Vaccine Compositions Comprising a Saponin Adjuvant

a technology of adjuvant and vaccine, which is applied in the direction of dsdna viruses, immunological disorders, antibody medical ingredients, etc., can solve the problems of high toxicity of these molecules, preventing their use in vaccine formulations and affecting the quality of life of patients

Inactive Publication Date: 2008-11-13
GLAXOSMITHKLINE BIOLOGICALS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0060]Other aspects and advantages of the present invention are described further in the following detailed description of the preferred embodiments thereof.

Problems solved by technology

Both LPS and lipid A have long been known for their strong adjuvant effects, but the high toxicity of these molecules has precluded their use in vaccine formulations.
Influenza results in an economic burden, morbidity and even mortality, which are significant.
Individuals with underlying chronic diseases are also most likely to experience such complications.
Young infants also may suffer severe disease.
However, there is little evidence that current influenza vaccines work in small children under two years of age.
However, in a later publication, the same vaccine has not demonstrated its improved profile compared to a non-adjuvanted split vaccine (Puig-Barbera et al., 2004, Vaccine 23, 283-289).
The elderly or those with underlying chronic diseases are most likely to experience such complications, but young infants also may suffer severe disease.
This can result in virus escaping ‘herd immunity’ and establishing pandemics.
If such viruses have the potential to spread from person to person, they may spread worldwide within a few months to a year, resulting in a pandemic.
Such benign tumours may be distressing for the individuals concerned but tend not to be life threatening, with a few exceptions.

Method used

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  • Vaccine Compositions Comprising a Saponin Adjuvant
  • Vaccine Compositions Comprising a Saponin Adjuvant
  • Vaccine Compositions Comprising a Saponin Adjuvant

Examples

Experimental program
Comparison scheme
Effect test

example i

Immunological Read-Out Methods

I.1. Mice Methods

I.1.1. Hemagglutination Inhibition Test

Test Procedure

[0323]Anti-Hemagglutinin antibody titers to the three influenza virus strains were determined using the hemagglutination inhibition test (HI). The principle of the HI test is based on the ability of specific anti-influenza antibodies to inhibit hemagglutination of chicken red blood cells (RBC) by influenza virus hemagglutinin (HA). Heat inactivated sera were previously treated by Kaolin and chicken RBC to remove non-specific inhibitors. After pretreatment, two-fold dilutions of sera were incubated with 4 hemagglutination units of each influenza strain. Chicken red blood cells were then added and the inhibition of agglutination was scored. The titers were expressed as the reciprocal of the highest dilution of serum that completely inhibited hemagglutination. As the first dilution of sera was 1:20, an undetectable level was scored as a titer equal to 10.

Statistical Analysis

[0324]Statist...

example ii

Preparation of the MPL / QS21 Liposomal Adjuvant

II.3 Preparation of MPL Liquid Suspension

[0383]The MPL (as used throughout the document it is an abbreviation for 3D-MPL, i.e. 3-O-deacylated monophosphoryl lipid A) liquid bulk is prepared from 3D-MPL lyophilized powder. MPL liquid bulk is a stable concentrated (around 1 mg / ml) aqueous dispersion of the raw material, which is ready-to-use for vaccine or adjuvant formulation. A schematic representation of the preparation process is given in FIG. 1.

[0384]For a maximum batch size of 12 g, MPL liquid bulk preparation is carried over in sterile glass containers. The dispersion of MPL consists of the following steps:[0385]suspend the MPL powder in water for injection[0386]desaggregate any big aggregates by heating (thermal treatment)[0387]reduce the particle size between 100 nm and 200 nm by microfluidization[0388]prefilter the preparation on a Sartoclean Pre-filter unit, 0.8 / 0.65 μm[0389]sterile filter the preparation at room temperature (Sa...

example iii

Pre-Clinical Evaluation of Adjuvanted and Unadjuvanted Influenza Vaccines in Ferrets

III.1. Rationale and Objectives

[0398]Influenza infection in the ferret model closely mimics human influenza, with regards both to the sensitivity to infection and the clinical response.

[0399]The ferret is extremely sensitive to infection with both influenza A and B viruses without prior adaptation of viral strains. Therefore, it provides an excellent model system for studies of protection conferred by administered influenza vaccines.

[0400]This study investigated the efficacy of various Trivalent Split vaccines, adjuvanted or not, to reduce disease symptoms (body temperature) and viral shedding in nasal secretions of ferrets challenged with homologous strains.

[0401]The objective of this experiment was to demonstrate the efficacy of an adjuvanted influenza vaccine compared to the plain (un-adjuvanted) vaccine.

[0402]The end-points were:

1) Primary end-point: reduction of viral shedding in nasal washes af...

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Abstract

An immunogenic composition in a dose volume suitable for human use comprising an antigen or antigenic preparation, in combination with an adjuvant which adjuvant comprises an immunologically active saponin fraction derived from the bark of Quillaja Saponaria Molina presented in the form of a liposome and a lipopolysaccharide wherein said saponin fraction and said lipopolysaccharide are both present in said human dose at a level of below 30 μg.

Description

TECHNICAL FIELD[0001]The present invention relates to improved vaccine compositions, methods for making them, and their use in medicine. In particular the invention relates to adjuvanted vaccine compositions wherein the adjuvant is a liposomal formulation, comprising a saponin and a lipopolysaccharide. The present invention further relates to influenza vaccine formulations and vaccination regimes for immunizing against influenza disease.TECHNICAL BACKGROUND[0002]New compositions or vaccines with an improved immunogenicity are always needed. As one strategy, adjuvants have been used to try and improve the immune response raised to any given antigen.[0003]Lipopolysaccharides (LPS) are the major surface molecule of, and occur exclusively in, the external leaflet of the outer membrane of gram-negative bacteria. LPS impede destruction of bacteria by serum complements and phagocytic cells, and are involved in adherence for colonisation. LPS are a group of structurally related complex mole...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/127A61K39/00A61K39/25A61K39/09A61K39/015A61K39/145A61K39/12
CPCA61K39/00C12N2760/20034A61K39/145A61K2039/55555A61K2039/55572A61K2039/55577C12N2760/16134C12N2760/16234A61K39/015A61K39/092A61K39/39A61K2039/5258A61K2039/545A61K2039/55A61K2039/55505A61K2039/57A61K2039/6037A61K2039/70C12N2710/16134C12N2710/16734C12N2730/10134A61K39/12A61K2039/6068C12N2710/16771C12N2760/16171C12N2710/16171C12N2710/20071C12N2760/16271A61P15/00A61P31/04A61P31/12A61P31/16A61P31/18A61P31/20A61P31/22A61P33/06A61P35/00A61P37/00A61P37/04A61P43/00Y02A50/30A61K39/102A61K39/1045C12N2710/10134
Inventor VANDEPAPELIERE, PIERRE
Owner GLAXOSMITHKLINE BIOLOGICALS SA
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