Mutated parvovirus structural proteins as vaccines

Abstract

The present invention is related to a method for identifying a parvovirus mutated structural protein capable of specifically binding to a binder for an antigen, a parvovirus mutated structural protein which comprises at least one B-cell epitope heterologous to the parvovirus, a multimeric structure comprising the protein, a nucleic acid encoding the protein, a virus or cell comprising the protein, a method of preparing the protein, a medicament comprising the protein, nucleic acid or multimeric structure and its use.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 12 / 601,639, which has a 371 (c) date of Mar. 23, 2010, which is the U.S. National Stage of International Application No. PCT / EP2008 / 004366, filed Jun. 2, 2008, which claims the benefit of U.S. Patent Application No. 60 / 932,446, filed May 31, 2007, and European Patent Application No. 07013264.2, filed Jul. 6, 2007.BACKGROUND OF THE INVENTION[0002]The present invention is related to a method for identifying a parvovirus mutated structural protein capable of specifically binding to a binder for an antigen, a parvovirus mutated structural protein which comprises at least one B-cell epitope heterologous to the parvovirus, a multimeric structure comprising the protein, a nucleic acid encoding the protein, a virus or cell comprising the protein, a method of preparing the protein, a medicament comprising the protein, nucleic acid or multimeric structure and its use.[0003]Monoc...

AI Technical Summary

Benefits of technology

This patent describes how certain medications can stimulate the immune system to produce long-lasting antibodies against certain viral epitopes. These medications have a unique structure that can be easily screened and produced. The patent also describes a method for improving the affinity of the medication for its target protein by mutating the gene that encodes the protein. Overall, this patent provides a technical solution for efficiently screening and producing effective medications against viral infections.

Problems solved by technology

It can be observed that, if the concentration of a specific antibody with one particular idiotype is too high, the patient's immune system develops an antibody response against the idiotype of the therapeutic monoclonal antibody and thereby limits its efficacy.

In addition, antibodies to monoclonal therapeutic antibodies directed against other parts of the monoclonals often limit efficacy of a passive antibody therapy.

Therefore, many of the monoclonal antibody drugs need to be used in combination with the traditional immunosuppression regiments, increasing the overall treatment costs.

Furthermore, active suppression of the patient's immune system is detrimental especially, if an intact immune system is required to control the stage of disease such as for oncological indications.

Therefore, such treatments are expensive and inconvenient for the patients.

Additionally, anti-idiotype antibodies induce a polyclonal antibody response against the target antigen that hampers the potential mechanism for resistance to the treatment of e.g. in tumor cells.

However, anti-idiotypic antibody therapies face major disadvantages.

The titers of the induced polyclonal antibody response obtained by the vaccination with anti-idiotypic antibodies are often not high enough to establish a beneficial treatment.

This is due to the lack of a strong antigen as a vaccine, since antibodies per definition are not very immunogenic.

Furthermore, it is difficult to generate specific anti-idiotype vaccines because of this lack of immunogenicity and technical difficulties to identify anti-idiotypic antibodies.

However, it is questionable if epitopes linked by biotin or inserted by an educated guess can possibly induce the generation of auto-antibodies for a wide range of tolerogens, as advantageous epitopes for vaccination may be three-dimensional and inserted epitopes may refold due to the specific environment of the insertion site.

However, these attempts have been used only for fairly large pathogenic epitopes and not with tolerogens or small antigens or even individual epitopes, where B cell tolerance has to be broken to have a beneficial effect for the patient.

As a consequence, if an uncoupled library was used for a first screening against a target antibody, the chance that screened particles contained the genome coding for this specific peptide sequence might be very low.

However, even if 99% of free IgE were neutralized by the anti-IgE antibody, the therapy still would fail because the few remaining IgE molecules would be sufficient to sensitize the respective cells.

This results in cross-linking of receptor-bound IgE, causing an anaphylactic shock in animals treated systemically with such antibodies.

As outlined before, one disadvantage of passive immunization with a monoclonal antibody is the requirement of infusions every 2-4 weeks with relatively high antibody doses making such therapies expensive.

This would induce a systemic anaphylactic shock.

Although 33% of patients with CHD have low plasma levels of HDL-C as their primary lipid abnormality, there is currently no effective therapy for increasing the plasma concentration of HDL-C.

Diet and moderate exercise are ineffective, statins afford only a modest 5% to 7% increase in HDL-C, and niacin has side effects and compliance profiles that limit its use.

It commonly leads to significant disability and consequently to a significant reduction of quality of life.

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