Protection from Ebola virus mediated by cytotoxic T lymphocytes specific for the viral nucleoprotein.
Cytotoxic T lymphocytes (CTLs) are proposed to be critical for protection from intracellular pathogens such as Ebola virus. However, there have been no demonstrations that protection against Ebola virus is mediated by Ebola virus-specific CTLs. Here, we report that C57BL/6 mice vaccinated with Venezuelan equine encephalitis virus replicons encoding the Ebola virus nucleoprotein (NP) survived lethal challenge with Ebola virus. Vaccination induced both antibodies to the NP and a major histocompatibility complex class I-restricted CTL response to an 11-amino-acid sequence in the amino-terminal portion of the Ebola virus NP. Passive transfer of polyclonal NP-specific antiserum did not protect recipient mice. In contrast, adoptive transfer of CTLs specific for the Ebola virus NP protected unvaccinated mice from lethal Ebola virus challenge. The protective CTLs were CD8(+), restricted to the D(b) class I molecule, and recognized an epitope within amino acids 43 to 53 (VYQVNNLEEIC) in the Ebola virus NP. The demonstration that CTLs can prevent lethal Ebola virus infection affects vaccine development in that protective cellular immune responses may be required for optimal protection from Ebola virus.
Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA.
J A
JA
Wilson
M K
MK
Hart
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D029043:Ebolavirus / Q000276:immunology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D007116:Immunization, Passive; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000276:immunology*; D012093:Replicon / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D019590:Nucleocapsid Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C113190:nucleocapsid protein, Ebola virus