Immunogenic compositions comprising peptides from .beta.-2-micro

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector

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4242801, 4242781, 4242791, 4241871, 4242041, 4242081, 530324, 530325, 530326, 530327, 530328, 530329, 530330, A61K 3900, A61K 3938, A61K 3921, A61K 3912

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061139025

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BRIEF SUMMARY
The present invention relates to new types of vaccines and, in particular, to compositions intended for the treatment, prevention and diagnosis of HIV conditions.
More specifically, the present invention relates to peptides capable of producing an immune response capable of directly or indirectly neutralizing HIV viruses in mammals and in particular in man.
The importance of monoclonal antibodies directed against .beta..sub.2 -microglobulin (.beta.2m) in the inhibition of HIV-1 replication has already been described, particularly in patent EP-B-0,470,989 as well as in various publications.
In particular, it has been possible to demonstrate that these antibodies act on two mechanisms, namely directly on the virus and on the cells associated with .beta.2m.
The present invention constitutes developments of these preliminary elements and is based on the identification of peptide sequences obtained from .beta.2m or having an equivalent structure which are capable of generating antibodies completely or partially neutralizing the HIV viruses.
Given the complexity of the mechanisms used, "neutralization of the HIV virus" will be understood to mean any mechanism having the effect in vivo of destroying and/or of preventing the propagation of viruses.
In vitro, these neutralizing antibodies can be used to neutralize any body fluid intended to be reinoculated or reintroduced into man, such as the sperm of a man seropositive for HIV for the insemination of a seronegative woman.
However, more generally, the present invention is based on a new vaccinal approach which can be used, in particular, for infectious agents of the parasite or virus type with a high mutating power. Indeed, in the context of traditional vaccination, it is sought to generate neutralizing antibodies directed against components of the infectious agent, but when the latter exhibits a high mutating power, such as HIV for example, this strategy gives, at best, only limited results for a particular isolate which will be very rapidly replaced by a mutant and resistant isolate.
The new vaccinal approach is based on a different concept and is applicable to a number of infectious agents which have an intracellular phase during their cycle.
Indeed, it is known for certain agents, or it is possible to demonstrate, especially in the case of HIV, which constitutes part of the present invention, that, during the multiplication of the infectious agents from the infected cells of the host, the extracellular infectious agents carry away components of determinants of the host cell.
One of the subjects of the present invention consists in taking as target, not the infectious agent itself, but the components of the determinant which it carries away with it and to provide for a vaccination directed against these cellular determinants which will remain constant, even if the agent itself has mutated.
This type of approach has, of course, an immediate limit, the antigen being bound to the host cells, it is only possible to carry out such a vaccination with a cryptic epitope of the cellular determinant which will be exposed only when it is carried away by the extracellular infectious agent, or an epitope which is nonimmunogenic in its natural presentation by the cell and which is modified when it is presented at the surface of the virion.
In the case of HIV for example, it has been possible to demonstrate that .beta.2-microglobulin has several cryptic epitopes, which are exposed during the multiplication of the HIV virus and its passage outside the cell. There is not therefore, in the event of vaccination, on the one hand, an autoimmune reaction, and, on the other hand, the epitope being bound to the different HIV isolates which have been tested, the vaccination is effective, this being independent of the mutations of the virus itself.
This type of vaccination can be selected, in particular, for intracellular parasites and enveloped viruses such as CMV, HPV, HSV and HIV for example.
It should be clearly understood that while this type of vaccination cannot be used in all ca

REFERENCES:
patent: 5733550 (1998-03-01), Rock
Haynes, et al. : Update on the issues of the HIV vaccine development: Ann. ed. : vol. 28: pp. 39-41, 1996.
Baltimore, et al.: Defeating AIDS: what will it take? : Scientific American: pp. 81-107, Jul. 1998.
Contel et al., "Identification Of The .beta.2m Derived Epitope Responsible For Neutralization Of HIV Isolates", Cellular Pharmacology, vol. 3:68-73, (1996).

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