Multivalent VLP Conjugates

Abstract

The invention is directed to vaccines comprising capsular polysaccharides conjugated to one or more components of virus like particles (VLP), and methods for the administration of and methods for the manufacture of vaccines of the invention. Preferably vaccines of the invention generate a therapeutically effective response in an individual in need thereof to multiple strains and/or serotypes of the same or of different infectious agents. Preferably such vaccines generate a therapeutically effective immune response to all pathogenic strains and/or serotypes of the same infectious agent. In particular, the invention is directed to methods and compositions for the cost efficient administration of a vaccine to a patient in need thereof exposing the patient's immune system to only the immunogenic components that are likely to be beneficial for the generation of a protective immunological response, both efficacy and safety are increased and cost effectively.

1 . A vaccine against multiple serotypes of an infectious agent comprising virus like particles coupled to multiple polysaccharides each polysaccharide representing a serotype of the infectious agent. 
     
     
         2 . The vaccine of  claim 1 , wherein the virus like particles are obtained or derived from hepatitis virus, human papilloma virus, respiratory syncytial virus, flavivirus or combinations thereof. 
     
     
         3 . The vaccine of  claim 1 , wherein the multiple polysaccharides are covalently coupled via conjugation to one or more components of the virus like particles. 
     
     
         4 . The vaccine of  claim 3 , wherein the conjugation involves coupling via a cyanylating agent. 
     
     
         5 . The vaccine of  claim 4 , wherein the cyanylating agent comprises 1-cyano-4-(dimethylamino)-pyridinium tetrafluoroborate (CDAP), 1-cyanobenzotriazole (1-CBT), 2-cyanopyridazine-3 (2H)-One (2-CPO), 1-cyanoimidazole (1-CI), 1-cyano-4-pyrrolidinopyridinium tetrafluorborate (CPPT) or a combination thereof. 
     
     
         6 . The vaccine of  claim 1 , wherein the infectious agent is a virus, a bacterium, or a parasite. 
     
     
         7 . The vaccine of  claim 6 , wherein the virus comprises one or more of enterovirus, hepatitis virus, human immunodeficiency virus (HIV), human papilloma virus (HPV), influenza virus, pertussis virus, rubella virus, tetanus virus, varicella zoster virus (VZV), flavivirus, West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and combinations thereof. 
     
     
         8 . The vaccine of  claim 6 , wherein the bacterium comprises one or more of chlamydia, clostridium, diphtheria, meningococcal, streptococcal, staphylococcal, pneumococcal, bacillus or combinations thereof. 
     
     
         9 . The vaccine of  claim 6 , wherein the parasite comprises giardia, plasmodium or a combination thereof. 
     
     
         10 . The vaccine of  claim 1 , which does not require an adjuvant to generate a therapeutically effective response. 
     
     
         11 . The vaccine of  claim 1 , further comprising an adjuvant. 
     
     
         12 . The vaccine of  claim 11 , wherein the adjuvant comprises aluminum hydroxide with phosphate buffer. 
     
     
         13 . The vaccine of  claim 1 , which upon administration to a patient, generates a therapeutically effective immune response against the infectious agent. 
     
     
         14 . The vaccine of  claim 13 , wherein the therapeutically effective immune response comprises protection to an individual against a subsequent infection of the infectious agent and/or therapeutic treatment to an individual infected by the infectious agent. 
     
     
         15 . The vaccine of  claim 13 , wherein the therapeutically effective immune response provides protection against infection by multiple serotypes of the infectious agent. 
     
     
         16 . The vaccine of  claim 13 , wherein the therapeutically effective immune response comprises a humoral and/or a cellular immune response against the infectious agent. 
     
     
         17 . A vaccine against multiple serotypes of an infectious agent comprising virus like particles coupled to multiple polysaccharides and/or peptides wherein the multiple polysaccharide and/or peptides represent different serotypes of the infectious agent. 
     
     
         18 . The vaccine of  claim 17 , wherein the virus like particles are obtained or derived from hepatitis virus, human papilloma virus, respiratory syncytial virus, flavivirus or combinations thereof. 
     
     
         19 . The vaccine of  claim 17 , wherein the multiple polysaccharides and/or peptides are covalently coupled via conjugation to one or more components of the virus like particles. 
     
     
         20 . The vaccine of  claim 19 , wherein the conjugation involves coupling via a cyanylating agent. 
     
     
         21 . The vaccine of  claim 20 , wherein the cyanylating agent comprises 1-cyano-4-(dimethylamino)-pyridinium tetrafluoroborate (CDAP), 1-cyanobenzotriazole (1-CBT), 2-cyanopyridazine-3 (2H)-One (2-CPO), 1-cyanoimidazole (1-CI), 1-cyano-4-pyrrolidinopyridinium tetrafluorborate (CPPT) or a combination thereof. 
     
     
         22 . The vaccine of  claim 17 , wherein the infectious agent is a virus, a bacterium, or a parasite. 
     
     
         23 . The vaccine of  claim 22 , wherein the virus comprises one or more of enterovirus, hepatitis virus, human immunodeficiency virus (HIV), human papilloma virus (HPV), influenza virus, pertussis virus, rubella virus, tetanus virus, varicella zoster virus (VZV), flavivirus, West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and combinations thereof. 
     
     
         24 . The vaccine of  claim 22 , wherein the bacterium comprises one or more of chlamydia, clostridium, diphtheria, meningococcal, streptococcal, staphylococcal, pneumococcal, bacillus or combinations thereof. 
     
     
         25 . The vaccine of  claim 22 , wherein the parasite comprises giardia, plasmodium or a combination thereof. 
     
     
         26 . The vaccine of  claim 17 , which does not require an adjuvant to generate a therapeutically effective response. 
     
     
         27 . The vaccine of  claim 17 , further comprising an adjuvant. 
     
     
         28 . The vaccine of  claim 27 , wherein the adjuvant comprises aluminum hydroxide with phosphate buffer. 
     
     
         29 . The vaccine of  claim 17 , which upon administration to a patient, generates a therapeutically effective immune response against the infectious agent. 
     
     
         30 . The vaccine of  claim 29 , wherein the therapeutically effective immune response comprises protection to an individual against a subsequent infection of the infectious agent and/or therapeutic treatment to an individual infected by the infectious agent. 
     
     
         31 . The vaccine of  claim 29 , wherein the therapeutically effective immune response provides protection against infection by multiple serotypes of the infectious agent. 
     
     
         32 . The vaccine of  claim 29 , wherein the therapeutically effective immune response comprises a humoral and/or a cellular immune response against the infectious agent.