Methods and compositions for modulating an immune response with immunogenic oligonucleotides
View Patent ↗This document relates to compositions and methods for modulating an immune response. For example, compositions of immunostimulatory CpG oligonucleotides derived from retroviral genomes are provided.
1. A method for stimulating lymphocyte cytokine production comprising contacting lymphocytes with an isolated nucleic acid consisting of from 20-84 contiguous nucleotides of a mammalian retroviral sequence, wherein said sequence comprises at least one CpG motif, with the proviso that at least one non-thymidine nucleotide 1, 2, or 3 bases immediately 5′ or immediately 3′ to said CpG motif is substituted with thymidine under conditions wherein said cytokine production is enhanced relative to uncontacted lymphocytes: wherein said nucleic acid consists of a sequence selected from the group consisting of SEQ ID NO: 30, 31, 34, 37, 40, 49, 51.
2. The method of claim 1 , wherein said nucleic acid is 20-50 nucleotides in length.
3. The method of claim 1 , wherein said nucleic acid is 24 nucleotides in length.
4. The method of claim 1 , wherein said mammalian retroviral sequence is a HIV genomic sequence.
5. The method of claim 1 , wherein said mammalian retroviral sequence is a SIV genomic sequence.
6. The method of claim 1 , wherein said contacted lymphocytes form primed lymphocytes.
7. The method of claim 1 , wherein said contacting further comprises application of a therapeutic antigen.
8. The method of claim 1 , wherein said stimulation is measured according to a TLR-9 antagonism assay.
9. The method of claim 1 , wherein said cytokine is selected from the group consisting of IL-6, IL-10, IL-12, and TNF-α, or any combination thereof.