Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant virus encoding one or more heterologous proteins...
Reexamination Certificate
2002-01-09
2004-08-31
Mosher, Mary E. (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant virus encoding one or more heterologous proteins...
C424S093200, C424S207100, C424S208100, C514S04400A
Reexamination Certificate
active
06783762
ABSTRACT:
FIELD OF THE INVENTION
The invention lies in the field of medicine. More particularly the invention relates to vaccines, vaccine compositions and vaccination strategies for obtaining improved immune protection against infectious diseases.
BACKGROUND OF THE INVENTION
The ultimate goal of developing prophylactic and/or therapeutic vaccines for a large number of infectious agents has been difficult to achieve due to the inability to induce optimal immune responses to the pathogen in a safe and effective manner. The previously tried and proven approaches of vaccination with whole killed or live attenuated viruses are either unsafe or ineffective for the remaining infectious diseases of major public health concern. To avoid possible safety problems it has been possible to develop protein based vaccines consisting of one or several individual viral proteins or epitopes thereof. These are derived from individual viral genes expressed in vitro and purified as individual subunits in the protein in the absence of genetic material. Recombinant subunit vaccine approaches have proven effective for certain pathogens such as Hepatitis B. However, for many applications subunit antigens have been unsuccessful due to expression/production difficulties, alteration of relevant immunological epitopes or marked variability of the, pathogen requiring the continuous development, fermentation and purification of new antigens.
Recombinant live viral or bacterial vaccine vectors were developed as potential solutions to some of these problems. A replicating live virus or bacteria which does not cause disease has the potential to be used as a vector. Attenuated viruses such as adenovirus, poxvirus (i.e. vaccinia, MVA, canary or fowlpox) or bacteria such as
E. coli
, are being developed and evaluated as live vectors. Due to their ability to replicate (in some cases in a limited fashion) in a host without serious side effects, makes them candidate to carry and express foreign genes as “vaccine” antigens. Recombinant vaccines have the advantage that they replicate in the host and thereby induce stronger immune responses than whole killed viruses or bacteria or subunit proteins. An additional advantage is that an immune response to an antigen encoded by said vector, may be improved by the stimulation of the immune system through the presence or the expression of additional proteins, for instance vector specific proteins for instance through providing adjuvant function. However, relatively few, recombinant vector systems alone have been successful enough to be widely accepted for clinical use. Major problems other than safety have been pre-existing immunity in the case of vectors derived from infectious agents common in populations. Furthermore, subsequent immune responses against vector proteins themselves have created a further immunological barrier when more than one immunisation was required to boost responses to the recombinant vaccine antigen (s). One problem is that the immune system may mount an immune response against vector or vector encoded proteins together with an immune response against the antigen, designated the vaccination antigen, the immune response was intended to be directed toward in order to provide the host protection. The observation that the immune system may mount an immune response against a vector protein or a vector encoded protein creates a potential for competition for immune resources such as the availability of immune cells and/or cytokines, thereby lowering the desired response against vaccination proteins (see for example FIG.
1
A). Another problem is the potential for more immunogenic antigens present in vector proteins or vector encoded proteins directing the immune response away from vaccination proteins. Additionally, immune responses against the vector eventually limit vector replication in the host, thereby reducing the vectors intended purpose and effectiveness. A problem that specifically increases upon boosting of the immune response with the same or a similar vector or vector system. For instance, the use of different adenovirus serotypes comprising nucleic acid encoding similar vaccination proteins as vaccines is not optimal since the immune system will still be boosted against common antigens present in vector proteins and/or vector encoded proteins. A possible method to avoid this problem is to boost immune responses induced by the recombinant vectors with subunit protein. Several studies have shown that immune responses can be slightly improved by this method but that there is not a substantial improvement in the ability of the vaccine to protect from infection.
SUMMARY OF THE INVENTION
The present invention provides novel means and methods for obtaining a specific immune response in an individual or animal. The invention further provides means and methods for decreasing the negative effects of vector proteins and/or vector encoded proteins while leaving desired effects, such as an adjuvant effect of said proteins at least in part intact (see for a non-limiting example the scheme depicted in FIG.
1
B).
In one aspect the invention provides a product for vaccinating an animal or a human to obtain therein an immune response against at least one antigen, comprising at least two different vaccine compositions for sequential administration to said animal or said human, each containing at least said antigen or a precursor thereof, wherein at least two of said vaccine compositions differ from each other by the presence therein of a different vector.
In another aspect the invention provides a method for vaccinating an animal or human to obtain therein an immune response against at least one antigen of a virus causing a temporary, or long lasting immune impairment, comprising administering sequentially to said animal, at least two different vaccine compositions, each containing at least said antigen or a precursor thereof and wherein at least two of said vaccine compositions differ from each other by the presence therein of a different vector.
In yet another aspect the invention provides a use of an antigen, or a precursor thereof, for manufacturing a vaccine composition for vaccinating an animal or a human to obtain therein an immune response against said antigen, wherein said vaccine composition is administered sequentially with at least one other vaccine composition containing at least an immunogenic part, derivative and/or analogue of said antigen or antigen precursor, and a different vector.
DETAILED DESCRIPTION OF THE INVENTION
In one aspect the invention provides a solution to circumvent the negative effects associated with repeated exposure of vector proteins or vector encoded proteins in a vaccination procedure or a vaccine composition. To study problems associated with amplification of an immune response against vector proteins and/or vector encoded proteins a strategy was developed in which the use of different vector systems, to consecutively deliver the same or related antigen(s), was evaluated. The potential existed not only to substantially boost immune responses to the recombinant antigen, but to tailor the nature of the immune responses by priming and then delivering subsequent boosts with different vector combinations or by delivering the vaccine vectors to different immunological sites and/or antigen presenting cell populations. Indeed, the ability to induce preferred type-1 or type-2 like T-helper responses or to additionally generate specific responses at mucosal and/or systemic sites can be foreseen with such an approach.
In one aspect the invention provides means and methods for vaccinating an animal or a human to obtain therein an immune response against at least one antigen of a virus causing a temporary, or long lasting immune impairment, comprising at least two different vaccine compositions for sequential administration to said animal or said human, each containing at least said antigen or a precursor thereof, wherein at least two of said vaccine compositions differ from each other by the presence therein of a different vector. A much bett
Hoffmann & Baron , LLP
Mosher Mary E.
Stichting Biomedical Primate Research Centre
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