Review Article | Published:

Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule

Nature Reviews Microbiology volume 7, pages 393400 (2009) | Download Citation

  • A Corrigendum to this article was published on 15 July 2009

Abstract

Ebola virus infection is a highly lethal disease for which there are no effective therapeutic or preventive treatments. Several vaccines have provided immune protection in laboratory animals, but because outbreaks occur unpredictably and sporadically, vaccine efficacy cannot be proven in human trials, which is required for traditional regulatory approval. The Food and Drug Administration has introduced the 'animal rule', to allow laboratory animal data to be used to show efficacy when human trials are not logistically feasible. In this Review, we describe immune correlates of vaccine protection against Ebola virus in animals. This research provides a basis for bridging the gap from basic research to human vaccine responses in support of the licensing of vaccines through the animal rule.

Key points

  • Ebola is a rare but deadly disease caused by a filovirus for which no treatment or vaccine is available. Vaccine development for such diseases is hampered by the inability to test vaccines in volunteers or a target population.

  • The Food and Drug Administration (FDA) has instituted the 'animal rule' to allow approval of vaccines and drugs that cannot be tested in humans based on immune correlates in animal models.

  • In the case of Ebola, the relevant animal models are non-human primates and mice.

  • For Ebola, immune correlates consist of immunoglobulin G responses, although other factors, such as T cells, are also likely to be important in a successful immune response.

  • Vaccine candidates for Ebola vaccine include the glycoprotein and nucleocapsid proteins.

  • Initial testing of Ebola vaccines has shown a protective effect in non-human primates and positive antibody titres in humans.

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Acknowledgements

The authors thank C. Asiedu for careful reading of the manuscript, A. Tislerics and D. Jeffers for help with manuscript preparation and M. Cichanowski and B. Hartman for assistance with the figures.

Author information

Affiliations

  1. Biodefense Research Section, 40 Convent Drive, MSC 3005, Bethesda, Maryland 20892, USA.

    • Nancy J. Sullivan
  2. Clinical Trials Core Laboratory and Viral Pathogenesis Laboratory, 40 Convent Drive, MSC 3005, Bethesda, Maryland 20892, USA.

    • Julie E. Martin
    •  & Barney S. Graham
  3. Virology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Drive, MSC 3005, Bethesda, Maryland 20892, USA.

    • Gary J. Nabel

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Competing interests

N.J.S. and G.J.N. have an intellectual property application related to this subject through the National Institutes of Health.

Corresponding author

Correspondence to Nancy J. Sullivan.

Glossary

Immune correlate

A specific immune response to a vaccine that is closely associated with protection against infection, disease or some other defined end point.

Good Laboratory Practice

A set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived.

Good Clinical Practice

An ethical and scientific quality standard for designing, conducting, recording and reporting trials that involves the participation of humans.

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DOI

https://doi.org/10.1038/nrmicro2129

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