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Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection
Kelly L Warfield1, Dana L Swenson, Diane L Negley
1United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011, USA. kelly.warfield@det.amedd.army.mil
Abstract:
Ongoing outbreaks of filoviruses in Africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. We previously reported the generation of virus-like particles (VLPs) for the filoviruses, Marburg (MARV) and Ebola (EBOV) virus, and that vaccinating mice with Ebola VLPs (eVLPs) results in complete survival from a lethal EBOV challenge. The objective of this study was to determine the efficacy of Marburg VLPs (mVLPs) as a potential vaccine against lethal MARV infection in a guinea pig model. Guinea pigs vaccinated with mVLPs or inactivated MARV developed MARV-specific antibody titers, as tested by ELISA or plaque-reduction and neutralization assays and were completely protected from a MARV challenge over 2000 LD50. While eVLP vaccination induced high EBOV-specific antibody responses, it did not cross-protect against MARV challenge in guinea pigs. Vaccination with mVLP or eVLP induced proliferative responses in vitro only upon re-exposure to the homologous antigen and this recall proliferative response was dependent on the presence of CD4+ T cells. Taken together with our previous work, these findings suggest that VLPs are a promising vaccine candidate for the deadly filovirus infections.
Insights
Marburg virus-like particles (mVLPs) demonstrate significant potential as a vaccine, offering complete protection against lethal Marburg virus infection in guinea pigs. This study highlights VLPs as a promising strategy against deadly filovirus diseases.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Filovirus outbreaks in Africa and bioterrorism concerns necessitate effective vaccines.
- Previous work generated Ebola virus-like particles (VLPs) that protected mice against Ebola virus challenge.
- Efficacy of Marburg VLPs (mVLPs) against Marburg virus (MARV) required evaluation.
Purpose of the Study:
- To determine the efficacy of Marburg VLPs (mVLPs) as a vaccine against lethal Marburg virus infection.
- To assess cross-protection capabilities of Ebola VLPs (eVLPs) against Marburg virus.
Main Methods:
- Guinea pigs were vaccinated with mVLPs or inactivated Marburg virus.
- MARV-specific antibody titers were measured using ELISA and plaque-reduction neutralization assays.
- Animals were challenged with a lethal dose of Marburg virus (over 2000 LD50).
- T cell proliferation assays were conducted post-vaccination.
Main Results:
- Vaccination with mVLPs or inactivated MARV induced MARV-specific antibodies.
- All vaccinated guinea pigs were completely protected from lethal MARV challenge.
- Ebola VLPs (eVLPs) did not provide cross-protection against MARV challenge.
- T cell recall responses were homologous and CD4+ T cell-dependent.
Conclusions:
- Marburg VLPs (mVLPs) are a promising vaccine candidate against Marburg virus.
- VLPs offer a potential strategy for preventing deadly filovirus infections.
- Homologous antigen specificity and CD4+ T cell involvement are key to VLP-induced immunity.
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