Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses
| Autor: | Sadie S. Coberley, D. A. Alves, Sina Bavari, Tom Larsen, Dana L. Swenson, Kelly L. Warfield |
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| Rok vydání: | 2008 |
| Předmět: |
Virosomes
Guinea Pigs Molecular Sequence Data Immunology Heterologous Viral Plaque Assay Antibodies Viral medicine.disease_cause Marburg virus VP40 Virus-like particle Immunity Drug Discovery medicine Animals Marburg Virus Disease Amino Acid Sequence Viremia Antigens Viral Pharmacology Viral matrix protein Ebola virus biology Animal Structures Viral Vaccines Survival Analysis Virology Macaca fascicularis Marburgvirus Vaccines Inactivated biology.protein Molecular Medicine Antibody Sequence Alignment |
| Zdroj: | Expert Review of Vaccines. 7:417-429 |
| ISSN: | 1744-8395 1476-0584 |
| DOI: | 10.1586/14760584.7.4.417 |
| Popis: | 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 Marburg virus VLPs (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 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 iMARV-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 primate model for MARV 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).Musoke mVLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates. |
| Databáze: | OpenAIRE |
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