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Tuberculosis vaccines comprising antigens expressed during the latent infection phase

A vaccine and antigen technology, applied in bacterial antigen components, antibacterial drugs, depsipeptides, etc., can solve problems such as non-specific protection of disease deterioration

Inactive Publication Date: 2008-08-20
STATENS SERUM INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However this vaccine only worked when administered as a DNA vaccine and proved controversial as other groups claimed that vaccination using this regimen induced non-specific protection and even exacerbated disease (Turner, 2000)

Method used

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  • Tuberculosis vaccines comprising antigens expressed during the latent infection phase
  • Tuberculosis vaccines comprising antigens expressed during the latent infection phase
  • Tuberculosis vaccines comprising antigens expressed during the latent infection phase

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0149] Human recognition of starvation-inducing antigens

[0150] Human recognition of Rv2660c was assessed in a cohort of pulmonary TB patients from Uganda provided by the WHO Tuberculosis Specimen Bank. Patients with negative and positive HIV infection characteristics were included (N=94 and N=73, respectively). The control group consisted of one hundred healthy Danish-resident donors with estimated BCG coverage greater than 90%.

[0151]Microtiter plates were coated with 1.0 μg / ml (100 μl per well) of Rv2660c protein and incubated with 100x diluted serum samples, developed using peroxidase-conjugated rabbit anti-human Ig and tetramethylbiphenyl as substrates (results in figure 1 shown in ).

[0152] in conclusion

[0153] In this study, the recognition of starvation-inducing proteins was tested. Based on the cutoff determined from the control group with a sensitivity of 97%, it was possible to confirm TB infection in 45% of HIV- cases and 61% of HIV+ cases. The experi...

Embodiment 2

[0155] Prevention of immunogenicity and reactivation of starvation-induced antigen (Rv2659c) by post-exposure administration

[0156] Mice were infected with M. tuberculosis and treated with antibiotics to reduce bacterial burden and entered a latent infection phase with bacterial burden close to detection levels. During the incubation period of infection, the mice were inoculated with Rv2659c-containing adjuvant (such as DDA / MPL) three times every two weeks. One week after the last inoculation, INF-γ secretion of blood cells stimulated with Rv2659c was analyzed by ELISA ( figure 2 ).

[0157] Ability of the starvation-inducible protein Rv2659c to induce protection against reactivation of Mycobacterium tuberculosis

[0158] Groups of mice with latent M. tuberculosis were inoculated subcutaneously three times every two weeks with Rv2659c formulated in an adjuvant such as DDA / MPL, according to relative to unvaccinated (latently infected) mice The protective efficacy was asse...

Embodiment 3

[0162] Immunogenicity and protection against aerosol Mycobacterium tuberculosis infection induced by the starvation-inducible antigen Rv2660c

[0163] Mice were inoculated three times with Rv2660c-containing adjuvant (such as DDA / MPL) every two weeks. One week after the last inoculation, INF-γ secretion after stimulation of blood cells with Rv2660c was analyzed by ELISA ( Figure 4 A). Three weeks after the final inoculation, splenocytes were used to measure IFN-γ secretion after stimulation by Rv2660c ( Figure 4 B), blood cells are used to measure antigen-specific proliferative responses ( Figure 4 C).

[0164] Groups of mice subcutaneously inoculated three times every two weeks with Rv2659c formulated in an adjuvant (such as DDA / MPL) were challenged with an aerosol infection containing M. The reduction in colony forming units (CFU) of the lung relative to uninoculated mice was assessed. Protection was assessed 12 weeks after vaccination. Rv2660c induced an approximat...

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Abstract

The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of the tuberculosis complex (M tuberculosis, M. bovis, M. africanum, M. microti). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from M. tuberculosis, the units of the fusion polypeptide being M. tuberculosis antigens. Further, the invention is related to the use of a vaccine comprising a fusion polypeptide sequence or nucleic acid sequence of the invention given at the same time as BCG, either mixed with BCG or administered separately at different sites or routes for preparing said immunogenic composition, vaccine, or pharmaceutical composition.

Description

technical field [0001] The present invention discloses a starvation-inducing antigen, or a novel fusion polypeptide based on an immunogenic polypeptide of a polypeptide derived from Mycobacterium tuberculosis induced during starvation, and one or more fusion polypeptides or starvation-inducing antigens of the present invention are used Use in the preparation of immunogenic compositions, vaccines or pharmaceutical compositions for administration to humans / animals, and such immunogenic compositions, vaccines or pharmaceutical compositions. Background technique [0002] Human tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), is a serious global health problem, causing about 3 million deaths per year, according to WHO. During the 1960s and 1970s, the incidence of new tuberculosis (TB) cases has declined worldwide, but in recent years, due in part to the advent of AIDS and the emergence of multidrug-resistant (multidrug) strains of Mycobacterium tuberculosis, ...

Claims

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Application Information

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IPC IPC(8): C07K14/35A61K39/04A61P31/06
Inventor 克劳斯·奥高卡里纳·温斯波－伦德贝里彼得·安德森
Owner STATENS SERUM INST
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