Improved poxviral vaccines

Abstract

The present application relates to novel administration regimens for poxviral vectors comprising nucleic acid constructs encoding antigenic proteins and invariant chains. In particular the use of said poxviral vectors for priming or for boosting an immune response is disclosed.

1 . A poxviral vector comprising a nucleic acid construct for use in priming or boosting an immune response, the nucleic acid construct comprising:
 (i) a nucleic acid sequence encoding at least one antigenic protein or antigenic fragment thereof operatively linked to   (ii) a nucleic acid encoding at least one invariant chain.   
     
     
         2 . The poxviral vector according to  claim 1 , wherein the at least one encoded invariant chain is of mammalian origin. 
     
     
         3 . The poxviral vector according to  claim 1 , wherein the encoded at least one invariant chain is characterized by at least one of the following features:
 (i) the endogenous KEY-region is deleted or substituted by a different sequence;   (ii) the methionine in positions 107 and 115 (human invariant chain) or in positions 90 and 98 (murine invariant chain) or the positions corresponding thereto in another invariant chain is substituted by another amino acid;   (iii) the first 16 amino acids of the wild-type human invariant chain sequence are deleted;   (iv) at least one sorting peptide is added to, removed from or replaces the endogenous sorting peptide of the invariant chain, and/or   (iv) at least one CLIP region is added to, removed from or replaces the endogenous CLIP region of the at least one invariant chain.   
     
     
         4 . The poxviral vector according to  claim 1 , wherein the encoded at least one invariant chain is a fragment of SEQ ID NO: 1 or SEQ ID NO: 3 of at least 40 consecutive amino acids or has at least 85% sequence identity to the same fragment of SEQ ID NO: 1 or SEQ ID NO: 3. 
     
     
         5 . The poxviral vector according to  claim 1 , wherein the at least one antigenic protein is a protein of a pathogenic organism, cancer-specific protein, or a protein associated with an abnormal physiological response. 
     
     
         6 . The poxviral vector according to  claim 5 , wherein the pathogenic organism is a virus, a bacterium, a protist or a multicellular parasite. 
     
     
         7 . The poxviral vector according to  claim 1 , wherein the poxvirus is selected from an orthopox, parapox, yatapox, avipox and molluscipox viral vector. 
     
     
         8 . The poxviral vector of  claim 7 , wherein the orthopox viral vector is a monkey pox viral vector, a cow pox viral vector or a vaccinia viral vector, preferably Modified Vaccinia Ankara (MVA). 
     
     
         9 . The poxviral vector according to  claim 1 , wherein the priming of the immune response is part of a homologous prime-boost vaccination regimen. 
     
     
         10 . The poxviral vector according to  claim 1 , wherein the priming of the immune response is part of a heterologous prime-boost vaccination regimen. 
     
     
         11 . The poxviral vector according to  claim 1 , wherein the poxviral vector is administered via intranasal, intramuscular, subcutaneous, intradermal, intragastric, oral and topical routes. 
     
     
         12 - 18 . (canceled) 
     
     
         19 . A method for stimulating an immune response comprising administering to a subject a composition comprising the poxviral vector of  claim 1 . 
     
     
         20 . The method of  claim 19 , further comprising administering a composition comprising one or more of the following:
 (i) a second vector comprising a nucleic acid sequence encoding at least a second antigenic protein or antigenic fragment thereof; or   (ii) a second antigenic protein or antigenic fragment thereof or   (iii) viral like particles.   
     
     
         21 . The method of  claim 20 , wherein the second viral vector is selected from adenoviral vector, poxviral vector, adeno-associated viral vector, lentiviral vector, alphavirus vector, measles virus vector, arenavirus vector, paramixovirus vector, baculovirus vector, naked DNA and viral like particles. 
     
     
         22 . The method of  claim 21 , wherein the adenoviral vector is a non-human great ape-derived adenoviral vector, preferably a chimpanzee or bonobo adenoviral vector. 
     
     
         23 . A method of  claim 20 , for use in a prime-boost vaccination regimen. 
     
     
         24 . The method of  claim 23 , wherein the poxviral vector is used for the priming of the immune response and the second viral vector or second antigenic protein of is used for boosting the immune response. 
     
     
         25 . The method of  claim 23 , wherein the second viral vector or second antigenic protein is used for the priming of the immune response and the poxviral vector is used for boosting the immune response. 
     
     
         26 . The method of  claim 23 , wherein the immune response is primed via an administration route selected from the group consisting of intranasal administration, intramusculuar administration, subcutaneous administration, intradermal administration, intragastric administration, oral administration and topical administration; and the immune response is boosted via an administration route selected from the group consisting of intranasal administration, intramusculuar administration, subcutaneous administration, intradermal administration, intragastric administration, oral administration and topical administration.