Pneumococcal vaccine and uses thereof

Abstract

The present invention relates to new pneumococcal vaccines. The invention also relates to vaccination of subjects, in particular immunocompromised subjects, against pneumococcal infections using said novel pneumococcal vaccines.

Description

FIELD OF THE INVENTION[0001]The present invention relates to new pneumococcal vaccines. The invention also relates to vaccination of subjects, in particular immunocompromised subjects, against pneumococcal infections using said novel pneumococcal vaccines.BACKGROUND OF THE INVENTION[0002]Pneumococcal diseases are a major public health problem all over the world. Infections caused by pneumococci are a major cause of morbidity and mortality all over the world. Pneumonia, febrile bacteraemia and meningitis are the most common manifestations of invasive pneumococcal disease, whereas bacterial spread within the respiratory tract may result in middle-ear infection, sinusitis or recurrent bronchitis. Compared with invasive disease, the non-invasive manifestations are usually less severe, but considerably more common.[0003]In spite of the importance of pneumococcal disease, there is a scarcity of information on disease burden, particularly from developing countries. This is partly due to th...

AI Technical Summary

Benefits of technology

[0037]N is a B cell neutralizing sequence that begins with a CGG trinucleotide and is at least 10 nucleotides long. A B cell neutralizing motif includes at least one CpG sequence in which the CG is preceded by a C or followed by a G (Krieg A M et al. (1998) Proc Natl Acad Sd USA 95:12631-12636) or is a CG containing DNA sequence in which the C of the CG is methylated. Neutralizing motifs or sequences have some degree of immunostimulatory capability when present in an otherwise non-stimulatory motif, but when present in the context of other immunostimulatory motifs serve to reduce the immunostimulatory potential of the other motifs.

[0064]In an embodiment, all the internucleotide linkage of the CpG oligonucleotides disclosed herein are phosphodiester bonds (“soft” oligonucleotides, as described in the PCT application WO2007 / 026190). In another embodiment, CpG oligonucleotides of the invention are rendered resistant to degradation (e.g., are stabilized). A “stabilized oligonucleotide” refers to an oligonucleotide that is relatively resistant to in vivo degradation (e.g. via an exo- or endo-nuclease). Nucleic acid stabilization can be accomplished via backbone modifications. Oligonucleotides having phosphorothioate linkages provide maximal activity and protect the oligonucleotide from degradation by intracellular exo- and endo-nucleases.

[0185]In a particular embodiment of the present invention, the immunocompromised subject to be vaccinated is taking a drug or treatment that lowers the body's resistance to infection.

[0196]In a particular embodiment of the present invention, the immunocompromised subject to be vaccinated suffers from neutropenia. In a particular embodiment of the present invention, the immunocompromised subject to be vaccinated has a neutrophil count below 2×109 cells per liter, or below 1×109 cells per liter, or below 0.5×109 cells per liter, or below 0.1×109 cells per liter, or below 0.05×109 cells per liter. A low white blood cell count or “neutropenia” is a condition characterized by abnormally low levels of neutrophils in the circulating blood. Neutrophils are a specific kind of white blood cell that help prevent and fight infections. The most common reason that cancer patients experience neutropenia is as a side effect of chemotherapy. Chemotherapy-induced neutropenia increases a patient's risk of infection and disrupts cancer treatment.

[0204]As shown in the example part, some of the shortcomings of current vaccination can be overcome using the vaccine of the invention. In particular the vaccine of the invention may reduce the number of vaccinations required to achieve seroprotection, accelerate seroconversion, possibly permitting post-exposure vaccination, reduce the proportion of non-responders, reduce the amount of antigen required, increase antibody avidity and protective activity and / or lead to a more sustained antibody levels.

Problems solved by technology

Pneumococcal diseases are a major public health problem all over the world.

Infections caused by pneumococci are a major cause of morbidity and mortality all over the world.

In spite of the importance of pneumococcal disease, there is a scarcity of information on disease burden, particularly from developing countries.

This is partly due to the inherent problem of obtaining an etiological diagnosis in cases of pneumonia.

However, based on available data, acute respiratory infections kill an estimated 2.6 million children under five years of age annually.

Pneumococcal resistance to essential antimicrobials such as penicillins, cephalosporins and macrolides is a serious and rapidly increasing problem worldwide.

Some of the shortcomings of current vaccination include: need for several boosts to achieve protection, delay in rise of protective antibodies, prevalence of vaccine non-responders (this is particularly a problem for immune-compromised individuals), cost of antigen and vaccine production which is a very significant limitation in the development of new conjugated pneumococcal vaccines, poorly protective antibodies with low affinity, falling antibody titres over time.

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