Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide sequences

a technology of immunomodulatory polynucleotide sequence and respiratory virus, which is applied in the field of preventing and treating respiratory virus infection using immunomodulatory polynucleotide sequence, can solve the problems of significant loss of productivity annually, discomfort and even death of patients from respiratory virus infection, and the patient remains debilitated from infection, so as to reduce the incidence and/or severity

Inactive Publication Date: 2004-01-15
DYNAVAX TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

0022] We have discovered that immunostimulatory polynucleotide sequences (ISS) are effective anti-viral agents against respiratory viruses. A polynucleotide comprising an immunostimulatory sequence (an "ISS") is administered to an individual who is at risk of being exposed to respiratory virus, has been expos

Problems solved by technology

Despite massive research efforts to find cures, respiratory virus infection remains a major health problem worldwide.
Influenza and rhinovirus are causative agents for flu and common cold, respectively, lead to significant lost productivity annually as well as discomfort and even death due to illness.
While many over-the-counter remedies are available, these drugs merely treat symptoms, often with only limited success, leaving the patient still debilitated from the infecti

Method used

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  • Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide sequences
  • Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide sequences

Examples

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Effect test

example 1

Animal Model and Experimental Methods for Respiratory Viruses

[0119] Rat Model for RSV Infection and ISS Administration

[0120] Cotton rats, 50-100 g and 4-12 weeks old (Sigmoden hispidis) of either sex were used in these studies. All of the animals were descendants of two pair of cotton rats obtained in 1984 from the Small Animal Section of the Veterinary Research Branch, Division of Research Services, National Institutes of Health.

[0121] RSV strain A2 was purchased from the ATCC (ATCC VR26). Working stocks of this virus were prepared as described in detail by Wyde et al. (1995) Pediatr. Res. 38:543-550. ISS sequence tested for RSV experiments was 5'-TGACTGTGAACGTTCGAGATGA-3' (SEQ ID NO:1) (phosphorothioate). Control, non-ISS sequences used were 5'-TGACTGTGAAGGTTAGAGATGA-3' (SEQ ID NO:9) (phosphorothioate) and 5'-TCACTCTCTTCCTTACTCTTCT-3' (SEQ ID NO:10) (phosphorothioate), as well as PBS.

[0122] Assay for RSV Viral Titer

[0123] RSV levels in virus pools and lung lavage fluids (L.F.) wer...

example 2

Local Administration of ISS Reduces RSV Viral Titer

[0124] These experiments were performed to test the effect of local administration of ISS in terms of antiviral activity against respiratory syncytial virus (RSV) in cotton rats.

[0125] On day -3 (i.e., 3 days before infection with virus), 20 cotton rats (CRs) were selected and divided into five groups of four animals. The animals in Group 1 were lightly anesthetized and 50 .mu.L of phosphate buffered saline (PBS) was administered intranasally (IN). The CRs in Group 2 were similarly administered 150 .mu.g of ISS (5'-TGACTGTGAACGTTCGAGATGA-3') (SEQ ID NO:1), while the animals in Group 3 were similarly administered 150 .mu.g of control non-ISS sequence 5'-TGACTGTGAAGGTTAGAGATGA-3' (SEQ ID NO:9). Three days later, on Day 0, each of CRs in Group 4 were anesthetized and 150 .mu.g of ISS was administered IN, and the animals in Group 5 were administered, in a like manner, 150 .mu.g of control non-ISS sequence 5'-TGACTGTGAAGGTTAGAGATGA-3-' (...

example 3

Non-Local Administration of ISS and RSV Viral Titer

[0129] These experiments were performed to test the effect of non-local administration of ISS in terms of antiviral activity against RSV in cotton rats.

[0130] Twenty cotton rats were divided into 5 groups of 4 animals. Administered to these animals, either intraperitoneally (IP) or subcutaneously (SC), was PBS, immunostimulatory sequence (ISS) 5'-TGACTGTGAACGTTCGAGATGA-3' (SEQ ID NO:1) or non-ISS sequence 5'-TCACTCTCTTCCTTACTCTTCT-3' (SEQ ID NO:10), each sequence at 150 .mu.g / injection. On Day 0 each of these animals was inoculated IN with 100 TCID.sub.50 of RSV A2. Four days later each cotton rat was sacrificed. The lungs of each animal were removed, lavaged and assessed for RSV. The protocol is summarized in Table 3. The results from IP administration are shown in Table 4. The results from SC administration are shown in Table 5.

3TABLE 3 Protocol Dose ISS Day Day ISS given ISS RSV Day CRs Group admin. (.mu.g / CR) given given Sacrifi...

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Abstract

The invention provides methods of preventing and/or treating infection by a respiratory virus such as respiratory syncytial virus (RSV) and SARS-associated coronavirus, particularly reducing infection and/or one or more symptoms of respiratory virus infection. A polynucleotide comprising an immunostimulatory sequence (an "ISS") is administered to an individual which is at risk of being exposed to a respiratory virus, has been exposed to a respiratory virus or is infected with a respiratory virus. The ISS is administered without any antigens of the respiratory virus. Administration of the ISS results in reduced incidence and/or severity of one or more symptoms of respiratory virus infection.

Description

[0001] The present application is a continuation-in-part application of copending U.S. application Ser. No. 09 / 802,686, filed Mar. 9, 2001, which in turn claims the priority benefit of U.S. Provisional application No. 60 / 188,583, filed Mar. 10, 2000, each of which is hereby incorporated in their entirety by reference.[0002] The invention is in the field of immunostimulatory poynucleotides, more particularly their use in ameliorating or preventing respiratory viral infection and symptoms of respiratory viral infection.[0003] Despite massive research efforts to find cures, respiratory virus infection remains a major health problem worldwide. Influenza and rhinovirus are causative agents for flu and common cold, respectively, lead to significant lost productivity annually as well as discomfort and even death due to illness. While many over-the-counter remedies are available, these drugs merely treat symptoms, often with only limited success, leaving the patient still debilitated from t...

Claims

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Application Information

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IPC IPC(8): A61K31/7105C12N15/09A61K31/711A61K31/7115A61K39/39A61K48/00A61P31/14A61P31/16
CPCA61K31/7105A61K31/711A61K2039/55561A61K39/39A61K31/7115A61P31/12A61P31/14A61P31/16
Inventor VAN NEST, GARY
Owner DYNAVAX TECH CORP
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