Combination vaccines with low dose of hib conjugate

Abstract

Provided herein are combination vaccines comprising antigens for protecting a subject against at least diphtheria, tetanus, pertussis and Hib, wherein: (a) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; (b) the concentration of the Hib conjugate in the vaccine is <15 μg/ml; and (c) the Hib conjugate has never been lyophilised.

1 . A combination vaccine comprising antigens for protecting a subject against at least diphtheria (‘D’), tetanus (‘T’), pertussis (‘P’) and  Haemophilus influenzae  type b (‘Hib’), wherein: (a) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; (b) the concentration of the Hib conjugate in the vaccine is <15 μg/ml; and (c) the Hib conjugate has never been lyophilised. 
   
   
       2 . A vial having a piercable seal and containing a combination vaccine, which combination vaccine comprises antigens for protecting a subject against at least diphtheria, tetanus, pertussis and  H. influenzae  type b (‘Hib’), wherein the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide, and wherein: (a) the concentration of the Hib conjugate in the vaccine is <15 μg/ml, and (b) the vial's piercable seal has not been pierced. 
   
   
       3 . A hermetically-sealed container containing a combination vaccine comprising antigens for protecting a subject against at least diphtheria, tetanus, pertussis and  H. influenzae  type b (‘Hib’), wherein the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide, and wherein the concentration of the Hib conjugate in the vaccine is <15 μg/ml. 
   
   
       4 . A process for preparing a combination vaccine comprising antigens for protecting a subject against at least diphtheria, tetanus, pertussis and  H. influenzae  type b (‘Hib’), wherein the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide, and the concentration of Hib conjugate in the vaccine is <15 μg/ml, characterised in that the process does not include one or both of the following steps (a) a step of lyophilisation of the Hib conjugate antigen; (b) a step of packaging the diphtheria, tetanus and pertussis antigens in admixed form separately from the Hib conjugate antigen. 
   
   
       5 . A process for inserting a combination vaccine into a container, wherein: (a) the vaccine that comprises antigens for protecting a subject against at least diphtheria, tetanus, pertussis and  H. influenzae  type b (‘Hib’); (b) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; and (c) the concentration of the Hib conjugate in the vaccine is <15 μg/ml. 
   
   
       6 . A process for attaching a label to a container, wherein: (a) the container contains a combination vaccine that comprises antigens for protecting a subject against at least diphtheria, tetanus, pertussis and  H. influenzae  type b (‘Hib’); (b) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; and (c) the concentration of the Hib conjugate in the vaccine is <15 μg/ml. 
   
   
       7 . A process for inserting a combination vaccine into a container and then extracting the vaccine from the container, wherein: (a) the vaccine comprises antigens for protecting a subject against at least diphtheria, tetanus, pertussis and  H. influenzae  type b (‘Hib’); (b) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; and (c) the concentration of the Hib conjugate in the vaccine is <15 μg/ml. 
   
   
       8 . A combination vaccine comprising antigens for protecting a subject against at least diphtheria (‘D’), tetanus (‘T’), pertussis (‘P’) and  H. influenzae  type b (‘Hib’), wherein: (a) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; (b) the concentration of the Hib conjugate in the vaccine is <15 μg/ml; and (c) the vaccine (i) does not contain an aluminium hydroxide adjuvant and/or (ii) does not contain an aluminium potassium sulphate adjuvant. 
   
   
       9 . The vaccine of  claim 8 , comprising an aluminium phosphate adjuvant. 
   
   
       10 . The vaccine of  claim 9 , wherein the Hib conjugate is not adsorbed to the aluminium phosphate adjuvant. 
   
   
       11 . The vaccine, vial, container or process of any preceding claim, where the diphtheria antigen comprises a diphtheria toxoid, the tetanus antigen comprises a tetanus toxoid, and the pertussis antigen comprises a cellular pertussis component. 
   
   
       12 . The vaccine, vial, container or process of any preceding claim, where the conjugate comprises a CRM 197  carrier, a tetanus toxoid carrier or an outer membrane complex of  N. meningitidis  carrier. 
   
   
       13 . The vaccine, vial, container or process of any preceding claim, where the conjugate comprises an oligosaccharide fragment of the Hib polyribosylribitol phosphate. 
   
   
       14 . The vaccine, vial, container or process of any preceding claim, wherein the combination vaccine further comprises a surface antigen from hepatitis B virus. 
   
   
       15 . The vaccine, vial, container or process of any preceding claim, wherein the combination vaccine further comprises a polio antigen. 
   
   
       16 . A method for raising an antibody response in a mammal, comprising administering the vaccine of any preceding claim to the mammal.