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Discovery of common marburgvirus protective epitopes in a BALB/c mouse model
Warren V Kalina1, Kelly L Warfield, Gene G Olinger
1Division of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Fort Detrick, Maryland, 21702, USA.
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.
Conclusion:
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.
Insights
Researchers identified Marburg virus (MARV) CD8+ T-cell epitopes in GP and NP proteins. These epitopes induce protective cytotoxic T-cell responses, crucial for combating MARV infection.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Marburg virus (MARV) causes lethal hemorrhagic fever with no available vaccines.
- Immune mechanisms for MARV protection are not fully understood, but T cells are implicated.
- This study aimed to map CD8+ T-cell epitopes in MARV-infected mice.
Purpose of the Study:
- To identify specific CD8+ T-cell epitopes within Marburg virus proteins.
- To evaluate the capacity of these epitopes to induce protective cellular immune responses.
- To establish tools for studying T-cell mediated immunity against MARV.
Main Methods:
- Infection of BALB/c mice with nonlethal MARV.
- Stimulation of splenocytes with overlapping MARV peptide pools.
- Identification of CD8+ T-cell epitopes using interferon-gamma and CD44 expression, followed by assessment of cytotoxic T-cell responses and protection against lethal MARV challenge.
Main Results:
- Discovery of CD8+ T-cell epitopes within MARV glycoprotein (GP) and nucleoprotein (NP).
- These epitopes elicited cytotoxic T-cell responses.
- Transfer of epitope-specific splenocytes conferred protection against lethal MARV challenge.
Conclusions:
- Specific MARV-epitope induction of cellular immunity is sufficient to combat infection.
- Identified CD8+ T-cell epitopes serve as valuable tools for dissecting cellular immune responses to MARV.
- This research advances understanding of T-cell mediated protection against Marburg virus.
