Mva expressing modified hiv envelope, gag and pol genes

Abstract

The invention provides modified virus Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing human immunodeficiency virus (HIV) env, gag, and pol genes.

1 - 30 . (canceled) 
     
     
         31 . A recombinant MVA viral vector comprising
 i) a sequence that encodes one or more antigens selected from HIV-1 Gag, HIV-1 Pol, Vif, Vpr, Tat, Rev, Vpu and Nef, and   ii) a sequence that encodes the gp120 protein and membrane spanning domain and ectodomain of gp41 protein of HIV-1 Env.   
     
     
         32 . The vector of  claim 31 , wherein the HIV-1 sequences are inserted into one or more of deletions I, II, III, IV, V, or VI of MVA. 
     
     
         33 . The vector of  claim 32 , wherein at least one of the HIV-1 sequences is inserted into deletion III of MVA. 
     
     
         34 . The vector of  claim 31 , wherein the sequence encoding the antigen is under the control of a promoter compatible with poxvirus expression systems. 
     
     
         35 . The vector of  claim 34 , wherein the promoter is selected from Psy II or PmH5. 
     
     
         36 . The vector of  claim 31 , wherein the vector expresses HIV Vif, Vpr, Tat, Rev, Vpu and Nef. 
     
     
         37 . The vector of  claim 31 , wherein the HIV-1 Env is optionally deleted of subsequences. 
     
     
         38 . The vector of  claim 31 , wherein the HIV-1 Env lacks part or all of the cytoplasmic domain of gp41. 
     
     
         39 . The vector of  claim 31 , wherein the sequence encoding the HIV-1 Env gp120 and gp41 protein is truncated of 115 COOH-terminal amino acids of full-length HIV-1 Env. 
     
     
         40 . The vector of  claim 31 , wherein regions of the gp120 surface and gp41 transmembrane cleavage are deleted. 
     
     
         41 . The vector of  claim 31 , wherein the HIV-1 Gag is optionally deleted of subsequences. 
     
     
         42 . The vector of  claim 31 , wherein regions of the HIV-1 Gag encoding the matrix protein (p17), regions of the capsid protein (p24), regions of the nucleocapsid protein (p7), and regions of p6 (the C-terminal peptide of the Gag polyprotein) are deleted. 
     
     
         43 . The vector of  claim 31 , wherein expression of the sequences forms noninfectious virus-like particles. 
     
     
         44 . A pharmaceutical composition comprising the vector of  claim 31  and a pharmaceutically acceptable carrier. 
     
     
         45 . The pharmaceutical composition of  claim 44 , wherein the pharmaceutically acceptable carrier is selected from physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. 
     
     
         46 . The pharmaceutical composition of  claim 44 , wherein the vector is formulated for intradermal, intramuscular, mucosal, intravenous, cutaneous, or subcutaneous administration. 
     
     
         47 . A method of inducing an immune response to HIV, comprising administering an effective amount of the recombinant MVA vector of claim  1 , wherein expression of the one or more antigens encoded by the vector induces an immune response to the one or more antigens. 
     
     
         48 . The method of  claim 47  wherein the immune response is a CD8+ T cell immune response or an antibody immune response. 
     
     
         49 . A method of boosting an immune response to HIV comprising administering an effective amount of the recombinant MVA vector of claim  1 , wherein expression of the one or more antigens encoded by the vector boosts a CD8+ T cell immune response to the one or more antigens.