study Overview

The study evaluated the applicability of passive immunization as a strategy in the treatment of Ebola infections. Passive immunization basically involves the sharing of active immune components from one individual to another. A diverse set of species were used, ranging from BALB/c mice, guinea pigs (strain 13), to cynomolgus monkeys.

  • The researchers initiated the treatment with the injection of hyperimmune equine IgG. This is a type of immune globulin derived from horses that have been hyperimmunized (overactive immune response).
  • The timing of the treatment was varied, with some receiving it right on the day of virus inoculation (day 0), while others starting later.

Findings

  • The research found that treatment was completely successful in guinea pigs when started early before the development of viremia (presence of the virus in the bloodstream). However, there was no protective effect when the treatment started after viremia had occurred.
  • In contrast, mice only received incomplete protection even when the treatment started on day 0.
  • For monkeys receiving one dose of IgG on day 0, the onset of illness and viremia was delayed, but all treated animals eventually died. A second dose of IgG on day 5 showed no additional benefits.
  • Pretreating monkeys achieved slightly better results by further delaying viremia and death for a few days more.
  • In addition, the application of Interferon-alpha2b showed a similar effect in monkeys, delaying viremia and death by only a few days.

Conclusion

The study suggests that effective treatment of Ebola infections might call for more than just immune globulin or interferon. It might require a combination of drugs capable of inhibiting viral replication in certain white blood cells (monocytes/macrophage-like cells) and reversing the pathologic effects like blood clotting disorders (e.g., coagulopathy) that result from viral replication. Therefore, while passive immunization shows potential, its current effectiveness appears to be conditional on early administration and may need to be combined with other strategies for better results.

Cite This Article

APA
Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ. (1999). Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J Infect Dis, 179 Suppl 1, S224-S234. https://doi.org/10.1086/514310

Publication

ISSN: 0022-1899
NlmUniqueID: 0413675
Country: United States
Language: English
Volume: 179 Suppl 1
Pages: S224-S234

Researcher Affiliations

Jahrling, P B
  • United States Army Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. PBJ@Detrick.Army.Mil
Geisbert, T W
    Geisbert, J B
      Swearengen, J R
        Bray, M
          Jaax, N K
            Huggins, J W
              LeDuc, J W
                Peters, C J

                  MeSH Terms

                  • Animals
                  • Antibodies, Viral / blood
                  • Antibodies, Viral / therapeutic use
                  • Disease Models, Animal
                  • Ebolavirus / immunology
                  • Ebolavirus / isolation & purification
                  • Ebolavirus / ultrastructure
                  • Guinea Pigs
                  • Hemorrhagic Fever, Ebola / immunology
                  • Hemorrhagic Fever, Ebola / therapy
                  • Hemorrhagic Fever, Ebola / virology
                  • Horses
                  • Humans
                  • Immunization, Passive
                  • Immunoglobulin G / blood
                  • Immunoglobulin G / therapeutic use
                  • Interferon alpha-2
                  • Interferon-alpha / therapeutic use
                  • Lymph Nodes / immunology
                  • Lymph Nodes / virology
                  • Macaca fascicularis
                  • Mice
                  • Mice, Inbred BALB C
                  • Microscopy, Electron
                  • Recombinant Proteins
                  • Time Factors
                  • Viremia / immunology
                  • Viremia / therapy

                  Citations

                  This article has been cited 123 times.