Methods and compositions for cytomegalovirus IL-10 protein
The present invention provides methods and compositions for treating and/or preventing a cytomegalovirus infection in a subject, comprising administering to the subject an effective amount of a cytomegalovirus interleukin-10 (IL-10) protein modified to have reduced functional activity while retaining immunogenicity. The present invention further provides nucleic acid molecules encoding a cytomegalovirus IL-10 protein or fragment thereof of this invention as well as vectors comprising such nucleic acids. Also provided herein are neutralizing antibodies that specifically bind cmvIL-10.
1. A cytomegalovirus IL-10 protein, wherein the protein comprises a substitution in one or more amino acids, wherein the substitution results in a phenotype of reduced binding to an interleukin-10 (IL-10) receptor protein and reduced functional activity as compared to a cytomegalovirus IL-10 protein lacking said substitution, and wherein the substitution is at K58, Q62, E160 and/or D162 in the amino acid sequence of SEQ ID NO:3, in any combination.
2. The cytomegalovirus IL-10 protein of claim 1 , wherein the substitution further results in a phenotype of retained immunogenicity as compared to a cytomegalovirus IL-10 protein lacking said substitution.
3. The cytomegalovirus IL-10 protein of claim 1 , wherein the substitution is K58E, Q62R, E160Q and/or D162H in the amino acid sequence of SEQ ID NO:3, in any combination.
4. The cytomegalovirus IL-10 protein of claim 1 , wherein the substitution is D162H and either Q62R or E160Q in the amino acid sequence of SEQ ID NO:3.
5. A composition comprising the cytomegalovirus IL-10 protein of claim 1 , in a pharmaceutically acceptable carrier.