Influenza virus vaccination regimens
AssigneeIcahn School of Medicine at Mount Sinai
InventorsPeter Palese, Adolfo Garcia-Sastre, Florian Krammer
Life of this patent
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Abstract
Provided herein are immunization regimens for inducing an immune response (e.g., an antibody response) against influenza virus. In specific aspects, the immunization regimens involve the administration of a chimeric hemagglutinin (HA), a headless HA or another influenza virus stem domain based construct (e.g., the HA stem domain or a fragment thereof) to a subject. In certain aspects, the immunization regimens also involve the administration of an influenza virus neuraminidase immunogen.
Claims38
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising an influenza virus neuraminidase polypeptide and a live attenuated influenza virus engineered to express a first chimeric hemagglutinin (HA), wherein the first chimeric HA comprises a first influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the first influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising an inactivated influenza virus comprising a second chimeric HA, wherein the second chimeric HA comprises a second influenza virus HA globular head domain and the HA stem domain polypeptide, wherein the second influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide, and wherein the first influenza virus HA globular head domain is different than the second influenza virus HA globular head domain.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising a live attenuated influenza virus engineered to express a first chimeric hemagglutinin (HA), wherein the first chimeric HA comprises a first influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the first influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising an influenza virus neuraminidase polypeptide and an inactivated influenza virus comprising a second chimeric HA, wherein the second chimeric HA comprises a second influenza virus HA globular head domain and the HA stem domain polypeptide, wherein the second influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide, and wherein the first influenza virus HA globular head domain is different than the second influenza virus HA globular head domain.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising an influenza virus neuraminidase polypeptide and a live attenuated influenza virus engineered to express a chimeric HA, wherein the chimeric HA comprises an influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising an inactivated virus, wherein inactivated virus comprises a stem domain that is of the same subtype or strain as the influenza virus HA stem domain polypeptide.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising a live attenuated influenza virus engineered to express a chimeric HA, wherein the chimeric HA comprises a influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising an inactivated virus and an influenza virus neuraminidase polypeptide, wherein inactivated virus comprises a stem domain that is of the same subtype or strain as the influenza virus HA stem domain polypeptide.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising an influenza virus neuraminidase polypeptide and a first chimeric hemagglutinin (HA), wherein the first chimeric HA comprises a first influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the first influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising a second chimeric HA, wherein the second chimeric HA comprises a second influenza virus HA globular head domain and the HA stem domain polypeptide, wherein the second influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide, and wherein the first influenza virus HA globular head domain is different than the second influenza virus HA globular head domain.
A method for immunizing against influenza virus in a human subject, comprising
- (a) administering to the subject a first vaccine formulation comprising a first chimeric hemagglutinin (HA), wherein the first chimeric HA comprises a first influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the first influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising an influenza virus neuraminidase polypeptide and a second chimeric HA, wherein the second chimeric HA comprises a second influenza virus HA globular head domain and the HA stem domain polypeptide, wherein the second influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide, and wherein the first influenza virus HA globular head domain is different than the second influenza virus HA globular head domain.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising a first chimeric hemagglutinin (HA), wherein the first chimeric HA comprises a first influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the first influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide, and wherein the first influenza virus HA globular head domain comprises one or more antigenic peptides from influenza virus neuraminidase;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising a second chimeric HA, wherein the second chimeric HA comprises a second influenza virus HA globular head domain and the HA stem domain polypeptide, wherein the second influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide, and wherein the first influenza virus HA globular head domain is different than the second influenza virus HA globular head domain.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising a first chimeric hemagglutinin (HA), wherein the first chimeric HA comprises a first influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the first influenza virus HA globular head domain is heterologous to the HA stem domain polypeptides;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine formulation comprising a second chimeric HA, wherein the second chimeric HA comprises a second influenza virus HA globular head domain and the HA stem domain polypeptide, wherein the second influenza virus globular head domain is heterologous to the HA stem domain polypeptide, and wherein the second influenza virus HA globular head domain comprises one or more antigenic peptides from influenza virus neuraminidase, and wherein the first influenza virus HA globular head domain is different than the second influenza virus HA globular head domain.
