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Immunogenic compositions comprising silicified virus and methods of use

A technology of immunogenicity and composition, which is applied in the field of immunogenic composition containing silicified virus and its use, and can solve problems such as the ability of immune response that is not yet known

Active Publication Date: 2015-11-04
PORTLAND STATE UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, prior to this disclosure, it was not known whether viruses encapsulated in silica retained infectivity or the ability to induce an immune response in an infected host

Method used

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  • Immunogenic compositions comprising silicified virus and methods of use
  • Immunogenic compositions comprising silicified virus and methods of use
  • Immunogenic compositions comprising silicified virus and methods of use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1: Inactivation, reactivation and desiccation tolerance of silicified viruses

[0115]This example describes the discovery that a variety of viruses can be reversibly inactivated by siliconization and, in some cases, that siliconization increases virus tolerance to desiccation. In the studies described below, the effect of silicification on viral infectivity and dryness tolerance was determined for four exemplary viruses: two bacteriophages (T4 and PRD1), one enveloped animal virus (vaccinia) and one Virus of Hyperthermophilic Archaea (SSV-K) (Wiedenheft et al., J Virol 78:1954, 2004).

[0116] introduction

[0117] A major disagreement in viral ecology is whether viral species are cosmopolitan (Breitbart and Rohwer, Trends Microbiol 13:278, 2005) or exhibit regional endemism. Studies of viruses in environments as diverse as volcanic hot springs, Arctic ice pools, and the open ocean have yielded conflicting results (Angly et al., PLOS Biology 4:2121, 2006). S...

Embodiment 2

[0138] Example 2: Immune response following administration of siliconized and non-siliconized VACV

[0139] This example describes the discovery that, following in vivo administration, silicified viruses are capable of inducing a virus-specific immune response.

[0140] In order to determine whether silicified virus can infect animal hosts and induce immune responses in animal hosts, C57BL / 6 mice were inoculated with 1 × 10 6 pfu of siliconized VV-OVA or non-silicified VV-OVA (recombinant vaccinia virus expressing ovalbumin) was administered. Antigen-specific T cells were measured by intracellular cytokine staining (ICS) and MHC tetramer staining seven days after the primary vaccination and five days after the booster vaccination ( figure 2 ).

[0141] Tetramer staining and ICS were performed to assess the frequency and number of viral antigen-specific T cells obtained from the spleens of vaccinated animals. MHC tetramers specific for VACV B8R peptide epitopes were used to...

Embodiment 3

[0144] Example 3: Silicification of bacteriophage PhiX174 as a parvovirus model

[0145] This example describes the discovery that siliconization can significantly reduce the infectivity of very small viruses.

[0146] In this study, two similar silicidation processes were compared - using the SLIDE-A-LYZER TM MINI dialysis units (10K MWCO, 0.5 mL units; Thermo-Fisher Cat. No. 88401 ) were subjected to siliconization, and the standard siliconization procedure described in Example 1. The procedures are the same except for the device used for dialysis. Very similar results were obtained using both schemes.

[0147] Phage PhiX174 is a very small (approximately 30 nm in diameter) non-enveloped virus that serves as a model virus for picornaviruses such as poliovirus, hepatitis A virus, rhinovirus, and foot-and-mouth disease virus, which also As model viruses of parvoviruses such as adeno-associated virus (AAV), murine parvovirus and canine parvovirus.

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Abstract

It is disclosed herein that viruses coated in silica retain infectivity and the capacity to induce an immune response in an infected host. In addition, silicifled virus is remarkably resistant to desiccation. Provided herein are methods of inducing a virus-specific immune response in a subject by administering to the subject an effective amount of silicified virus or silicified virus particles. Methods of enhancing a virus-specific cell-mediated immune response (such as aT cell-mediated immune response) in a subject by administering to the subject a silicified virus or silicified virus particles are also described herein. Further provided are immunogenic compositions comprising silicified virus or silicified virus particles, such as compositions useful as vaccines. The immunogenic compositions include a pharmaceutically acceptable carrier and / or an adjuvant.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 61 / 759,131, filed January 31, 2013, which is hereby incorporated by reference in its entirety. technical field [0003] The present disclosure relates to the preservation of viruses and related particles by encapsulating them in silica. The present disclosure also relates to immunogenic compositions comprising siliconized viruses or virus particles, and uses thereof for inducing or altering an immune response in a subject. [0004] Thanks for government support [0005] This invention was made with government support under Grant No. NNA11AC01G awarded by the National Aeronautics and Space Administration and DGE: 0114427 awarded by the National Science Foundation. The government has certain rights in this invention. Background technique [0006] The mechanisms of virus transmission, especially the endemicity of viruses of organisms in isolated "isl...

Claims

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Application Information

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IPC IPC(8): A61K39/12
CPCA61K39/12A61K2039/5252C12N2710/24134C12N2795/10134C12N2795/14034A61P31/12A61P37/04Y02A50/30A61K39/125A61K39/13A61K39/145A61K39/15A61K39/21A61K39/215A61K39/235A61K39/285A61K39/29A61K39/292A61K2039/525A61K2039/55505A61K2039/55561A61K2039/55566A61K2039/55588C12N7/00C12N2710/10021C12N2710/10034C12N2710/24121C12N2720/12321C12N2720/12334C12N2740/16021C12N2740/16034C12N2760/16021C12N2760/16034C12N2770/20021C12N2770/20034C12N2770/24021C12N2770/24034C12N2770/24221C12N2770/24234C12N2770/32421C12N2770/32434C12N2770/32621C12N2770/32634
Inventor K·M·斯泰德曼J·R·莱德勒K·巴亚特
Owner PORTLAND STATE UNIV