Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1995-04-20
1999-10-12
Eisenschenk, Frank C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
4241841, 4242081, 530395, 530350, 435 5, 435 71, 435 72, A61K 3921, A61K 3938, C07K 1400, C07K 100
Patent
active
059651350
DESCRIPTION:
BRIEF SUMMARY
The invention relates to new HIV-1 virus isolates of a subtype, vaccines against HIV-1 virus infections of this subtype, methods of producing same, and the use of the virus isolates for the production of vaccines and for differential diagnostics.
Hitherto, efforts to develop agents for the prophylaxis and therapy of HIV infections have focused on the inhibition of the reverse transcriptase or some other enzyme of the HIV-1 virus such as, for example, protease. Thereby a specific inhibition of viral replication in contrast to cellular replication is intended to be accomplished. Nevertheless, the antiviral agents of prior art suffer from the drawback that they are accompanied by a relatively high toxicity towards the cells, i.e. they do not only affect the virus.
Those groups of substances which have been identified as being active against HIV viruses include, inter alia, various nucleoside analogues (azidothymidine, di-deoxyinosine and di-deoxycytidine). However, a massive formation of resistence of the virus has been detected after some relatively short periods of therapy with these substances {Zimmermann et al., Abstract No. 3656, IV International Conference on AIDS, Stockholm, 1988, Rubsamen-Waigmann et al., Infection 19, Suppl. 2, 77-82, 1991}. Furthermore, all of the substances mentioned produce considerable side-effects, at least when applied in higher doses.
Another inhibitor of reverse transcriptase is the substance Suramin. However, this substance, due to its toxicity towards the mammal organism, is also not suitable for prophylaxis or therapy of HIV-virus infections {H. Mitsuya et al. "Suramin Protection of T-Cells in vitro against Infectivity and Cytopathic Effect of HTLV-III", Science 226 (1984), pages 172-174}.
Further development has led to reverse transcriptase inhibitors which are less toxic towards the mammal organism. These include substances such as dextran sulfate and pentosan polysulfate, which have proven to display a HIV-1-inhibiting effect in vivo, as has been described in DE 36 01 136 and in EP 0 293 826.
In addition to a chemotherapeutic treatment of HIV infections there is basically the possibility of a gene therapy or immunotherapy. Gene therapy comprises the incorporation of parts of viral nucleic acids in human cells, especially in the target cells of the HIV virus, for example the CD4-positive cells of the immune system. Then, the viral messenger RNA (m-RNA) can be neutralized by the formation of an "antisense" RNA, i.e. an RNA complementary to m-RNA, and hence the virus proliferation can be terminated. In some other form, oligonucleotides or structures chemical related thereto that are complementary to m-RNA can be employed. In immunotherapy, antigens are administered after the infection which are expected to support the immune response to HIV.
Meanwhile, the World Health Organization (WHO) estimates a number of at least 13 million of HIV-infected people worldwide; no country has been left free from infections with HIV-1 or HIV-2 or both viruses at the same time. It is urgently necessary to develop a vaccine for protection from HIV infections in order to prevent the epidemic from farther spreading. Here, and also in immunotherapy, the main problem is the high variability of the HIV viruses: a prophylactic inoculation should and must include all of the possible virus variants. Epidemiologic investigations in combination with the genetic characterization of the viruses produced the result that several subtypes do already exist in both virus families {Myers et al., Human Retroviruses and AIDS, Los Alamos, 1991; Dietrich et al., Nature 342, 948-950, 1989}, which subtypes are significantly distinguished from one another with respect to their hereditary information to a degree such that one single vaccine will not be capable to be active against all variants. Moreover, these subtypes are also subject to different geographic distributions.
The present invention provides three new HIV 1 virus isolates HIV-1.sub.D757, HIV-1.sub.D747, HIV-1.sub.D760, which, surprisingly, form a further
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Dietrich Ursula
Grez Manuel
Rubsamen-Waigmann Helga
Von Briesen Hagen
Chemotherapeutisches Forschungsinstitut
Eisenschenk Frank C.
Nelson Brett
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