A method for immunizing against influenza virus in a human subject, comprising:
- (a) administering to the subject a first vaccine formulation comprising a chimeric hemagglutinin (HA), wherein the chimeric HA comprises an influenza virus HA globular head domain and an influenza virus HA stem domain polypeptide, wherein the influenza virus HA globular head domain is heterologous to the HA stem domain polypeptide;
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- (b) a certain time after the administration of the first vaccine formulation, administering to the subject a second vaccine comprising an influenza virus neuraminidase polypeptide.
A method for immunizing against influenza virus in a human subject, comprising administering to the subject a vaccine formulation comprising three chimeric HAs, an influenza virus neuraminidase polypeptide from an N1, an influenza virus neuraminidase polypeptide from an N2, and an influenza virus neuraminidase polypeptide from an influenza B virus, wherein the first chimeric HA comprises a stem domain polypeptide from an H1 influenza virus and a first HA globular head domain, the second chimeric HA comprises a stem domain polypeptide from an H3 influenza virus and a second HA globular head domain, and the third chimeric HA comprises a stem domain polypeptide from an influenza B virus and a third HA globular head domain, wherein the first, second and third HA globular head domains are each from a different subtype or strain of influenza virus hemagglutinin, and wherein the HA globular head domain of each chimeric HA is heterologous to the stem domain polypeptide of each chimeric HA.
A method for immunizing against influenza virus in a human subject, comprising administering to the subject a vaccine formulation comprises three vectors, an influenza virus neuraminidase polypeptide from an N1, an influenza virus neuraminidase polypeptide from an N2, and an influenza virus neuraminidase polypeptide from an influenza B virus, wherein each vector comprises a chimeric HA, wherein the first vector comprises a first chimeric HA comprising a stem domain polypeptide from an H1 influenza virus and a first HA globular head domain, the second vector comprises a second chimeric HA comprising a stem domain polypeptide from an H3 influenza virus and a second HA globular head domain, and the third vector comprises a third chimeric HA comprising a stem domain polypeptide from an influenza B virus and a third HA globular head domain, wherein the first, second and third HA globular head domains are each from a different subtype or strain of influenza virus hemagglutinin, and wherein the HA globular head domain of each chimeric HA is heterologous to the stem domain polypeptide of each chimeric HA.
A vaccine formulation comprising three chimeric HAs, an influenza virus neuraminidase polypeptide from an N1, an influenza virus neuraminidase polypeptide from an N2, and an influenza virus neuraminidase polypeptide from an influenza B virus, wherein the first chimeric HA comprises a stem domain polypeptide from an H1 influenza virus and a first HA globular head domain, the second chimeric HA comprises a stem domain polypeptide from an H3 influenza virus and a second HA globular head domain, and the third chimeric HA comprises a stem domain polypeptide from an influenza B virus and a third HA globular head domain, wherein the first, second and third HA globular head domains are each from a different subtype or strain of influenza virus hemagglutinin, and wherein the HA globular head domain of each chimeric HA is heterologous to the stem domain polypeptide of each chimeric HA.
A vaccine formulation comprising three vectors, an influenza virus neuraminidase polypeptide from an N1, an influenza virus neuraminidase polypeptide from an N2, and an influenza virus neuraminidase polypeptide from an influenza B virus, wherein each vector comprises a chimeric HA, wherein the first vector comprises a first chimeric HA comprising a stem domain polypeptide from an H1 influenza virus and a first HA globular head domain, the second vector comprises a second chimeric HA comprising a stem domain polypeptide from an H3 influenza virus and a second HA globular head domain, and the third vector comprises a third chimeric HA comprising a stem domain polypeptide from an influenza B virus and a third HA globular head domain, wherein the first, second and third HA globular head domains are each from a different subtype or strain of influenza virus hemagglutinin, and wherein the HA globular head domain of each chimeric HA is heterologous to the stem domain polypeptide of each chimeric HA.
Dependencies are inferred from the claim text.