Method for Inducing a Cell-Mediated Immune Response and Improved Parenteral Vaccine Formulations Thereof

a cell-mediated immune response and cell-mediated technology, applied in the field of vaccine formulations, can solve the problem of no general method for predicting or anticipating the nature of the immune response, and achieve the effect of protecting immunity against the infectious agen

Inactive Publication Date: 2006-12-28
MERRION RES III LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Review of the above cited references and other literature in the area shows that there is no general method for predicting or anticipating the nature of the immune response induced by an antigen in combination with a given adjuvant.

Method used

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  • Method for Inducing a Cell-Mediated Immune Response and Improved Parenteral Vaccine Formulations Thereof
  • Method for Inducing a Cell-Mediated Immune Response and Improved Parenteral Vaccine Formulations Thereof
  • Method for Inducing a Cell-Mediated Immune Response and Improved Parenteral Vaccine Formulations Thereof

Examples

Experimental program
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Effect test

example 1

Preparation of KLH−PLGA Microparticles Using a Solvent Evaporation Method

[0044] A polymer solution of PLGA [poly (D,L-lactide-co-glycolide), 50:50; i.v.=0.94 dl / g; supplied by Boehringer Ingelheim] in dichloromethane (10% PLGA in 10 ml DCM) was prepared two hours prior to use and subsequently chilled 30 minutes prior to use. The antigen, KLH (supplied by Calbiochem as a powder), was prepared as an aqueous solution (5.1 mg KLH in 1 ml water) containing 2% PVA. A first water-in-oil emulsion was prepared by adding the antigen solution to the polymer solution and homogenising for 1 min. at 24,000 rpm on ice. This first emulsion was poured slowly into an aqueous solution of PVA (40 ml, 3% PVA) forming a second water-oil-water emulsion and homogenisation was continued for 2 min. with a 15 sec. break [1 min.; 15 sec. break; 1 min.]. The resulting emulsion was stirred for 2 hours to evaporate the dichloromethane. The antigen-loaded particles (75% yield) were collected by centrifugation (10...

example 2

Preparation of PTd−PLGA Microparticles Using a Solvent Evaporation Method

[0051] Using a method substantially the same as that described in Example 1 above, PTd (supplied by Katetsuken) loaded PLGA particles were prepared. The polymer solution was 6.7% PLGA in 15 ml DCM and the antigen solution was 744 μg PTd in 2 ml water containing 0.9% PVA. The first water-in-oil emulsion was poured into 80 ml aqueous PVA (3% PVA) to form the water-oil-water emulsion. The emulsion was left over night to evaporate the DCM. After collection (88% yield), the microparticles were washed with chilled autoclaved water (30 ml).

[0052] Characterisation of these particles, identified as PTd-1 in Table 1 below, showed that the microparticles formed were smooth and spherical in appearance with at least 50% of the particles less than 5 microns in diameter. Laser light diffractometry showed that the particles had a D50% of 2.5 μm. The microparticles were loaded with antigen at 0.12 μg / mg, representing an entra...

example 3

Preparation of FHA−PLGA Microparticles Using a Solvent Evaporation Method

[0055] A procedure substantially similar to that used in Example 2 was employed for the preparation of FHA-loaded PLGA microparticles. Two batches of FHA−PLGA microparticles were prepared. For these two batches (FHA-1 and FHA-2 in Table 2 below) the polymer solution was 4% PLGA in 20 ml DCM and the antigen solution was 0.87 μg FHA in 2 ml water containing no PVA. The first water-in-oil emulsion was poured into 80 ml aqueous PVA (3% PVA) to form the water-oil-water emulsion. The characteristics of these two batches are given in Table 2 below. FHA-1 and FHA-2 were pooled (the pooled microparticles are labelled FHA-3 in Table 2) for antigen release determination and i.p. protection studies (see Example 7 below). SEM analysis showed the FHA-1 and FHA-2 microparticles to be smooth and spherical in nature with at least 50% of the particles less than 5 microns in diameter.

TABLE 2ExampleLoadingD50%No.(mg / mg)% EE(μm)...

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Abstract

A method of inducing either a TH1 polarised immune response, a TH2 polarised immune response or a combined TH1 and TH2 response to an antigen and associated vaccine formulations are disclosed. A method is provided for inducing a polarised TH1 response by parenteral administration of microparticles sized such that at least 50% of the microparticles are less than 5 μm, the microparticles containing antigen entrapped or encapsulated by a biodegradable polymer. Additionally, a method is provided for inducing a polarised TH2 response by parenteral administration of nanoparticles sized such that at least 50% of the nanoparticles are less than 600 nm, the nanoparticles containing antigen entrapped or encapsulated by a biodegradable polymer. Vaccine formulations containing the B. pertussis antigens PTd, FHA or a combination of PTd and FHA are provided.

Description

FIELD OF THE INVENTION [0001] The present invention relates to vaccine formulations and to methods for inducing an immune response that is polarised in favour of either a cell-mediated TH1 immune response, a humoral TH2 immune response or a combined TH1 and TH2 response. In particular, the present invention relates to parenteral microparticulate and nanoparticulate vaccine formulations comprising antigens entrapped or encapsulated within polymer particles. DESCRIPTION OF THE PRIOR ART [0002] Controlled release antigen delivery systems have attracted considerable interest in the continuing search for vaccine carriers. The effectiveness of polymer matrices in the sustained release of antigen was first demonstrated in 1979 with the entrapment of bovine serum albumin in a non-degradable ethylene-vinyl acetate copolymer pellet for subcutaneous implantation [Preis et al, J. Immunol. Methods 28, 193-197 (1979)]. This composition induced an antibody response for six months after administrat...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/10A61K9/50A61K9/16
CPCA61K9/0019A61K9/0024A61K9/1647Y10S530/825A61K2039/55555A61K2039/57A61K39/099
Inventor BRAYDEN, DAVID J.
Owner MERRION RES III LTD
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