Induction of humoral and CD8+ T cell responses are required for protection against lethal Ebola virus infection.
Ebola virus (EBOV)-like particles (eVLP), composed of the EBOV glycoprotein and matrix viral protein (VP)40 with a lipid membrane, are a highly efficacious method of immunization against EBOV infection. The exact requirements for immunity against EBOV infection are poorly defined at this time. The goal of this work was to determine the requirements for EBOV immunity following eVLP vaccination. Vaccination of BALB/c or C57BL/6 mice with eVLPs in conjunction with QS-21 adjuvant resulted in mixed IgG subclass responses, a Th1-like memory cytokine response, and protection from lethal EBOV challenge. Further, this vaccination schedule led to the generation of both CD4(+) and CD8(+) IFN-gamma(+) T cells recognizing specific peptides within glycoprotein and VP40. The transfer of both serum and splenocytes, but not serum or splenocytes alone, from eVLP-vaccinated mice conferred protection against lethal EBOV infection in these studies. B cells were required for eVLP-mediated immunity to EBOV because B cell-deficient mice vaccinated with eVLPs were not protected from lethal EBOV challenge. We also found that CD8(+), but not CD4(+), T cells are absolutely required for eVLP-mediated protection against EBOV infection. Further, eVLP-induced protective mechanisms were perforin-independent, but IFN-gamma-dependent. Taken together, both EBOV-specific humoral and cytotoxic CD8(+) T cell responses are critical to mediate protection against filoviruses following eVLP vaccination.
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
Kelly L
KL
Warfield
Gene
G
Olinger
Emily M
EM
Deal
Dana L
DL
Swenson
Michael
M
Bailey
Diane L
DL
Negley
Mary Kate
MK
Hart
Sina
S
Bavari
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D029043:Ebolavirus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000401:mortality* / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D012503:Saponins / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D014771:Virion / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D012503:Saponins; C080981:VP40 protein, virus; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; C113189:envelope glycoprotein, Ebola virus; C078785:saponin QA-21V1; D007371:Interferon-gamma