Treatment method utilizing chikungunya virus (CHIKV) virus-like particles (VLPS) comprising the C, E2 and E1 structural proteins
Inventors
Nabel, Gary J. • Akahata, Wataru • Rao, Srinivas
Assignees
US Department of Health and Human Services
Publication Number
US-11369674-B2
Publication Date
2022-06-28
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 (CHIKV), as well as other alphavirus-mediated diseases. It provides virus-like particles (VLPs) containing one or more of the Chikungunya virus structural polypeptides, including capsid (C) and envelope proteins E3, E2, 6K, and E1. The invention also includes isolated polynucleotides encoding these VLPs, expression vectors comprising these polynucleotides, cells containing these vectors, immunogenic compositions containing VLPs or expression vectors, and vaccines containing VLPs, structural polypeptides, or polynucleotides encoding these proteins.
The problem being solved arises from the public health threat posed by the Chikungunya virus, a mosquito-borne alphavirus causing severe arthritis, rash, and high fever with millions infected since its re-emergence in 2004. The disease severity, evolutionary spread into new geographic areas, and absence of effective vaccines or antiviral therapies create an urgent need for therapeutic and prophylactic methods to prevent or treat CHIKV infection and related alphavirus diseases.
The invention addresses this need by producing VLPs that mimic the structure and antigens of CHIKV, capable of inducing protective immunity against both homologous and heterologous strains of the virus. These VLPs elicit neutralizing antibodies and protective immune responses in animal models, including non-human primates. Additionally, methods cover production of VLPs through expression of viral structural proteins in suitable host cells, formulation into vaccines with adjuvants, and immunization protocols including prime-boost regimens. The invention facilitates safer and effective immunization strategies for CHIKV and related alphavirus infections.
Claims Coverage
The patent includes one independent claim focused on a method for treating or preventing Chikungunya virus infection using virus-like particles comprising specific structural proteins of the CHIKV strain 37997. The main inventive features relate to the composition and use of these VLPs and their protein components.
Use of virus-like particles for CHIKV treatment or prevention
A method of treating or preventing Chikungunya virus infection comprising administering to a subject a virus-like particle comprising CHIKV strain 37997 structural proteins, where the VLP does not carry genetic information encoding the proteins.
Specific structural proteins included in the VLP
The VLP includes at least CHIKV capsid (C) protein, CHIKV E2 protein, and CHIKV E1 protein, with optional inclusion of CHIKV E3 and 6K proteins.
Variations in the envelope protein composition of VLPs
Embodiments where the VLP comprises envelope proteins E3, E2, 6K, and E1; or envelope proteins E1 and E2 plus capsid; or envelope proteins E1 and E2 alone.
Prevention of CHIKV infection and at-risk subject treatment
The method comprises preventing CHIKV infection by administering the VLP to subjects at risk of infection.
The claims cover methods utilizing non-genetic-information carrying VLPs comprising selected CHIKV structural proteins to treat or prevent CHIKV infection, emphasizing specific combinations of capsid and envelope proteins and their use in susceptible subjects.
Stated Advantages
Induces potent neutralizing antibody responses against homologous and heterologous CHIKV strains.
Protects non-human primates against viremia and inflammatory consequences of CHIKV infection.
Safe and effective immunization strategy showing cross-strain reactivity and high antibody titers.
Passive transfer of antibodies induced by the VLPs protects against lethal CHIKV challenge in mice.
Documented Applications
Use as an immunogenic composition or vaccine to induce protective immunity against CHIKV infection in humans and non-human primates.
Treatment or prevention of CHIKV infection by administering VLPs comprising CHIKV structural proteins.
Methods of producing VLPs by expression of structural proteins in host cells for vaccine preparation.
Use of passive transfer of neutralizing antibodies generated against the VLPs for protective treatment.
In vitro assays for identifying inhibitors of CHIKV viral entry using pseudotyped lentiviral vectors containing CHIKV envelope proteins.
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