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Novel live recombinant booster vaccine against tuberculosis

Inactive Publication Date: 2013-04-25
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a vaccine and method for preventing, reducing the possibility of or treating tuberculosis and leprosy in humans and animals that is more potent than current commercially available vaccines. This vaccine is easier and cheaper to manufacture than both virus-vectored vaccines and protein-in-adjuvant vaccines, and does not require purification. The vaccine can be grown in broth culture, without the need for purification. Overall, this patent is a technical improvement that has the potential to significantly impact the prevention and treatment of tuberculosis and leprosy.

Problems solved by technology

Current commercially available vaccines are of limited efficacy against pulmonary tuberculosis.

Method used

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  • Novel live recombinant booster vaccine against tuberculosis
  • Novel live recombinant booster vaccine against tuberculosis
  • Novel live recombinant booster vaccine against tuberculosis

Examples

Experimental program
Comparison scheme
Effect test

examples

Materials and Methods

[0042]A. BCG Strain (Wild-type M. bovis BCG Tice)

[0043]This strain was maintained in 7H9 medium pH 6.7 (Difco) at 37° C. in a 5% CO2-95% air atmosphere as unshaken cultures. Cultures were sonicated once or twice weekly for 5 min in a sonicating water bath to reduce bacterial clumping, as described (see, e.g. Horwitz, et al. (2000). “Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model.”Proc Natl Acad Sci USA 97(25): 13853-8).

B. Recombinant Attenuated Listeria monocytogenes Vaccines

1. rLm / Mtb30(01)

[0044]a. Construction of rLm / Mtb30(01)

[0045]rLm / Mtb30(01), an attenuated recombinant Listeria monocytogenes expressing the M. tuberculosis 30 kDa major secretory protein (Mtb30), was constructed using the attenuated L. monocytogenes host strain, LmΔactA, an L. monocytogenes str...

experiment 1

Immunogenicity of rLm / Mtb30 in Prime-Boost Vaccination Regimen

[0071]Specific-pathogen free 250-300 g outbred male Hartley strain guinea pigs from Charles River Breeding Laboratories, in groups of 6, were immunized intradermally as follows:[0072]Group A: Sham[0073]Group B: BCG Tice Parental Control (103 CFU) at Week 0[0074]Group C: BCG Tice Parental Control (103 CFU) at Week 0 and 100 μg of r30 in SAF adjuvant at Week 4[0075]Group D: BCG Tice Parental Control (103 CFU) at Week 0 and rAd / Mtb30 at Week 4[0076]Group E: BCG Tice Parental Control (103 CFU) at Week 0 and Lm Empty Vector at Week 4[0077]Group F: BCG Tice Parental Control (103 CFU) at Week 0 and rLm / Mtb30 at Week 4[0078]Group G: BCG Tice Parental Control (103 CFU) at Week 0 and rLm / Mtb30 C-0 at Week 4

[0079]At week 8, animals were tested for cutaneous delayed-type hypersensitivity (c-DTH) to r30, and after the skin test was assessed, the animals were euthanized for assay of splenic lymphocyte proliferation and antibody respons...

experiment 2

Protective Efficacy of rLm / Mtb30 in a Prime-Boost Vaccination Regimen in Guinea Pigs

[0087]Specific-pathogen free 250-300 g outbred male Hartley strain guinea pigs from Charles River Breeding Laboratories, in groups of 15 (except for the sham group, which had 9 animals), were immunized intradermally as follows:[0088]Group A: Sham[0089]Group B: BCG Tice Parental Control (105 CFU) at Week 0[0090]Group C: BCG Tice Parental Control (105 CFU) at Week 0 and 100 μg of r30 in SAF adjuvant at Week 4[0091]Group D: BCG Tice Parental Control (105 CFU) at Week 0 and 100 μg of r30 in SAF adjuvant at Weeks 4 and 8[0092]Group E: BCG Tice Parental Control (105 CFU) at Week 0 and rAd / Mtb30 at Week 4[0093]Group F: BCG Tice Parental Control (105 CFU) at Week 0 and rAd / Mtb30 at Weeks 4 and 8[0094]Group G: BCG Tice Parental Control (105 CFU) at Week 0 and rLm / Mtb30 at Week 4[0095]Group H: BCG Tice Parental Control (105 CFU) at Week 0 and rLm / Mtb30 at Weeks 4 and 8

[0096]Twenty weeks after immunization, all...

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Abstract

Embodiments of the invention comprise an improved vaccine for generating an immune response and preventing or treating mycobacterial diseases such as tuberculosis in humans and animals. Embodiments of the invention also comprise a method for using the vaccine against such mycobacterial diseases.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. provisional patent application No. 61 / 355,052, filed Jun. 15, 2010, the entire contents of which are incorporated herein by reference.STATEMENT OF GOVERNMENT SUPPORT[0002]This invention was made with Government support of Grant No. AI031338 awarded by the National Institutes of Health. The U.S. government has certain rights in this invention.1. FIELD OF THE INVENTION[0003]The present invention relates to methods and compositions of matter that are useful for preventing or reducing the possibility of infection caused by Mycobacterium tuberculosis, the agent of tuberculosis, and infection by other pathogenic strains of mycobacteria in humans and / or animals including Mycobacterium bovis and Mycobacterium leprae. 2. BACKGROUND[0004]Around the world, intracellular bacteria are responsible for millions of deaths each year and untold suffering. Tuberculosis, caused by Mycobacterium tuberculosis, is a l...

Claims

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Application Information

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IPC IPC(8): A61K39/04
CPCA61K39/04A61K2039/522A61K2039/523A61K2039/545A61K2039/5555A61K2039/55566C07K14/195C07K14/35C07K2319/40C12N1/20C12N1/36A61K39/02A61K2039/6037A61P31/00A61P31/10
Inventor HORWITZ, MARCUS A.JIA, QINGMEI
Owner RGT UNIV OF CALIFORNIA
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