Monovalent Virus-Like Particle Vaccine Protects Guinea Pigs and Nonhuman Primates Against Infection with Multiple Marburg Viruses
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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Virus-like particle VLP-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. Expression of the glycoprotein and VP40 matrix protein from Lake Victoria marburgvirus MARV results in spontaneous production of VLPs in mammalian cells. Guinea pigs vaccinated with marburgvirus mVLPs or inactivated MARV iMARV develop homologous humoral and T cell responses and are completely protected from a lethal homologous MARV challenge. To determine whether the mVLPs, based on the Musoke aka Lake Victoria isolate of MARV, could broadly protect against diverse isolates of MARV, guinea pigs were vaccinated with mVLPs or inactivated MARV-Musoke and challenged with MARV-Musoke, -Ravn, or -Ci67. Prior to challenge, the mVLP- and iMARV-vaccinated guinea pigs had high levels of homologous MARV-Musoke and heterologous MARV-Ravn and -Ci67 antibodies. The Musoke-based mVLPs and iMARV vaccines provided complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn, or -Ci67. Guinea pigs vaccinated with RIBI adjuvant alone and infected with guinea pig-adapted MARV- Musoke, -Ravn, or -Ci67 had histopathologic findings similar to those seen in the nonhuman NHP model for MARV virus infection. Based on the strong protection observed in guinea pigs, we next vaccinated cynomolgus macaques with Musoke-based mVLPs and showed the VLP-vaccinated monkeys were broadly protected against three isolates of MARV Musoke, Ravn, and Ci67. Thus, Musoke marburgvirus-based VLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates.
- Medicine and Medical Research