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Bivalent Junin & Machupo experimental vaccine based on alphavirus RNA replicon vector
Dylan M Johnson1, Jenny D Jokinen2, Min Wang2
1Department of Microbiology and Immunology, School of Medicine, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, NIH Regional Bio-containment Laboratory, University of Louisville, KY, USA.
Vaccine
|March 1, 2020
Summary
A new vaccine using virus-like-particle vectors (VLPVs) expresses glycoproteins from Junin virus (JUNV) and Machupo virus (MACV). This VLPV vaccine is safe, immunogenic, and protects against lethal hemorrhagic fevers in animal models.
Area of Science:
- Virology
- Vaccinology
- Infectious Diseases
Background:
- Junin virus (JUNV) and Machupo virus (MACV) cause severe hemorrhagic fevers and are WHO-listed threats.
- Current live-attenuated JUNV vaccines have limitations, including restricted use in certain populations and potential US approval hurdles.
- Existing vaccines do not effectively neutralize MACV due to variations in viral glycoproteins.
Purpose of the Study:
- To develop a novel vaccine strategy against JUNV and MACV using alphavirus RNA replicon vector technology.
- To create replication-restricted virus-like-particle vectors (VLPVs) expressing glycoprotein precursors (GPC) of both JUNV and MACV.
- To assess the safety and immunogenicity of the developed VLPVs and their protective efficacy against lethal arenaviral challenge.
Main Methods:
- Utilized Venezuelan equine encephalitis virus (VEEV) TC-83 based alphavirus RNA replicon vector technology.
- Generated VLPVs engineered to express GPC of both JUNV and MACV.
- Evaluated VLPV safety and immunogenicity in guinea pig models, followed by challenge with pathogenic JUNV and MACV strains.
Main Results:
- JV&MV VLPVs demonstrated safety and induced robust humoral immune responses in immunized guinea pigs.
- Humoral responses correlated with complete protection against lethal challenge with both JUNV (Romero strain) and MACV (Carvallo strain).
- The VLPV approach successfully addressed limitations of existing vaccines, offering broad protection against related arenaviruses.
Conclusions:
- Alphavirus VLPV technology provides a promising platform for developing safe and effective vaccines against JUNV and MACV.
- This novel vaccine strategy offers potential for broader application, including in populations not suitable for current vaccines.
- The study highlights the potential of VLPVs to induce cross-protective immunity against related hemorrhagic fever viruses.
