Adjuvant combinations of liposomes and mycobacteriaial lipids for immunization compositions and vaccines

a technology of liposomes and mycobacteria, which is applied in the direction of antibacterial agents, antibacterial antigen ingredients, antibody medical ingredients, etc., can solve the problems of not always providing satisfactory resistance to human tb in every population, inducing a sufficient immune response to confer protection, and many highly purified substances are not very immunogenic. , to achieve the effect of synergistic adjuvant effect of dda and increased immune respons

Inactive Publication Date: 2006-12-21
AGGER ELSE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012] In the present invention it is demonstrated that a surprisingly high protective immune response is obtained when lipids extracted from M. bovis BCG are used as adjuvant together with the cationic surfactant. A greatly increased protective immune response is obtained when DDA is added to a total lipid extract of M. bovis BCG, compared to that obtained using either of the components alone, showing a synergistic adjuvant effect of DDA and the total lipid extract. The combination of DDA and total lipids extracted from M. bov

Problems solved by technology

However, although more than 3 billion doses of BCG have been administered (more than any other vaccine) (Bloom and Fine, 1994), it does not always provide satisfactory resistance to humans TB in every population.
Unfortunately, many highly purified substances are not very immunogenic and do not induce a sufficient immune response to confer protection.
A large number of adjuvants exist but most of these suffer from numerous problems that preclude their use in humans.
The only adjuvants accepted for human use are aluminum-based adjuvants (AlOH-salts) and MF-59, but they both induce Th2-biased responses, which makes

Method used

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  • Adjuvant combinations of liposomes and mycobacteriaial lipids for immunization compositions and vaccines
  • Adjuvant combinations of liposomes and mycobacteriaial lipids for immunization compositions and vaccines
  • Adjuvant combinations of liposomes and mycobacteriaial lipids for immunization compositions and vaccines

Examples

Experimental program
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Effect test

example 1

TLC of Total, Polar and Apolar Lipids from M. bovis BCG

[0092] The apolar lipids identified in the total extract were phthiocerol A dimycocerosate (A), phthiocerol C dimycocerosate (C), and a small amount of phthiocerol B dimycocerosate (B). Large amounts of triacylglycerol (TG) were also detected. These lipids were also detected in the apolar extract as expected. In the polar extract, only a trace of TG and a spot probably representing free fatty acids (FFA) were detected (FIG. 1).

[0093] The total and polar extract contained the following polar lipids: Phosphatidyinositol mannosides, probably triacylated (1) and tetracylated (2) pentamannosides, and triacylated (3) and tetracylated (4) dimannosides. Phosphatidylinositol (PI), phosphatidylethanolamine (PE) and diphosphatidylglycerol (cardiolipid, DPG) were major phospholipids. Small amounts of L-alpha-Phosphatidyl-DL-glycerol sodium salt (PG) and another phospholipid (7) were also present A glycolipid (8) was also observed in the ...

example 2

Use of Total Lipids from M. bovis BCG for Immunization of Mice

[0096] In this example studying the adjuvant activity of M. bovis BCG total lipids, mice were immunized with experimental vaccines consisting of 1 microgram of fusion protein Ag85B-ESAT6 emulsified in DDA adjuvanted with 100 μg of total lipids. Groups of mice receiving the Ag85B-ESAT6 alone, the Ag85B-ESAT6 and DDA alone, the Ag85B-ESAT6 in combination with the total lipids and a group of naïve mice was included as negative controls, while Ag85B-ESAT6 / DDA / TDB and a standard BCG vaccine were included as positive controls. This experiment was carried out using Th2 prone Balb / C mice (Peftoniemi et al, 2002), as only remarkably potent Th1-inducing adjuvants are capable of switching the immune response of this mouse strain in favour of a response characterized by production of Th1 cytokines such as IFN-gamma.

[0097] Five weeks after the first immunization, the IFN-gamma release was evaluated after in vitro re-stimulation of ...

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Abstract

The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldioctadecylammonium-bromide/chloride (DDA) and a lipid extract from The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from <The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis. The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis<The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis BCG The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis BCG <The present invention provides a vaccin adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis BCG. The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from <i>Mycobacterium bovis BCG<i>. <The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from <i>Mycobacterium bovis BCG<i>. The total lipid extract contains both apolar lipids, polar lipids, and lipids of intermediate polarity of which the apolar lipids were found to induce the most powerful immune responses. The total lipids may be extracted with chloroform/methanol and re-dissolved in water before the addition of surfactant. This preparation may be used to induce prominent cell-mediated immune responses in a mammal in order to combat pathogens, or as a treatment for cancer.

Description

FIELD OF INVENTION [0001] The present invention discloses an adjuvant comprising a surfactant and the total lipid extract of the BCG mycobacterium as well as the apolar fraction thereof and a vaccine comprising said adjuvant and an antigenic substance. BACKGROUND OF THE INVENTION [0002] The first vaccines consisted of live, attenuated pathogens. The attenuated forms were either naturally occurring closely related organisms or obtained through serial passages in culture. For example, tuberculosis (TB) in man has for many years been combated by vaccination with an attenuated strain of Mycobacterium bovis, the M. bovis BCG vaccine developed more than 80 years ago. However, although more than 3 billion doses of BCG have been administered (more than any other vaccine) (Bloom and Fine, 1994), it does not always provide satisfactory resistance to humans TB in every population. [0003] Today, a more up-to-date approach is to use highly purified substances, e.g. purified recombinant proteins....

Claims

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Application Information

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IPC IPC(8): A61K39/04A61P31/06
CPCA61K39/04A61K2039/55594A61K2039/55555A61P31/04A61P31/06A61P35/00A61P37/00A61P37/04A61P37/08G02B5/30
Inventor AGGER, ELSE
Owner AGGER ELSE
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