Rotavirus antigens
Inventors
Dormitzer, Philip R. • Harrison, Stephen C. • Greenberg, Harry B. • Yoder, Joshua
Assignees
Boston Childrens Hospital • National Institutes of Health NIH • Leland Stanford Junior University • US Department of Health and Human Services
Publication Number
US-8685411-B2
Publication Date
2014-04-01
Expiration Date
2025-07-01
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Abstract
The present invention relates to novel recombinant polypeptide antigens that may comprise subunit vaccines against rotavirus infection. Further, the present invention relates to methods for use of said antigens in the diagnosis, treatment and prevention of rotavirus infection.
Core Innovation
Rotaviruses are a leading cause of severe vomiting and diarrhea in young children worldwide, resulting in significant mortality and healthcare costs. Although a live oral rotavirus vaccine was introduced, it was withdrawn due to safety concerns, highlighting the urgent need for safe, effective, inexpensive, and heat-stable vaccines against rotavirus infection.
The invention addresses this problem by employing innovative structure-based vaccine design focusing on recombinant polypeptide antigens derived from fragments of the rotavirus neutralization antigen VP4—specifically, the VP8* core and the VP5* antigen domain. These polypeptides represent single well-folded, protease-resistant, soluble, and biochemically stable domains that contain all known neutralization epitopes of VP4. Recombinant versions, including fusions, fragments, variants, and derivatives, can be efficiently expressed and purified, making them suitable as subunit vaccine components that are inherently non-infectious and safe to produce.
Further, the invention utilizes high-resolution structural data and biochemical analyses to define key structural domains, elucidate mechanisms of viral entry, and provide foundational knowledge to rationally design improved antigens. These antigens may be incorporated into immunogenic compositions or vaccines formulated with pharmaceutically acceptable carriers and adjuvants, and can be used in methods for the diagnosis, treatment, and prevention of rotavirus infection in mammals, including humans.
Claims Coverage
The patent includes at least six claims focusing on soluble, isolated recombinant antigenic polypeptides with specific sequence identities and their variants, as well as immunogenic compositions comprising these sequences.
Recombinant antigenic polypeptide with defined sequence identity
A soluble, isolated recombinant antigenic polypeptide having at least about 85% amino acid identity to the entire amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2.
Inclusion of specific neutralizing epitopes in the polypeptide
The polypeptide comprises any one of the epitopes selected from the group consisting of: 8-1, 8-2, 8-3, and 8-4.
Fusion protein expression format
The polypeptide can be expressed as a fusion protein, allowing for modifications such as solubility enhancement, purification facilitation, or presentation enhancements.
Protease resistance of the polypeptide
The antigenic polypeptide is protease-resistant, contributing to stability and suitability in vaccine applications.
Immunogenic compositions with defined VP8* core sequences
Immunogenic compositions comprising the polypeptides of SEQ ID NO:1 or SEQ ID NO:2, representing VP8* core sequences from distinct rotavirus strains.
The claims cover soluble, recombinant antigenic polypeptides based on VP8* core sequences with specified sequence identity and neutralization epitopes, their protease-resistant properties, fusion protein formats, and immunogenic compositions comprising these polypeptides, thus addressing improved rotavirus vaccine candidates.
Stated Advantages
The antigens are homogeneous, pure, soluble, stable, protease-resistant, and efficiently produced recombinant polypeptides suitable for vaccine development.
The structure-based design allows presentation of known neutralization determinants, potentially leading to inexpensive, safe, and heat-stable vaccines.
Use of recombinant subunit vaccines circumvents safety issues related to live vaccines, providing non-infectious and safe production methods.
Broad heterotypic neutralizing antibody responses can be elicited, improving vaccine efficacy against diverse rotavirus strains.
Documented Applications
Use of recombinant VP8* and VP5* polypeptides as antigens in subunit vaccines for the prevention of rotavirus infection in mammals, including humans.
Formulation of immunogenic compositions or vaccines comprising these recombinant antigens with pharmaceutically acceptable carriers and adjuvants.
Use of the antigens and nucleic acids encoding them in methods for diagnosis, treatment, and prevention of rotavirus infection.
Development of kits including nucleic acids, polypeptides, antibodies, and instructions for diagnostic, preventative, and therapeutic purposes related to rotavirus infection.
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