Paramyxovirus Immunogens and Related Materials and Methods

Abstract

Described herein are methyltransferase (MTase)-defective recombinant viruses as vaccines for human metapneumovirus (hMPV), human respiratory syncytial virus (hRSV), and human parainfluenza virus type 3 (PIV3); as well as related materials and methods.

What is claimed is: 
     
         1 . A recombinant paramyxovirus composition comprising a nucleic acid molecule which encodes a defective mRNA cap MTase in large (L) polymerase gene in a paramyxovirus viral genome;
 wherein the nucleic acid molecule which encodes a defective mRNA cap MTase carries at least one mutation in the MTase catalytic site;   wherein the at least one mutation in the MTase catalytic site is in at least one of the K-D-K-E tetrad sites; and,   wherein the paramyxovirus is human metapneumovirus (hMPV) and the at least one K-D-K-E tetrad site mutation is at least one of rhMPV-K1673A, rhMPV-D1779A, rhMPV-K1817A, rhMPV-E1848A, and rhMPV-E1848Q.   
     
     
         2 . The recombinant paramyxovirus composition of  claim 1 , wherein the nucleic acid molecule which encodes a defective mRNA cap MTase carries at least one mutation in the SAM binding site. 
     
     
         3 . The recombinant paramyxovirus composition according to  claim 1 , wherein the at least one mutation in the SAM binding site is in the G×G×G . . . D/E/W site;
 wherein the paramyxovirus is human metapneumovirus (hMPV) and the at least one mutation in the G×G×G . . . D/E/W site is at least one of rhMPV-G1696A, rhMPV-G1698A, rhMPV-G1700A, and rhMPV-D1755A. 
 
     
     
         4 . The recombinant paramyxovirus composition of  claim 1 , wherein the nucleic acid molecule which encodes a defective mRNA cap MTase carries at least one mutation in the MTase catalytic site and the SAM binding site;
 wherein the at least one mutation in the MTase catalytic site is in at least one of the K-D-K-E tetrad sites and the at least one mutation in the SAM binding site is in the G×G×G . . . D/E/W site; and,   wherein the paramyxovirus is human metapneumovirus (hMPV) and the at least one K-D-K-E tetrad site mutation is at least one of rhMPV-K1673A, rhMPV-D1779A, rhMPV-K1817A, rhMPV-E1848A, and rhMPV-E1848Q and the at least one mutation in the G×G×G . . . D/E/W site is at least one of rhMPV-G1696A, rhMPV-G1698A, rhMPV-G1700A, and rhMPV-D1755A.   
     
     
         5 . The recombinant paramyxovirus composition of  claim 1 , which is a mammalian immunogen. 
     
     
         6 . The recombinant paramyxovirus composition of  claim 1 , which is a human immunogen. 
     
     
         7 . A method of eliciting an immune response in a mammal comprising: administering to the mammal a recombinant paramyxovirus composition of  claim 1 . 
     
     
         8 . The method according to  claim 7 , wherein the composition is administered orally. 
     
     
         9 . The method according to  claim 7 , wherein the composition is administered intranasally. 
     
     
         10 . A method of preparing a pharmaceutical composition for passive immunization of an individual in need of immunization comprising: mixing a paramyxovirus composition of  claim 1  with a suitable excipient or carrier, thereby forming a pharmaceutical composition. 
     
     
         11 . The method according to  claim 10 , wherein the pharmaceutical composition is formulated for oral administration. 
     
     
         12 . The method according to  claim 10 , wherein the pharmaceutical composition is formulated for intranasal administration. 
     
     
         13 . A composition  claim 1 , wherein the paramyxovirus virulence is attenuated or eliminated in any mammal susceptible to paramyxovirus.