Human rotavirus G9P[6] strain and use as a vaccine
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-11759513-B2
Publication Date
2023-09-19
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 relates to an attenuated human rotavirus strain characterized as G9P[6], specifically a strain designated CDC-6, and pharmaceutical compositions including this virus or components thereof. These compositions can induce an immune response, including a protective immune response, against rotavirus infections and can be formulated as vaccines, particularly for children, such as infants, employing strategies like prime-boost immunization.
The problem addressed by the invention stems from the worldwide prevalence and impact of rotavirus, which causes severe diarrhea in children and is highly contagious with significant morbidity and mortality. Existing vaccines, such as ROTARIX®, primarily based on G1 strains, provide only partial cross-protection and have reduced efficacy against certain DS-1 like strains, including those with P6 specificity. The invention provides a novel attenuated G9P[6] rotavirus strain that overcomes limitations of current vaccines by inducing cross-protective immune responses against heterotypic rotavirus strains.
Claims Coverage
The claims define seven main inventive features focused on isolated polypeptides, nucleic acids, vectors, pharmaceutical compositions, and methods of inducing an immune response involving the G9P[6] rotavirus VP7 polypeptide and combinations with inactivated G1P[8] rotavirus.
Isolated polypeptide of VP7 amino acid sequence
An isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 6, corresponding to the VP7 polypeptide of attenuated G9P[6] rotavirus.
Isolated nucleic acid encoding the VP7 polypeptide
An isolated nucleic acid molecule encoding the polypeptide comprising the amino acid sequence of SEQ ID NO: 6.
Vector comprising the nucleic acid linked to heterologous promoter
A vector including the isolated nucleic acid molecule encoding SEQ ID NO: 6, operably linked to a heterologous promoter to enable expression.
Host cell transformed with the vector
An isolated host cell that has been transformed with the vector containing the nucleic acid encoding the VP7 polypeptide.
Pharmaceutical composition including VP7 polypeptide or encoding nucleic acid
A pharmaceutical composition comprising an effective amount of the isolated VP7 polypeptide (SEQ ID NO: 6), a nucleic acid encoding the polypeptide, or a vector encoding the nucleic acid, together with a pharmaceutically acceptable carrier.
Pharmaceutical composition further comprising inactivated G1P[8] rotavirus
A pharmaceutical composition as above further including an inactivated G1P[8] rotavirus, optionally heat inactivated (such as the CDC-9 strain) and optionally including an adjuvant.
Method of inducing immune response using pharmaceutical composition
A method of inducing an immune response to a rotavirus protein by administering an effective amount of the pharmaceutical composition comprising the VP7 polypeptide (or encoding nucleic acid or vector), a pharmaceutically acceptable carrier and an adjuvant, to a subject. The method can include prime and boost administration, be performed parenterally or intradermally, and can be combined with administration of attenuated or inactivated G1P[8] rotavirus.
The claims cover isolated VP7 polypeptides and their encoding nucleic acids, vectors and host cells, pharmaceutical compositions containing these components with or without inactivated G1P[8] rotavirus (e.g., CDC-9), and methods of inducing immune responses in subjects, including children, using these compositions with adjuvants and various administration routes.
Stated Advantages
The attenuated G9P[6] rotavirus strain induces an immune response without causing disease or diarrhea in the subject.
The vaccine composition provides homotypic and heterotypic immune responses, enhancing cross-protection against diverse rotavirus strains, including DS-1 like strains.
The attenuated strain CDC-6 exhibits favorable virological and molecular features, such as growth to high titers in Vero cells and stability of triple-layered particles, facilitating vaccine production.
Pharmaceutical compositions including both attenuated G9P[6] and inactivated G1P[8] rotaviruses may enhance protective immunity.
Formulations with adjuvants improve immunogenicity, enabling effective vaccination with lower antigen doses.
Documented Applications
Use in vaccines to induce protective immune responses against rotavirus infection in humans, particularly children under 5 or under 1 year of age.
Administration of attenuated or inactivated G9P[6] rotavirus as monovalent or combined vaccines (e.g., with inactivated or attenuated G1P[8] rotavirus strains like CDC-9 or commercial vaccines ROTARIX® and ROTATEQ®).
Formulation of vaccine compositions for oral or parenteral administration to subjects for prevention or treatment of rotavirus infections.
Inclusion of attenuated or inactivated rotavirus in combination vaccines with other pathogens such as diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis B, polio, and pneumococcal disease.
Use of isolated nucleic acid molecules and polypeptides from the G9P[6] rotavirus in pharmaceutical compositions to induce immune responses.
Prime and boost immunization strategies employing the attenuated G9P[6] rotavirus or compositions thereof to enhance immune protection.
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