Methods for the induction of immune responses in a subject compromising administering 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-10369208-B2
Publication Date
2019-08-06
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, particularly through the use of virus-like particles (VLPs) prepared from structural proteins of CHIKV.
The problem being solved is the lack of vaccines or anti-viral therapies against CHIKV, an alphavirus causing severe arthritis and widespread infection in Africa, Europe, and Asia since its re-emergence in 2004. The spread of the virus, its serious disease severity, and absence of effective treatment or prevention options create an urgent need for anti-viral therapies and vaccine development.
The invention provides VLPs containing one or more CHIKV structural polypeptides, including capsid and envelope proteins (E3, E2, 6K, E1), isolated polynucleotides encoding these VLPs, expression vectors, and cells containing such vectors for producing the VLPs. Immunogenic compositions and vaccines comprising effective amounts of these VLPs or polynucleotides are provided. Methods for inducing immune responses and for treating or preventing CHIKV infection involve administering the immunogenic compositions or vaccines to subjects. The VLPs closely resemble native virus morphology and induce potent neutralizing antibody responses that protect against homologous and heterologous strains, as demonstrated in animal models, including non-human primates and mice.
Claims Coverage
The patent claims focus on methods of inducing immune responses against Chikungunya virus using compositions containing virus-like particles (VLPs) comprising structural proteins from CHIKV strain 37997, as well as the use of adjuvants and the elicitation of neutralizing antibodies.
Method for inducing an immune response using VLPs from CHIKV strain 37997
A method for inducing an immune response against CHIKV in a subject by administering a composition comprising a virus-like particle (VLP) comprising one or more structural proteins from CHIKV strain 37997, wherein the VLP lacks genetic information encoding the VLP proteins.
Use of one or more CHIKV structural proteins in VLPs
The VLPs comprise one or more structural proteins selected from CHIKV capsid (C) protein, E3 protein, E2 protein, 6K protein, and E1 protein.
VLPs comprising CHIKV envelope proteins E3, E2, 6K and E1
The VLPs include CHIKV envelope proteins specifically comprising E3, E2, 6K, and E1.
Use of adjuvants to enhance immunogenicity
The compositions comprising the VLPs can include an adjuvant to improve immune response.
Adjuvant selection
The adjuvant can be selected from Ribi, aluminum salts, muramyl peptides, bacterial cell wall components, and saponin adjuvants.
Immune response eliciting antibodies against diverse CHIKV strains
The immune response induced by the VLP composition comprises antibodies against both homologous and heterologous strains of Chikungunya virus.
The claims encompass methods to induce immune responses using VLP compositions comprising CHIKV structural proteins from strain 37997, formulations with immunostimulatory adjuvants, and elicitation of broadly neutralizing antibodies against multiple CHIKV strains.
Stated Advantages
VLPs induce a more potent neutralizing antibody response to CHIKV than DNA vaccines.
Immunization protects against viremia and the inflammatory consequences of CHIKV infection.
Humoral immune responses induced by CHIKV VLPs confer protection against CHIKV infection.
VLPs are highly immunogenic and elicit higher titer neutralizing antibody responses than protein subunit vaccines.
Documented Applications
Prevention or treatment of one or more strains of Chikungunya virus infection in humans or mammals.
Use of VLPs for inducing immune responses against CHIKV in subjects.
Preparation of vaccines and immunogenic compositions containing VLPs or DNA vaccines encoding CHIKV structural proteins.
Identification of inhibitors of CHIKV viral entry into eukaryotic cells using assays involving CHIKV receptor-expressing cells and reporter gene expression.
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