Virus-like particles (VLPs) prepared from chikungunya virus structural proteins
Inventors
Nabel, Gary J. • Akahata, Wataru • Rao, Srinivas
Assignees
US Department of Health and Human Services
Publication Number
US-9353353-B2
Publication Date
2016-05-31
Expiration Date
2029-11-24
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Abstract
The invention features compositions and methods for the prevention or treatment of one or more strains of Chikungunya virus, as well as other alphavirus-mediated diseases.
Core Innovation
The invention features compositions and methods for the prevention or treatment of one or more strains of Chikungunya virus, as well as other alphavirus-mediated diseases. It provides virus-like particles (VLPs) containing one or more Chikungunya virus structural polypeptides, including capsid and envelope proteins E3, E2, 6K, and E1, and immunogenic compositions containing these VLPs for inducing immune responses against Chikungunya virus infection.
The problem addressed by the invention arises from the spread and severity of Chikungunya virus (CHIKV) infections, which cause rash, high fever, and severe arthritis possibly persisting for years. Since re-emerging in 2004, CHIKV has infected millions across Africa, Europe, and Asia, with no existing vaccines or antiviral therapies, posing a serious public health threat. There are three genotypes with varying similarity and divergence, and urgent therapeutic and prophylactic measures are needed to treat or prevent Chikungunya viral disease.
Accordingly, the invention provides virus-like particles composed of CHIKV structural polypeptides, isolated polynucleotides encoding these VLPs, expression vectors, recombinant host cells expressing one or more CHIKV structural proteins capable of self-assembling into VLPs, and immunogenic compositions (including vaccines) containing these VLPs. The invention also involves methods of inducing immune responses by administering these compositions or nucleic acids, methods of producing VLPs in cells, and methods for treating or preventing Chikungunya infection by immunization with VLPs or DNA vaccines encoding CHIKV proteins.
Claims Coverage
The patent contains one independent claim relating to virus-like particles containing Chikungunya virus structural proteins and their use in immunogenic compositions.
Virus-like particle containing Chikungunya virus strain 37997 structural polypeptides
A virus-like particle (VLP) comprising one or more Chikungunya virus structural polypeptides from strain 37997, specifically lacking genetic information encoding the VLP proteins.
Structural polypeptides comprising capsid and envelope proteins
The structural polypeptides included in the VLP are selected from capsid (C) and envelope proteins E3, E2, 6K, and E1.
VLP comprising complete envelope protein set
The VLP may comprise envelope proteins E3, E2, 6K, and E1.
VLP comprising polyprotein
The VLP may comprise a polyprotein containing C-E3-E2-6K-E1.
Immunogenic composition containing VLP
An immunogenic composition containing an effective amount of the virus-like particle to induce an immune response.
Adjuvanted immunogenic composition
The immunogenic composition optionally includes an adjuvant that is an immunostimulating agent, such as Ribi, aluminum salts, muramyl peptides, bacterial cell wall components, or saponin adjuvants.
Cross-reactive antibody induction
The VLP induces antibodies that neutralize both homologous and heterologous strains of Chikungunya virus.
The claims cover virus-like particles derived from Chikungunya virus strain 37997 structural proteins, particularly capsid and envelope proteins, their assembly into VLPs devoid of genetic information, immunogenic compositions containing these particles with or without adjuvants, and the ability to induce cross-strain neutralizing antibodies.
Stated Advantages
VLP immunization elicits potent neutralizing antibody responses that are 100-fold higher than DNA vaccines.
VLPs induce cross-strain neutralizing antibodies against homologous and heterologous Chikungunya virus strains.
Immunization with VLPs protects non-human primates against viremia and inflammatory consequences after Chikungunya virus challenge.
Passive transfer of antibodies generated by VLP immunization confers protection against lethal Chikungunya virus challenge in mice.
VLP vaccines are safer and potentially more effective than previous live attenuated or inactivated vaccine candidates.
Documented Applications
Prevention or treatment of Chikungunya virus infection in subjects, including humans.
Induction of protective immunity against multiple strains of Chikungunya virus through vaccination with VLPs or DNA vaccines encoding structural proteins.
Use of immunogenic compositions for therapeutic or prophylactic administration to induce immune responses to prevent or ameliorate Chikungunya viral disease and its symptoms, such as arthritis.
Methods for producing VLPs by expressing one or more CHIKV structural proteins in suitable host cells.
Screening methods for identifying inhibitors of Chikungunya virus entry into eukaryotic cells using pseudotyped lentiviral vectors and reporter genes.
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