CMV Glycoproteins and Recombinant Vectors

Abstract

Disclosed herein are recombinant CMV vectors which may comprise a heterologous antigen that can repeatedly infect an organism while inducing a CD8+ T cell response to immunodominant epitopes of the heterologous antigen. The CMV vector may comprise a deleterious mutation in the US11 glycoprotein or a homolog thereof.

1 . A cytomegalovirus (CMV) vector comprising:
 a first nucleic acid sequence encoding US2, US3, or US6 or a homolog thereof;   and a second nucleic acid sequence encoding an exogenous  Mycobacterium tuberculosis  antigen;   wherein the vector does not encode a functional US11 protein or homolog thereof.   
     
     
         2 . The vector of  claim 1 , wherein the first nucleic acid sequence encodes US2, US3, and US6. 
     
     
         3 . The vector of  claim 2 , wherein a nucleic acid encoding a US11 ORF is deleted. 
     
     
         4 . The vector of  claim 1 , further comprising a third nucleic acid sequence encoding US11 and wherein the nucleic acid sequence encoding US11 comprises a point mutation, a frameshift mutation, and/or a deletion of one or more nucleotides of the nucleic acid sequence encoding US11. 
     
     
         5 - 6 . (canceled) 
     
     
         7 . A method of eliciting an immune response to an antigen in a subject, the method comprising administering an effective amount of the vector of  claim 1 . 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 7 , wherein the subject was previously exposed to CMV. 
     
     
         10 . The method of  claim 11 , wherein the subject is a human or a rhesus macaque. 
     
     
         11 . The method of  claim 7 , wherein the CMV vector comprises one or more of a point mutation in a nucleic acid sequence encoding US11, a frameshift mutation in the nucleic acid sequence encoding US11, a deletion of all or part of the nucleic acid sequence encoding US11, or an antisense or RNAi construct that inhibits the expression of US11. 
     
     
         12 . The method of  claim 7 , wherein administering comprises intravenous, intramuscular, intraperitoneal, or oral administration of the CMV vector. 
     
     
         13 . The vector of  claim 1 , wherein the first nucleic acid sequence encodes a US2 comprising the amino acid sequence of SEQ ID NO: 1, a US3 comprising the amino acid sequence of SEQ ID NO: 2, or a US6 comprising the amino acid sequence of SEQ ID NO:3. 
     
     
         14 . The vector of  claim 1 , wherein the first nucleic acid sequence encodes a US2 comprising the amino acid sequence of SEQ ID NO: 1, a US3 comprising the amino acid sequence of SEQ ID NO:2, and a US6 comprising the amino acid sequence of SEQ ID NO: 3. 
     
     
         15 . The vector of  claim 1 , wherein the functional US11 protein comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         16 . The vector of  claim 2 , wherein the functional US11 protein comprises the amino acid sequence of SEQ ID NO:4. 
     
     
         17 . The vector of  claim 3 , wherein the functional US11 protein comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         18 . The vector of  claim 1 , wherein the vector does not encode a functional US8 or a functional US10 protein, or homolog thereof. 
     
     
         19 . The vector of  claim 18 , wherein the vector comprises a deletion of all of the nucleic acid sequence encoding US8-US11. 
     
     
         20 . The vector of  claim 1 , wherein the vector further comprises a promoter operably linked to the second nucleic acid sequence encoding an exogenous  Mycobacterium tuberculosis  antigen, wherein the promoter is a constitutive promoter, an inducible promoter, a non-viral promoter, or a viral promoter.