Discovery of common marburgvirus protective epitopes in a BALB/c mouse model.
BACKGROUND
Marburg virus (MARV) causes acute hemorrhagic fever that is often lethal, and no licensed vaccines are available for preventing this deadly viral infection. The immune mechanisms for protection against MARV are poorly understood, but previous studies suggest that both antibodies and T cells are required. In our study, we infected BALB/c mice with plaque-purified, nonlethal MARV and used overlapping peptides to map H2d-restricted CD8+ T-cell epitopes.


METHODS
Splenocytes from mice infected with nonlethal MARV were harvested and stimulated with multiple overlapping 15-mer peptide pools, and reactive CD8+ T cells were evaluated for antigen specificity by measuring upregulation of CD44 and interferon-gamma expression. After confirming positive reactivity to specific 15-mer peptides, we used extrapolated 9-mer epitopes to evaluate the induction of cytotoxic T-cell responses and protection from lethal MARV challenge in BALB/c mice.


RESULTS
We discovered a CD8+ T-cell epitope within both the MARV glycoprotein (GP) and nucleoprotein (NP) that triggered cytotoxic T-cell responses. These responses were also protective when epitope-specific splenocytes were transferred into naïve animals.


CONCLUSIONS
Epitope mapping of MARV GP, NP, and VP40 provides the first evidence that specific MARV-epitope induction of cellular immune responses is sufficient to combat infection. Establishment of CD8+ T-cell epitopes that are reactive to MARV proteins provides an important research tool for dissecting the significance of cellular immune responses in BALB/c mice infected with MARV.
Kalina
Warren V
WV
Division of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Fort Detrick, Maryland, 21702, USA.
Warfield
Kelly L
KL
Olinger
Gene G
GG
Bavari
Sina
S
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008379:Marburg Virus Disease / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D029024:Marburgvirus / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000737:chemistry / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D009698:Nucleoproteins; D014759:Viral Envelope Proteins