Vaccine against streptococcus pneumoniae capsular polysaccharides

Abstract

The present invention relates to the field of bacterial polysaccharide antigen vaccines. In particular, the present invention relates to specific advantageous pnumococcal polysaccharide conjugates adjuvanted with 3D-MPL and substantially devoid aluminium-based adjuvant.

Description

[0001] The present invention relates to bacterial polysaccharide antigen vaccines, their manufacture and the use of such polysaccharides in medicines.[0002] In particular the present invention relates to three inter-related aspects: A--vaccines comprising a pneumococcal polysaccharide antigen, typically a pneumococcal polysaccharide conjugate antigen, formulated with a protein antigen from Streptococcus pneumoniae and optionally a Th1 inducing adjuvant; B--specific, advantageous pneumococcal polysaccharide conjugates adjuvanted with a Th1 adjuvant; and C--bacterial polysaccharide conjugates in general conjugated to protein D from H. influenzae.BACKGROUND OF INVENTION[0003] Streptococcus pneumoniae is a Gram-positive bacteria responsible for considerable morbidity and mortality (particularly in the young and aged), causing invasive diseases such as pneumonia, bacteremia and meningitis, and diseases associated with colonisation, such as acute Otitis media. The rate of pneumococcal pne...

AI Technical Summary

Problems solved by technology

The latter three vaccines confer protection against bacteria causing respiratory infections resulting in severe morbidity and mortality in infants, yet these vaccines have not been licensed for use in children less than two years of age because they are inadequately immunogenic in this age group [Peltola et al.

The 23-valent vaccine does not demonstrate protection against pneumococcal pneumonia (in certain high risk groups such as the elderly) and otitis media diseases.

Many are very efficient, but cause significant local and systemic adverse reactions that preclude their use in human vaccine compositions.

The practicality of using an immunization scheme that requires a delay in the administration of MPL relative to antigen, especially in infants, is questionable.

Amongst the problems associated with the polysaccharide approach to vaccination, is the fact that polysaccharides per se are poor immunogens.

Problems Associated with Commonly-Used Carriers

A number of problems are associated with each of these commonly used carriers, including in production of GMP conjugates and also in immunological characteristics of the conjugates.

In addition, for vaccines which require regular boosting, the use of highly immunogenic carriers such as TT and DT are likely to suppress the polysaccharide antibody response after several injections.

These multiple vaccinations may also be accompanied by undesirable reactions such as delayed type hyperresponsiveness (DTH).

This is particularly so in combination vaccines, where epitope suppression is especially problematic if the same carrier is used for various polysaccharide antigens.

Pneumococcal polysaccharide vaccines (conjugated or not) may not be able to protect against pneumonia in the elderly population for which the incidence of this disease is very high.

Antibody responses may also be impaired in the elderly.

Contrary to the normally accepted dogma, normal levels of anti-capsular polysaccharide antibodies may not be effective in complete clearance of bacteria, as pneumococci may invade host cells to evade this branch of the immune system.

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