Using human T cell leukemia virus type III (HTLV-III) RNA to diagnose, treat and prevent infection by human aquired immunodeficiency virus; viricides
Inventors
Chang, Nancy T. • Gallo, Robert C. • Wong-Staal, Flossie
Assignees
National Institutes of Health NIH • US Department of Health and Human Services
Publication Number
US-7815916-B1
Publication Date
2010-10-19
Expiration Date
2027-10-19
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Abstract
The determination of the nucleotide sequence of HTLV-III DNA; identification, isolation and expression of HTLV-III sequences which encode immunoreactive polypeptides by recombinant DNA methods and production of viral RNA are disclosed. Such polypeptides can be employed in immunoassays to detect HTLV-III.
Core Innovation
Through cloning of HTLV-III DNA in recombinant vector-host systems capable of expressing immunoreactive HTLV-III polypeptides, the invention develops methods useful in the diagnosis, treatment, and prevention of AIDS. Methods include detecting HTLV-III and antibodies in body fluids, immunotherapy such as vaccination and passive immunization, and producing DNA and RNA probes to detect HTLV-III in body fluids. These advances enable screening of blood and body fluids to reduce disease transmission risk and provide bases for immunoassays and therapies.
Claims Coverage
The patent claims include multiple independent claims covering isolated recombinant HIV polypeptides, immunoreactive hybrid proteins, DNA constructs, methods of producing fusion proteins, and antigenic compositions. Key inventive features are identified for these claims.
Isolated recombinant HIV polypeptides immunoreactive with HIV antibodies
The invention claims isolated recombinant HIV polypeptides encoded by HIV DNA sequences identified by HIV restriction maps shown in FIG. 1 or FIG. 2, expressed by cells transformed with recombinant vectors containing the HIV DNA, wherein the polypeptides are immunoreactive with sera containing antibodies to HIV. These include polypeptides encoded by env or env-lor open reading frames and EcoRI restriction fragments, with immunoreactivity to AIDS patient sera.
Isolated recombinant immunoreactive hybrid proteins
Hybrid proteins expressed by cells transformed with recombinant vectors containing HIV gag, pol, env, or env-lor DNA linked to other polypeptides, such as indicator polypeptides including beta-galactosidase, which are immunoreactive with sera containing antibodies to HIV.
DNA constructs and nucleic acids encoding HIV polypeptides
Isolated DNAs and recombinant nucleic acids comprising HIV gag, pol, env, or env-lor sequences as shown in FIG. 1 or FIG. 2, including EcoRI restriction fragments and open reading frame DNAs, suitable for insertion into vectors to replicate and express HIV polypeptides that react with HIV antibodies.
Methods for producing HIV fusion proteins and envelope proteins
Methods involving digesting isolated HIV DNA to generate restriction fragments per FIG. 1 or FIG. 2, producing 200-500 bp fragments, inserting them into open reading frame expression vectors, transforming host cells, culturing under conditions for expression, and optionally obtaining and testing cellular protein for immunoreactivity with AIDS patient sera.
Antigenic compositions comprising recombinant HIV gag or env polypeptides
Antigenic compositions with recombinant HIV gag or env polypeptides as set forth in FIG. 3 in physiologically acceptable vehicles, wherein the antigens are at least 15 amino acids in length, optionally joined to another antigen, including specific gag p24, p15, p17, and env polypeptides encoded by defined DNA regions.
The claims cover isolated recombinant HIV polypeptides and hybrid proteins expressed from defined HIV DNA sequences, nucleic acid constructs encoding these polypeptides, methods of producing immunoreactive fusion proteins, and antigenic compositions useful for diagnosis and therapy of HIV infection and AIDS.
Stated Advantages
Provides methods for early and accurate diagnosis of AIDS by detecting HTLV-III DNA, RNA, and immunoreactive polypeptides.
Enables screening of blood and body fluids to prevent transmission of AIDS through contaminated blood products.
Facilitates production of vaccines and immunotherapies including passive immunization through antibodies against HTLV-III polypeptides.
Improves assay specificity and reduces false positives by using monoclonal antibodies against specific HTLV-III antigenic determinants.
Documented Applications
Diagnosis of AIDS by detecting HTLV-III and anti-HTLV-III antibodies in body fluids such as blood, saliva, and semen.
Screening of blood and blood components (e.g., Factor VIII for hemophilia treatment) to prevent AIDS transmission in transfusions.
Production of vaccines for immunization against HTLV-III, targeting viral envelope polypeptides to generate neutralizing antibodies.
Use of antibodies, including monoclonal antibodies, in immunoassays to detect HTLV-III antigen in body fluids.
Passive immunization therapy against HTLV-III infection using neutralizing antibodies.
Use of DNA and RNA probes specific to HTLV-III for detecting viral sequences in biological samples.
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