Human rotavirus vaccine strains and diagnostics
Inventors
Jiang, Baoming • Glass, Roger I. • Wang, Yuhuan • Gentsch, Jon
Assignees
US Department of Health and Human Services
Publication Number
US-10500269-B2
Publication Date
2019-12-10
Expiration Date
2030-05-12
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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 rotavirus strains CDC-9 and CDC-66, fragments, homologues, or combinations thereof. These vaccines may be live attenuated or inactivated, optionally combined with a pharmaceutically acceptable carrier and an adjuvant. Methods of inducing an immunological response by administering these vaccines are also disclosed.
The problem addressed is the continuing need for effective vaccines against the diversity of human rotavirus A strains, especially including both common and less common types such as G1 and G2 serotypes. Existing vaccines have limitations, including limited cross-protection against diverse rotavirus strains, reduction in efficacy in low-income countries, and regulatory suspensions due to contamination concerns. There is a critical need for robust vaccines capable of generating immunity against multiple rotavirus strains to reduce the unacceptable number of deaths from rotavirus-mediated disease in children worldwide.
Claims Coverage
The claims present inventive features related to isolated rotavirus proteins, immunogenic compositions incorporating these proteins or whole rotavirus strains, and methods of inducing immune responses.
Isolated VP4 protein with specific amino acid identities and residues
An isolated VP4 protein having greater than 95% identity to SEQ ID NO: 27 or SEQ ID NO: 120, with defined amino acid residues at specified positions unique to each sequence.
Immunogenic compositions comprising VP4 protein and pharmaceutically acceptable carrier
Compositions comprising the isolated VP4 protein and a pharmaceutically acceptable carrier suitable for administration.
Methods of inducing immune response by administering immunogenic compositions
Procedures of administering an immunogenic amount of compositions containing the VP4 protein to induce an immunological response against rotavirus.
Immunogenic compositions comprising live attenuated or inactivated human rotavirus and adjuvant with defined protein identities
Compositions including live attenuated or inactivated human rotavirus containing NSP1, NSP2, NSP3, NSP4, NSP5, VP1, VP2, VP3, VP4, VP6, and VP7 proteins each having greater than 95% identity to specified SEQ ID NOs, formulated for intradermal or intramuscular administration, optionally with adjuvants to increase immunogenicity.
Immunogenic compositions with proteins comprising exact amino acid sequences
Compositions wherein each rotavirus protein comprises the precise amino acid sequences as set forth in specific SEQ ID NOs for CDC-9 or CDC-66 strains.
Methods of intradermal or intramuscular administration to induce an immune response
Administering an immunogenic amount of the immunogenic compositions containing defined rotavirus proteins via intradermal or intramuscular routes to induce immune responses.
Immunogenic compositions with rotavirus proteins having defined amino acid substitutions at specific residues
Compositions of live attenuated or inactivated human rotavirus with characterized amino acid substitutions at specific positions in certain NSP and VP proteins, formulated for intradermal or intramuscular administration, optionally with an adjuvant and pharmaceutically acceptable carrier.
The claims cover isolated VP4 proteins with defined sequence identities and amino acid residues, immunogenic compositions including these proteins or whole rotavirus strains with defined protein identities or sequences, inclusion of adjuvants, and methods of administration to induce immune responses against rotavirus.
Stated Advantages
The vaccine compositions are capable of inducing immunological responses sufficient to prevent or ameliorate signs or symptoms of rotavirus-mediated disease.
The inclusion of at least two rotavirus strains with different G and P serotypes enhances immunity across diverse rotavirus variants.
Adjuvant formulations, such as with aluminum hydroxide or phosphate, increase immunogenicity and protective efficacy of the vaccine.
The vaccine strains CDC-9 and CDC-66 have complete passage history and documentation under Good Laboratory Practice Guidelines, supporting controlled and standardized vaccine production.
Vaccines provide effective cross-protection including against prevalent human rotavirus A G1 and G2 serotypes, addressing gaps in existing vaccines' cross-protection abilities.
Documented Applications
Human vaccination against rotavirus-mediated disease to prevent severe diarrhea and associated mortality.
Development and production of vaccines including live attenuated or inactivated rotavirus strains for parenteral or oral administration.
Use of rotavirus polypeptides or immunogenic fragments in vaccine formulations to induce an immune response.
Diagnostic applications involving isolated rotavirus proteins, polypeptides, or nucleic acids derived from the CDC-9 and CDC-66 strains.
Animal models such as gnotobiotic piglet models to test vaccine immunogenicity and protective efficacy against rotavirus infection.
Interested in licensing this patent?