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

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.

1 . A method for reducing IgE induced by a vaccine in a subject, the method comprising administering an interleukin-4 receptor (IL-4R) antagonist to the subject, wherein the IL-4R antagonist is an anti-IL-4R antibody, or an antigen-binding fragment thereof, that 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; and wherein the IL-4R antagonist is administered before or concurrent with the vaccine. 
     
     
         2 . The method of  claim 1 , wherein the IL-4R antagonist is administered to the subject before the vaccine. 
     
     
         3 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the IL-4R antagonist is administered concurrent with the vaccine. 
     
     
         14 - 96 . (canceled) 
     
     
         97 . The method of  claim 1 , 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 97  comprising administering a dose of the IL-4R antagonist concurrent with each dose of the vaccine. 
     
     
         100 . (canceled) 
     
     
         101 . The method of  claim 1 , wherein each dose of the IL-4R antagonist comprises 1-10 mg/kg of the subject's weight. 
     
     
         102 . The method of  claim 1 , wherein each dose comprises 10-600 mg of the IL-4R antagonist. 
     
     
         103 - 108 . (canceled) 
     
     
         109 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 or IL-13, or both with a type 1 or type 2 IL-4 receptor. 
     
     
         110 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 with both type 1 and type 2 IL-4 receptors. 
     
     
         111 - 112 . (canceled) 
     
     
         113 . The method of  claim 1 , 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 1 , wherein the IL-4R antagonist is dupilumab or a bioequivalent thereof. 
     
     
         115 . The method of  claim 1 , wherein each dose of the IL-4R antagonist comprises 1 mg/kg, 2 mg/kg, 3 mg/kg, 5 mg/kg or 6 mg/kg of the subject's weight. 
     
     
         116 . The method of  claim 1 , wherein each dose of the IL-4R antagonist comprises 200 mg or 300 mg of the IL-4R antagonist. 
     
     
         117 . The method of  claim 1 , wherein each dose of the IL-4R antagonist comprises 100 mg of the IL-4R antagonist. 
     
     
         118 . The method of  claim 1 , wherein the IL-4R antagonist is administered once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks. 
     
     
         119 . The method of  claim 1 , wherein the IL-4R antagonist is administered subcutaneously. 
     
     
         120 . The method of  claim 1 , wherein the vaccine comprises an acellular pertussis vaccine. 
     
     
         121 . The method of  claim 120 , wherein the vaccine is a DTaP vaccine or a Tdap vaccine. 
     
     
         122 . The method of  claim 1 , wherein the IL-4R antagonist is contained in a container that is a syringe, a pen delivery device, or an autoinjector delivery device. 
     
     
         123 . The method of  claim 122 , wherein the IL-4R antagonist is contained in a syringe. 
     
     
         124 . The method of  claim 122 , wherein the IL-4R antagonist is contained in a pen delivery device. 
     
     
         125 . The method of  claim 124 , wherein the pen delivery device is a prefilled pen delivery device. 
     
     
         126 . The method of  claim 122 , wherein the IL-4R antagonist is contained in an autoinjector delivery device.