Methods for Enhancing Efficacy of a Vaccine by Administering an IL-4R Antagonist

Patent metadata

Field	Value
Publication number	US-2017239342-A1
Application number	US-201715436032-A
Country	US
Kind code	A1
Filing date	Feb 17, 2017
Priority date	Feb 19, 2016
Publication date	Aug 24, 2017
Grant date	—

Abstract

The present invention provides methods for enhancing the efficacy and/or safety of a vaccine. In certain embodiments, the invention provides methods to increase or potentiate the immune response to a vaccine in a subject in need thereof. The methods of the present invention comprise administering to a subject in need thereof an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody in combination with said vaccine. In certain embodiments, the methods of the present invention are used to afford enhanced protection to an infectious disease such as whooping cough.

First claim

1 - 94 . (canceled)

95 . A method for enhancing the efficacy and/or safety of a vaccine comprising:
(a) selecting a subject that is susceptible to a bacterial or viral infection; and (b) administering a vaccine specific to said bacterial or viral infection in combination with an IL-4R antagonist to the subject.

96 . The method of claim 95 , wherein the IL-4R antagonist is administered before, after or concurrent with the vaccine.

97 . The method of claim 96 , wherein the vaccine is administered at an initial dose followed by one or more subsequent (booster) doses.

98 . The method of claim 97 , wherein one or more doses of the IL-4R antagonist are administered before each dose of the vaccine.

99 . The method of claim 98 comprising administering a dose of the IL-4R antagonist concurrent with each dose of the vaccine.

100 . The method of claim 96 comprising administration of one or more doses of the IL-4R antagonist before the vaccine followed by a dose of the IL-4R antagonist concurrent with the vaccine, optionally followed by one or more doses of the IL-4R antagonist.

101 . The method of claim 100 , wherein each dose of the IL-4R antagonist comprises 1-10 mg/kg of the subject's weight.

102 . The method of claim 100 , wherein each dose comprises 10-600 mg of the IL-4R antagonist.

103 . The method of claim 94 , wherein the vaccine is against a bacterial or viral infection selected from the group consisting of pertussis, diphtheria, tetanus, tuberculosis, malaria, anthrax, cholera, typhoid, leprosy, Lyme's disease, streptococcal infection, E. coli infection, staphylococcal infection, plague, clostridial infection, meningococcal infection, pneumococcal infection, pneumonia, meningitis, sepsis, influenza, chickenpox, HIV infection, RSV infection, polio, small pox, rabies, rotavirus infection, papillomas, cervical cancer, Ebola, hepatitis, yellow fever, measles, mumps and Rubella infection.

104 . The method of claim 103 , wherein the vaccine is against pertussis.

105 . The method of claim 104 , wherein the pertussis vaccine is selected from the group consisting of whole-cell vaccine or acellular vaccine.

106 . The method of claim 105 , wherein the vaccine is acellular pertussis (aP) vaccine.

107 . The method of claim 95 , wherein the subject is allergic to the vaccine.

108 . The method of claim 95 , wherein enhancing the efficacy and/or safety of a vaccine comprises at least one of the effects selected from the group consisting of prevention of infection and transmission of infectious disease, increase in the duration of resistance to pathogen infection, faster pathogen clearance from infected host, reduction in pathogen load in infected organ, increase in T helper 1 (Th1) type antigen-specific IgG isotype antibodies, reduction or abrogation of IgE elicited by the vaccine, reduction in T helper 2 (Th2) response elicited by the vaccine, reduction in Th2-type antigen-specific IgG isotype antibodies, and reduction in allergic response to the vaccine.

109 . The method of claim 95 , wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that binds IL-4Rα and prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor.

110 . The method of claim 109 , wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 and IL-13 with both type 1 and type 2 IL-4 receptors.

111 . The method of claim 110 , wherein the antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and the light chain complementarity determining regions (LCDRs) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

112 . The method of claim 110 , wherein the antibody or antigen-binding fragment thereof comprises three HCDRs (HCDR1, HCDR2 and HCDR3) and three LCDRs (LCDR1, LCDR2 and LCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.

113 . The method of claim 112 , wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises the amino acid sequence of SEQ ID NO: 2.

114 . The method of claim 95 , wherein the IL-4R antagonist is dupilumab or a bioequivalent thereof.

Assignees

• Regeneron Pharma

Inventors

• Purcell Ngambo Lisa
• Graham Neil
• Murphy Andrew J
• Evans Robert

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P31/22

  for herpes viruses · CPC title