Kexin-derived vaccines to prevent or treat fungal infections

Abstract

A vaccine is disclosed that promotes CD4+ T cell-independent host defense mechanisms to defend against infection by fungi such as Pneumocystis spp. The vaccine may be used to prevent or to treat fimgal infections. The novel vaccine can provide protective immunity, even for immunocompromised individuals such as HIV patients having reduced levels of CD4+ T cells.

What is claimed: 
     
         1 . The protein mini-Kexin (SEQ ID NO 5). 
     
     
         2 . An isolated nucleic acid encoding the protein of  claim 1 . 
     
     
         3 . The nucleic acid of  claim 2 , wherein said nucleic acid has sequence SEQ ID NO 1 or SEQ ID NO 2. 
     
     
         4 . The nucleic acid of  claim 2 , wherein the codons of said nucleic acid are optimized to enhance expression in mammalian cells. 
     
     
         5 . The nucleic acid of  claim 4 , wherein said nucleic acid has sequence SEQ ID NO 3 or SEQ ID NO 4. 
     
     
         6 . A fusion protein that comprises mini-Kexin (SEQ ID NO 5), but that does not comprise the entire Kexin protein; and that further comprises a leader that promotes secretion of said fusion protein from a mammalian cell. 
     
     
         7 . An isolated nucleic acid encoding the fusion protein of  claim 6 . 
     
     
         8 . The fusion protein of  claim 6 , wherein said leader is an IgG C  leader, and wherein the fusion protein has sequence SEQ ID NO 6. 
     
     
         9 . An isolated nucleic acid encoding the fusion protein of  claim 8 . 
     
     
         10 . The fusion protein of  claim 6 , wherein said fusion protein comprises mini-Kexin and further comprises CD40L. 
     
     
         11 . An isolated nucleic acid encoding the fusion protein of  claim 10 . 
     
     
         12 . A vaccine comprising the protein of  claim 1 , and additionally comprising an adjuvant. 
     
     
         13 . The vaccine of  claim 12 , wherein the adjuvant comprises CD40L. 
     
     
         14 . A vaccine comprising the nucleic acid of  claim 2 , and additionally comprising an isolated nucleic acid that encodes an adjuvant. 
     
     
         15 . The vaccine of  claim 14 , wherein the encoded adjuvant comprises CD40L. 
     
     
         16 . A vaccine that comprises a live virus containing the nucleic acid of  claim 2 . 
     
     
         17 . A method of immunizing a mammalian patient against infection by  Pneumocystis,  said method comprising administering to the patient the vaccine of  claim 12 . 
     
     
         18 . A method of immunizing a mammalian patient against infection by  Pneumocystis,  said method comprising administering to the patient the vaccine of  claim 14 . 
     
     
         19 . A method of immunizing a mammalian patient against infection by  Pneumocystis,  said method comprising administering to the patient the fusion protein of  claim 10 . 
     
     
         20 . A method of immunizing a mammalian patient against infection by  Pneumocystis,  said method comprising administering to the patient the nucleic acid of  claim 11 . 
     
     
         21 . The method of  claim 20 , wherein the patient is a human. 
     
     
         22 . The method of  claim 21 , wherein the patient is immunocompromised. 
     
     
         23 . The method of  claim 21 , wherein the patient is not suffering adverse effects of  Pneumocystis  infection, and wherein said method affords protection against future infection by  Pneumocystis.    
     
     
         24 . The method of  claim 21 , wherein the patient is suffering adverse effects of  Pneumocystis  infection, and wherein said method ameliorates the  Pneumocystis  infection. 
     
     
         25 . The method of  claim 21 , wherein the patient is immunized a plurality of times to provide a stronger immune response than would be provided by a single immunization. 
     
     
         26 . The method of  claim 21 , wherein said method comprises one or more prime vaccinations and one or more boost vaccinations; and wherein the prime and boost vaccinations differ from one another in the location of administration, or the composition of the vaccine, or both. 
     
     
         27 . The method of  claim 26 , wherein the prime vaccination comprises intramuscular vaccination with a plasmid vaccine; and wherein the boost vaccination comprises intranasal vaccination or other mucosal vaccination with an adenovirus vaccine. 
     
     
         28 . A method of immunizing a mammalian patient against fungal infection, said method comprising administering to the patient the vaccine of  claim 12 . 
     
     
         29 . A method of immunizing a mammalian patient against fungal infection, said method comprising administering to the patient the vaccine of  claim 14 .