Human rotavirus G9P[6] strain and use as a vaccine
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-11185581-B2
Publication Date
2021-11-30
Expiration Date
2036-09-28
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Abstract
Attenuated G9P[6] rotavirus is disclosed herein. In some embodiments, pharmaceutical compositions are disclosed that include an attenuated G9P[6] rotavirus, or a component thereof. These compositions can be used to induce an immune response, such as a protective immune response, to a rotavirus. The compositions can be used as vaccines, such as for children (infants), for example in a prime boost strategy.
Core Innovation
The invention disclosed relates to an attenuated human rotavirus strain G9P[6], referred to as CDC-6, and pharmaceutical compositions including this attenuated rotavirus or components thereof. These compositions are designed to induce an immune response in a subject, particularly a protective immune response against rotavirus infection. The compositions can serve as vaccines and may be administered to children, including infants, using a prime-boost strategy.
The background presented describes rotavirus as the most common cause of diarrhea in children worldwide, affecting nearly every child by age five, with significant morbidity and mortality. Existing vaccines, such as ROTARIX®, target primarily the G1 serotype and provide cross-protection but show reduced efficacy against DS-1 like strains in certain regions. Additionally, the diversity of rotavirus serotypes and genotypes causing disease underscores the need for vaccines that provide broad robust immunity, including against less common types such as G9P[6].
The invention addresses the problem of limited vaccine efficacy against DS-1 like rotavirus strains and the absence of attenuated G9P[6] rotavirus strains usable in vaccines. CDC-6, an attenuated G9P[6] strain, grows efficiently in cell culture and retains stability, making it suitable for vaccine development. The invention includes isolated nucleic acids and polypeptides from this strain for use in pharmaceutical compositions to induce immune responses to homotypic and heterotypic rotavirus strains.
Claims Coverage
The patent contains one independent claim directed to an isolated polypeptide and associated pharmaceutical compositions and methods. The claim coverage centers on the isolated polypeptide and related compositions and methods of inducing an immune response.
Isolated polypeptide with high sequence identity to VP4
An isolated polypeptide comprising an amino acid sequence at least 99.3% identical to the amino acid sequence set forth as SEQ ID NO: 4 (VP4 protein of the attenuated G9P[6] rotavirus).
Pharmaceutical compositions including the polypeptide and optionally inactivated G1P[8] rotavirus
Pharmaceutical compositions comprising an effective amount of the isolated VP4 polypeptide (or encoding nucleic acid or vector), further optionally comprising an inactivated G1P[8] rotavirus (such as heat-inactivated CDC-9 strain) and optionally including an adjuvant.
Methods of inducing immune response using the pharmaceutical composition
Methods for inducing an immune response to a rotavirus protein in a subject by administering an effective amount of the pharmaceutical composition, optionally including a prime and boost regimen, applicable to subjects with or without rotavirus infection and particularly human children under 5 or 1 year of age. The method may involve parenteral administration and optionally administering an attenuated or inactivated G1P[8] rotavirus.
The claims cover the isolated VP4 polypeptide of the attenuated G9P[6] strain and compositions comprising it, including combined formulations with inactivated G1P[8] rotavirus and adjuvants, as well as methods for vaccination and immune response induction in humans, specifically pediatric subjects.
Stated Advantages
The attenuated G9P[6] rotavirus strain CDC-6 grows efficiently in cell culture to high titers and exhibits stability useful for vaccine production.
The vaccine can induce protective immune responses against multiple rotavirus genogroups including DS-1 like and Wa-like strains.
The composition can provide homotypic and heterotypic cross-protection, expanding vaccine coverage beyond common strains.
Inclusion of aluminum hydroxide adjuvant enhances immune response to the rotavirus antigen.
The vaccine can be formulated for oral or parenteral administration, suitable for pediatric use including infants under one year.
Documented Applications
Use of attenuated G9P[6] rotavirus strain CDC-6 as a live oral or inactivated vaccine to induce an immune response against rotavirus infection in children.
Pharmaceutical compositions combining attenuated or inactivated G9P[6] rotavirus with inactivated G1P[8] rotavirus strains for enhanced vaccination.
Administration of vaccine compositions prophylactically to prevent diarrhea caused by rotavirus strains in infants and young children.
Use in prime-boost immunization regimens for protective immune response induction.
Inclusion of inactivated attenuated rotavirus in multivalent vaccines targeting other pathogens, including diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis B, polio, and pneumococcal disease.
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