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Published on: March 24, 2017
Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses
Alexander Bukreyev1, Michelle Meyer1, Bronwyn Gunn2
1University of Texas Medical Branch.
Abstract:
The first-ever recent Marburg virus (MARV) outbreak in Ghana, West Africa and Equatorial Guinea has refocused efforts towards the development of therapeutics since no vaccine or treatment has been approved. mRNA vaccines were proven successful in a pandemic-response to severe acute respiratory syndrome coronavirus-2, making it an appealing vaccine platform to target highly pathogenic emerging viruses. Here, 1-methyl-pseudouridine-modified mRNA vaccines formulated in lipid nanoparticles (LNP) were developed against MARV and the closely-related Ravn virus (RAVV), which were based on sequences of the glycoproteins (GP) of the two viruses. Vaccination of guinea pigs with both vaccines elicited robust binding and neutralizing antibodies and conferred complete protection against virus replication, disease and death. The study characterized antibody responses to identify disparities in the binding and functional profiles between the two viruses and regions in GP that are broadly reactive. For the first time, the glycan cap is highlighted as an immunoreactive site for marburgviruses, inducing both binding and neutralizing antibody responses that are dependent on the virus. Profiling the antibody responses against the two viruses provided an insight into how antigenic differences may affect the response towards conserved GP regions which would otherwise be predicted to be cross-reactive and has implications for the future design of broadly protective vaccines. The results support the use of mRNA-LNPs against pathogens of high consequence.
Insights
New mRNA vaccines protected guinea pigs against Marburg virus (MARV) and Ravn virus (RAVV). This research highlights the potential of mRNA-lipid nanoparticle (LNP) technology for developing effective vaccines against high-consequence pathogens.
Area of Science:
- Virology and Immunology
- Vaccine Development
- Emerging Infectious Diseases
Background:
- Recent Marburg virus (MARV) outbreaks underscore the urgent need for effective therapeutics and vaccines.
- Messenger RNA (mRNA) vaccine platforms demonstrated success against SARS-CoV-2, showing promise for other highly pathogenic viruses.
Purpose of the Study:
- To develop and evaluate 1-methyl-pseudouridine-modified mRNA vaccines formulated in lipid nanoparticles (LNP) against MARV and Ravn virus (RAVV).
- To characterize antibody responses and assess vaccine efficacy in conferring protection against MARV and RAVV.
Main Methods:
- Development of MARV and RAVV mRNA vaccines based on viral glycoprotein (GP) sequences, formulated in LNPs.
- Vaccination of guinea pigs with the developed mRNA-LNPs.
- Assessment of binding and neutralizing antibody responses, and evaluation of protection against viral challenge.
Main Results:
- Vaccination elicited robust binding and neutralizing antibodies against both MARV and RAVV.
- Complete protection against virus replication, disease, and death was observed in vaccinated guinea pigs.
- The glycan cap of the viral GP was identified as a key immunoreactive site, inducing virus-dependent antibody responses.
Conclusions:
- mRNA-LNP vaccines are effective in protecting against MARV and RAVV, demonstrating complete protection in a preclinical model.
- Understanding antigenic differences and antibody responses to specific GP regions is crucial for designing broadly protective vaccines.
- The findings support the use of mRNA-LNP technology for developing vaccines against high-consequence viral pathogens.
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