Human rotavirus vaccine strains and diagnostics
Inventors
Jiang, Baoming • Glass, Roger I. • Wang, Yuhuan • Gentsch, Jon
Assignees
Centers of Disease Control and Prevention CDC • US Department of Health and Human Services
Publication Number
US-9974851-B2
Publication Date
2018-05-22
Expiration Date
2030-05-12
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Abstract
Immunogenic pharmaceutical compositions including a live, attenuated human rotavirus or an inactivated human rotavirus are provided which are useful for inducing an immunological response against the rotavirus in a subject. Methods of inducing an immunological response to a rotavirus in a subject are provided by administering an immunogenic pharmaceutical composition including a live, attenuated human rotavirus or an inactivated human rotavirus described herein.
Core Innovation
The invention provides immunogenic pharmaceutical compositions comprising a live, attenuated human rotavirus or an inactivated human rotavirus, useful for inducing an immunological response against rotavirus in a subject. These compositions may include one or more isolated rotavirus strains illustratively identified as strains CDC-9 or CDC-66, optionally including an adjuvant and a pharmaceutically acceptable carrier.
The invention addresses the need for vaccines against human rotavirus A of both common and less common types. The background highlights that rotavirus is the most common cause of severe diarrhea in children, causing an unacceptable number of deaths worldwide. Existing vaccines are limited in cross protection, especially against the G2 serotype, and the efficacy is reduced in low income countries. Furthermore, the suspension of use of certain vaccines like ROTARIX by the FDA due to contaminants has decreased vaccine availability.
Claims Coverage
The patent includes multiple independent claims broadly directed to immunogenic compositions comprising live, attenuated or inactivated human rotaviruses with specified protein identity, administration formulations, and methods for inducing immunological responses.
Immunogenic composition with specified rotavirus proteins and adjuvant
An immunogenic composition comprising a live, attenuated or inactivated human rotavirus and an adjuvant that increases immunogenicity, wherein the rotavirus comprises NSP1, NSP2, NSP3, NSP4, NSP5, VP1, VP2, VP3, VP4, VP5, VP6 and VP7 proteins each having greater than 95% identity to specific SEQ ID NOs associated with CDC-9 or CDC-66 strains.
Formulation with a pharmaceutically acceptable carrier for various administration routes
Compositions include a pharmaceutically acceptable carrier and are formulated for oral and parenteral administration to a subject.
Method of inducing immunological response by administering immunogenic composition
Methods for inducing an immunological response in a subject by administering an immunogenic amount of the compositions comprising CDC-9 or CDC-66 rotavirus strains and their specified protein sequences.
Immunogenic composition with defined amino acid substitutions
An immunogenic composition comprising rotavirus with NSP1 protein greater than 95% identical to SEQ ID NO: 3 with amino acid 122 as arginine, NSP5 with amino acid 45 as isoleucine, VP4 with specified amino acid residues at positions 51, 331, 364, 365, and 388, VP6 with amino acid 101 as valine, and corresponding other viral proteins having greater than 95% identity to specified SEQ ID NOs.
The claims collectively cover vaccine compositions including live attenuated or inactivated rotavirus strains CDC-9 and CDC-66 characterized by specified protein sequences with high identity to deposited SEQ ID NOs, formulations for administration, and methods of inducing immune responses, including compositions with particular amino acid variants.
Stated Advantages
The vaccine formulation with aluminum hydroxide (Al(OH)3) as adjuvant dramatically enhances total antibody titers in mice at different antigen concentrations.
In gnotobiotic piglet models, vaccination with inactivated rotavirus plus aluminum phosphate adjuvant provides significant protection against rotavirus infection, as shown by reduced or absent virus shedding compared to controls.
The vaccine compositions stimulate generation of neutralizing antibodies specific to rotavirus, indicating effective immune response induction.
Documented Applications
Vaccines for immunizing humans against rotavirus A infection and related disease.
Use in preventing rotavirus-induced severe diarrhea and related mortality in children worldwide.
Administration of immunogenic compositions orally or parenterally to induce protective immunity against multiple human rotavirus serotypes including G1 and G2 types.
Gnotobiotic piglet model studies for preclinical evaluation of vaccine immunogenicity and protective efficacy against rotavirus infection.
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