Human rotavirus strains and vaccines
Inventors
Jiang, Baoming • Glass, Roger I. • Wang, Yuhuan • Gentsch, Jon
Assignees
US Department of Health and Human Services
Publication Number
US-11786589-B2
Publication Date
2023-10-17
Expiration Date
2030-05-12
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Abstract
A vaccine composition and method of vaccination are provided useful for immunizing a subject against a rotavirus. The vaccines include rotavirus strains CDC-9 and CDC-66, fragments thereof, homologues thereof, or combinations thereof. Inventive vaccines may include a fragment of CDC-9, CDC-66, homologues thereof, or combinations thereof. Methods of inducing an immunological response are provided by administering an inventive vaccine.
Core Innovation
The invention provides vaccine compositions and methods of vaccination useful for immunizing a subject against rotavirus. The vaccines include isolated human rotavirus A strains CDC-9 and CDC-66, fragments thereof, homologues thereof, or combinations thereof. These vaccines can be live attenuated or inactivated rotavirus strains, and may be administered parenterally or orally. The invention also includes vaccines comprising a pharmaceutically acceptable carrier admixed with at least two rotavirus strains characterized by various G and P group serotypes, including specifically G1 and G2 groups, and combinations thereof.
The problem addressed by the invention lies in the global health burden caused by rotavirus, especially in children where it is the most common cause of severe diarrhea leading to significant mortality worldwide. Existing vaccines have limitations in their efficacy, especially concerning genotypic differences between rotavirus strains, such as the G1 and G2 serotypes which belong to different genetic lineages, leading to limited cross-protection. Additionally, there is a decline in available vaccines due to issues like contamination in certain vaccines and reduced vaccine efficacy in low-income countries. Therefore, there is a continuous need for robust vaccines effective against diverse rotavirus strains.
Claims Coverage
The claims include a set of inventive features related to isolated nucleic acid molecules encoding specific rotavirus non-structural proteins and VP4 proteins with defined sequence identities and amino acid substitutions, as well as expression vectors and methods of producing these proteins.
Isolated nucleic acid molecules encoding rotavirus NSP and VP4 proteins with defined sequence identities and substitutions
The invention includes isolated nucleic acid molecules encoding rotavirus non-structural proteins NSP1, NSP2, NSP5, or VP4 proteins, where the sequences have greater than 95% identity to specified SEQ ID NOs, and where specific amino acid positions have designated residues, such as arginine at position 122 for NSP1 SEQ ID NO: 3, or phenylalanine at position 331 in VP4 SEQ ID NO: 27.
Nucleic acids encoding rotavirus proteins with specific amino acid sequences
The claims specify nucleic acid molecules encoding NSP1, NSP2, NSP5, or VP4 proteins that comprise or consist of specified SEQ ID NOs including SEQ ID NO: 3 for NSP1, SEQ ID NO: 15 or 96 for NSP5, SEQ ID NO: 78 for NSP2, and SEQ ID NOs: 27 or 120 for VP4 proteins.
Expression vectors comprising the isolated nucleic acid molecules
The invention includes expression vectors comprising any of the isolated nucleic acid molecules operably linked to promoters, such as a T7 promoter, and viral vectors.
Host cells transfected with expression vectors for rotavirus protein production
The invention covers isolated host cells transfected with the expression vectors capable of producing the rotavirus NSP or VP4 proteins.
Methods of producing rotavirus proteins using transfected host cells
Methods are provided for producing rotavirus NSP or VP4 proteins by culturing the transfected host cells in vitro and isolating the proteins from the host cells.
The claims comprehensively cover isolated nucleic acids encoding specific rotavirus non-structural and VP4 proteins with defined sequence identities and amino acid residues, their incorporation into expression vectors and host cells, and methods for producing the proteins, highlighting molecular and recombinant aspects of the invention.
Stated Advantages
The vaccine formulation including CDC-9 or CDC-66 rotavirus strains, particularly when adjuvanted with aluminum phosphate, dramatically enhances antibody titers and provides protective immunity against rotavirus infection as demonstrated in animal models.
The invention provides protection against diverse rotavirus strains by including strains from different serotype groups (G1 and G2), addressing limited cross-protection issues observed with existing vaccines.
The CDC-9 and CDC-66 strains have well-documented passaging history and can be adapted for growth in vaccine production-qualified cell lines, ensuring consistency and quality in vaccine production.
Inactivated rotavirus vaccines formulated with adjuvants such as aluminum phosphate induce strong neutralizing antibody responses and significantly reduce viral shedding and disease in animal models, validating their efficacy.
Documented Applications
Use as vaccine compositions comprising isolated rotavirus strains CDC-9 and CDC-66 or their fragments/homologues to immunize human subjects against rotavirus.
Administration of vaccines including live attenuated or inactivated rotavirus strains or antigenic portions thereof, parenterally or orally, to induce protective immunological responses.
Preparation of vaccines including at least two rotavirus strains of defined G and P serotypes to achieve broad protection.
Production of rotavirus proteins using recombinant expression systems for use as antigens in vaccines or for other immunological applications.
Use in inducing neutralizing antibody responses and protection against rotavirus infection as demonstrated in mouse and gnotobiotic piglet models.
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