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Double-chain RNA and method for initiate, enhance or adjust immunomodulatory of immune response

A technology of antigen and composition, applied in the field of non-coding RNA motifs

Inactive Publication Date: 2008-03-26
MULTICELL IMMUNOTHERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The mechanism also reveals distinct strategies for the immune system to distinguish self and nonself antigens, previously thought to be determined only at the level of the antigen-receptor repertoire

Method used

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  • Double-chain RNA and method for initiate, enhance or adjust immunomodulatory of immune response
  • Double-chain RNA and method for initiate, enhance or adjust immunomodulatory of immune response
  • Double-chain RNA and method for initiate, enhance or adjust immunomodulatory of immune response

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Experimental program
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Embodiment approach

[0007] Various embodiments of the invention include:

[0008] CLAIMS 1. A method of enhancing an immune response to an antigen comprising administering a composition consisting of double-stranded RNA and co-administering said composition with said antigen.

[0009] 2. A method of enhancing or modulating an immune response to an antigen, when said antigen is already present in the body, comprising administering a composition consisting of double stranded RNA.

[0010] 3. The method of paragraph 1, wherein the RNA is a non-coding RNA.

[0011] 4. The method of paragraph 1 or 2, wherein the double-stranded RNA consists of polyadenine and polyuracil.

[0012] 5. The method of paragraph 1 or 2, wherein the double-stranded RNA consists of one of polyguanine and polycytosine or polyinosine and polycytosine.

[0013] 6. The method of paragraph 1 or 2, wherein the double-stranded RNA consists of adenine and uracil.

[0014] 7. The method of paragraph 1 or 2, wherein the double-stran...

Embodiment 1

[0195] Example 1: Effects of Various Mergers of RNA Motifs on Antibody Responses to Standard Antigens (OVA)

[0196] The effect of various RNA pools (Table 1 ) on adaptive immunity was determined in C57B1 / 6 mice co-immunized with OVA via the airway. As described in the "Materials and Methods" section, the antibody responses were expressed as mean ± SEM of IgG endpoint titers (n=4 / group). As controls, OVA in sterile PBS, OVA with cholera toxin subunit B (CTB) and PBS alone were used, respectively. As shown in Figure 1A, the pool of dsRNAs corresponding to the greatest impact on the antibody response had significantly enhanced specific immunity. In addition, pools of single-stranded species that are complementary to each other reproduce this enhancement.

[0197] This suggests that both the residue nature and the secondary structure of RNAs determine their ability to function as "danger" motifs, influencing specific B cell responses.

Embodiment 2

[0198] Example 2: Effect of various individual dsRNA motifs on induction of antibody responses against OVA

[0199]Experiments were performed as described in the previous examples and in the "Materials and Methods" section, however, instead of using pools of RNAs, we used individual dsRNAs. The results are shown in Figure 1B in the same manner as Figure 1A. The results are representative of two independent experiments. Inset: ratio of mean IgG2a and IgG1 titers to OVA. The order from left to right is similar to the main figure: PBS OVA, CTB OVA, pC:pG OVA, pI:pC OVA and pA:pU OVA. In the second round of screening shown in Figure 1B, two types of motifs constituting double-stranded RNA, pA:pU and pI:pC, were confirmed to contribute to the generation of IgG responses against specific antigens in C57BL / 6 mice have a noticeable impact. Similar results were obtained in TLR4- / -C3H / HeJ mice with impaired responses to endotoxin (not shown).

[0200] Thus, individual RNA motifs ex...

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Abstract

The present application is directed to non-coding RNA motifs that are used in conjunction with an antigen or without an antigen to induce, enhance or modulate an immune response that comprises a B cell and a T cell component.

Description

field of invention [0001] The present invention generally relates to motifs useful for inducing an immune response. In particular, the application relates to non-coding RNA motifs that are used to induce, enhance or modulate an immune response including B cell (antibody) and optionally T cell components, with or without combination with an antigen. Background of the invention [0002] A large number of viral infections are associated with, or lead to their production, RNA species not normally encountered under normal conditions. Said RNAs are genomic segments (in the case of viruses containing double-stranded RNAs), replicative intermediates or stem-loop-structures, which are recognized by innate immune receptors such as Toll-like receptor 3 (TLR3), And induce the production of IFN-I and other soluble mediators. In addition, certain dsRNA motifs, such as polyI:polyC (pI:pC or pI:C), have been shown to activate immature dendritic cells to a stage where they can function as ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H21/04A61K48/00
Inventor A·I·博特王立林L·德拉玛丽D·史密斯B·菲利普斯
Owner MULTICELL IMMUNOTHERAPEUTICS
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