Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
2001-03-09
2003-11-04
Housel, James (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C424S093200, C424S205100, C424S206100, C424S207100, C424S232100, C435S236000, C435S320100
Reexamination Certificate
active
06641816
ABSTRACT:
The present invention relates to a method for enhancing the specific immune response against an immunogenic compound, which comprises administering the immunogenic compound together with a poxvirus, recombinant or not.
Smallpox, a human infectious disease due to a vaccinia virus, was declared eradicated from the globe in 1980. This unique success was made possible by the availability of an effective virus-attenuated vaccine. Concurrent with the smallpox eradication and the cessation of vaccination, a new use for the vaccinia virus was proposed (Panicali & Paoletti, PNAS (1982) 79:4927). Utilizing molecular cloning techniques, it became possible to express genes from foreign pathogens in vaccinia virus providing new approaches to vaccination.
Since then, the original technology has been applied to the whole poxvirus family, including not only the vaccinia virus but also avipoxviruses such as fowlpox and canarypox. In order to address the issue of safety, a strategy was developed to genetically engineer a highly attenuated vaccinia virus such as the Copenhagen strain that would still retain the ability to induce vigorous immunological response against extrinsic antigens. A number of poxvirus constructions have been tested in clinical trials. As a matter of example, they include recombinant vaccinia and canarypoxviruses expressing Human Immunodeficiency Virus (HIV) or
Plasmodium falciparum
antigens. Further, it has already been proposed to combine, in an immunization protocol, a prime-administration using a recombinant poxvirus vector and booster-administrations of the purified polypeptide as encoded by the recombinant vector (See e.g., Excler & Plotkin, AIDS (1997) 11 (suppl. A): S127). Such immunization protocols are commonly referred as prime-boost protocols and are very advantageous in a number of cases, in particular for AIDS treatment or prevention.
Prime-boost protocols are however unpractical both for physicians, manufacturers and sellers, in that they require two different pharmaceutical products that have to be each identified and licensed for their specific use (priming or boost).
It has now been found that poxvirus particles may be useful as enhancer of specific immunity. Indeed, it has been observed that the immune response against a vaccinal antigen, such as an HIV or an influenza virus protein, is enhanced, when it is mixed with a poxvirus, recombinant or not. Additionally, It has also been found that an immunization protocol exclusively using a composition comprising a polypeptide and a poxvirus encoding this polypeptide, may be just as good as a prime-boost protocol. It has also surprisingly been found that the observed immunization effect is not a mere additional effect, but results from a synergism effect between the two components.
Therefore, the invention provides for:
(i) The use of a poxvirus for the manufacture of a pharmaceutical composition comprising an immunogenic compound for inducing an immune response in a vertebrate, wherein the poxvirus is able to enhance a specific immune response to the immunogenic compound.
(ii) The use of a mixture comprising (a) an immunogenic compound which comprises at least one antigenic determinant characteristic of a pathogenic microorganism or is cross-reactive with a tumor-associated antigen (TAA) and (b) a poxvirus; in the manufacture of a medicament to be administered to a vertebrate for treating or preventing an infection induced by the pathogenic microorganism or a tumoral disorder characterized by the malignant expression of the TAA; whereby said poxvirus enhances the specific immune response of the vertebrate against said immunogenic compound.
(iii) A pharmaceutical composition comprising (a) an immunogenic compound and (b) a poxvirus encoding an heterologous polypeptide which is selected from the group consisting of adhesion molecules, co-immunostimulatory molecules, apoptotic factors, cytokines, chemokines and growth hormones.
(iv) A pharmaceutical composition comprising (a) an immunogenic compound which is a first polypeptide and (b) a poxvirus encoding an heterologous polypeptide,which has an amino acid sequence identical to the amino acid sequence of the first polypeptide.
(v) A pharmaceutical composition comprising (a) an immunogenic compound which is a DNA plasmid encoding a first polypeptide and (b) a poxvirus encoding a second heterologous polypeptide, which has an amino acid sequence identical to the amino acid sequence of the first polypeptide.
(vi) A method for enhancing the specific immune response of a vertebrate to an immunogenic compound, which comprises administering to the vertebrate the immunogenic compound together with a poxvirus, whereby the poxvirus enhances the specific immune response to the immunogenic compound.
(vii) A method for treating or preventing in a vertebrate, a disorder either induced by a pathogenic microorganism or characterized by the malignant expression of a T.A.A, which comprises administering to the vertebrate, (a) an immunogenic compound which comprises at least one antigen determinant characteristic of the pathogenic microorganism or a tumor-associated antigen together with (b) a poxvirus; whereby a specific immune response to the immunogenic compound is induced in the vertebrate and whereby the poxvirus enhances the specific immune response.
(viii) A method for enhancing the specific “in vitro” immunostimulation of cells from an immune system against a specific immunogenic compound, which comprises (a) recovering cells from a vertebrate, (b) “in vitro” incubating the cells with the immunogenic compound together with a poxvirus, whereby the cells are immunostimulated against the immunogenic compound and whereby the poxvirus enhances the immunostimulation and (c) administering the immunostimulated cells obtained from step (b) to a vertebrate.
In a general manner, there exist two types of immunity: the innate immunity and the acquired immunity. The former which is phylogenetically older brings into play soluble molecules, i.a. complement factors and cells, such as NK cells or macrophages, which are innately programmed to detect noxious substances produced by pathogenic microorganisms and to provide for rapid but often incomplete antimicrobial host defense. The innate immune system intervenes as the first line of defense when an infectious agent attacks an individual. On the other hand, the innate immune system can not be educated by the antigens expressed by the pathogenic microorganisms or tumor cells during the life of an individual and in this respect; the innate immunity is confounded with the natural immunity. By contrast, the acquired immune system brings into play antigen-specific B and T lymphocyte clones the affinity of which increases by the time consecutively to repeated contacts with the specific antigen. Moreover, some of them behave as memory lymphocytes, since they have a long lasting life and are able to proliferate and expand rapidly consecutively to a further contact with a specific antigen, so that these memory lymphocytes contribute to the long term protection of an individual to infectious microorganisms. An essential goal of vaccination is to provide for these memory lymphocytes.
Accordingly, by “specific immune response” is meant a specific humoral and/or a specific cellular immune response against the immunogenic compound of the pharmaceutical composition. In the present invention, the specific humoral immune response includes both systemic and mucosal antibody responses since, to feature the humoral response, one may refer to all types of specific antibodies, i.e. IgM, all subclasses of IgG and IgA, that may be elicited by the pharmaceutical composition. The specific lymphoproliferative response and the specific cytotoxic T lymphocyte (CTL) response preferentially are the main parameters of the specific cellular immune response.
For use in the present invention, the immunogenic compound may be a chemical or a biological material that is able to induce a humoral or cellular immune response in a vertebrate. A biological material may be e.g., an
Chevalier Michel
Meignier Bernard
Moste Catherine
Sambhara Suryaprakash
Aventis Pasteur S.A.
Housel James
Li Bao Qun
McDonnell & Boehnen Hulbert & Berghoff
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