Characterization of host immune responses in Ebola virus infections

Abstract

Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.

Keywords::

• adaptive immunity
• antigenic subversion
• Ebola
• immunoevasion
• innate immunity
• long-term immunity
• secreted glycoprotein
• type I IFN

Financial & competing interests disclosure

This work was supported by the Public Health Agency of Canada (PHAC) and funded by a Canadian Safety and Security Program (CSSP) grant to GP Kobinger and X Qiu. G Wong is the recipient of a Doctoral Research Award from the Canadian Institute for Health Research (CIHR). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Ebola evades host innate responses by downregulation of type I IFN responses with viral protein 24 and viral protein 35, as well as steric shielding and epitope masking with GP.

• Ebola evades host humoural responses through antigenic subversion with sGP and prevention of dendritic cell maturation with viral protein 35.

• Innate immune responses important for survival from Ebola infection appear to be dependent on virus species.

• Antibody-mediated immunity is critical and predictive for protection from infection with Ebola.

• Long-term immunity is currently poorly defined but seroprevalence, in addition to IgG titers, decreases over time.

• What is the minimum level of antibody required for protection from reinfection with Ebola?

• Would combining GP-specific IgG with antibodies directed against other Ebola antigens improve efficacy?