Abstract: The present invention comprises novel polypeptide antigens that can be used for therapeutic and prophylactic immunization against HIV-related infections. The polypeptide of the invention mimics the intermediate state of gp41 and is capable of inducing antibodies which neutralize primary isolates of HIV. The invention also comprises compositions comprising the polypeptide and methods of using it.

Abstract: Recombinant adenovirus and methods of administration to a host are provided for eliciting immune response of the host to various pathogens. In one aspect of the invention, a vaccination method is provided for enhancing immunity of the host to the pathogen through rotation of the serotypes of the recombinant adenoviruses administered to the host.

Abstract: Methods for inhibiting HIV propagation and treating HIV infection are provided which include administering to cells infected with HIV a compound capable of inhibiting viral budding from the infected host cells. The methods are especially useful in treating HIV infection and in treating and preventing AIDS.

Abstract: Attenuated recombinant viruses containing DNA encoding an immunodeficiency virus and/or CTL antigen, as well as methods and compositions employing the viruses, expression products therefrom, and antibodies generated from the viruses or expression products, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least one of: HIV1gag(+pro)(IIIB), gp120(MN)(+transmembrane), nef(BRU)CTL, pol(IIIB)CTL, ELDKWA or LDKW epitopes, preferably HIV1gag(+pro)(IIIB), gp120(MN) (+transmembrane), two (2) nef(BRU)CTL and three (3) pol(IIIB)CTL etpitopes; or two ELDKWA in gp120 V3 or another region or in gp160. The two (2) nef(BRU)CTL and three (3) pol(IIIB)CTL epitopes are preferably CTL1, CTL2, pol1, pol2 and pol3. The recombinant viruses and gene products therefrom and antibodies generated by the viruses and gene products have several preventive, therapeutic and diagnostic uses.

Abstract: End-locked five-helix protein, which is made up of three N-helices and two C-helices of HIV gp41, four inside linkers, and at least one terminal linker; the helices are connected by the inside linkers, and the terminal linker is connected to an helix and is capable of cross-linking with one of the inside linkers, is disclosed.

Abstract: Oligonucleotide sequences encoding gp120 polypeptides from breakthrough isolates of vaccine trials using MN-rgp120 and the encoded gp120 polypeptides are provided. Use of the gp120 polypeptides from one or more of the isolates in a subunit vaccine, usually together with MN-rgp120, can provide protection against HIV strains that are sufficiently different from the vaccine strain (e.g.; MN-rgp120) that the vaccine does not confer protection against those strains. Antibodies induced by the polypeptides are also provided.

Abstract: Disclosed is an immunogen in sterile form suitable for administration to a human subject, the immunogen comprising: at least a portion of the gag protein of HIV, said gag protein being from an HIV clade or having a consensus sequence for one or more HIV clades, and comprising at least parts of p17 and p24; and a synthetic polypeptide comprising a plurality of amino acid sequences, each sequence comprising a human CTL epitope of an HIV protein, and wherein a plurality of HIV proteins are represented in the synthetic polypeptide, said CTL epitopes being selected to stimulate an immune response to one or more HIV clades of interest.

Abstract: Novel antiviral combinations for the treatment or prevention of viral infections, in particular, HIV, are disclosed. This new antiviral therapy employs either DP-178 or DP-107, viral fusion inhibitors, in combination with at least one other antiviral therapeutic agent. The combinations of the invention are better than single therapies alone, and in certain cases are synergistic. The use of DP-178 or DP-107 is an ideal therapy to combine with another antiviral, given both the novel mechanism which this therapeutic blocks HIV transmission and the non-toxicity of the therapeutic.

Abstract: The present invention provides antiviral proteins, peptides and conjugates, as well as methods of obtaining these agents. The antiviral proteins, peptides and conjugates of the present invention can be used alone or in combination with other antiviral agents in compositions, such as pharmaceutical compositions, to inhibit the infectivity, replication and cytopathic effects of a virus, such as a retrovirus, in particular a human immunodeficiency virus, specifically HIV-1 or HIV-2, in the treatment or prevention of viral infection.

Abstract: A method for producing a cellular immune response in a vertebrate subject comprising administering to the vertebrate subject a vaccine composition comprising a protein particle antigen and a pharmaceutically acceptable excipient is disclosed.

Abstract: This invention relates to human immunodeficiency virus (HIV) protein fragments which have antiviral activity, and particularly relates to HIV peptides derived from the HIV transmembrane glycoprotein (gp41) which inhibit HIV-induced cell-cell fusion. This invention further relates to methods for the inhibition of enveloped viral infection, and to methods that modulate biochemical processes which involve coiled coil peptide interactions.

Abstract: The inventions discloses a pharmaceutical composition comprising an antigen, an immunostimulating substance selected from neuroactive compounds, hormones, compounds having a growth hormone activity, and mixtures thereof, and a polycationic polymer.

Abstract: The present invention provides VSV vectors comprising nucleic acid encoding a HTLV-1 viral protein, such as HTLV-1 gag and env proteins, from any strain of HTLV-1 for the production of HTLV-1 VLPs. The present invention provides VSV vectors comprising nucleic acid encoding a HPV viral protein, such as HPV L1 or L1 and L2, from any strain of HPV for the production of HPV VLPs. The present invention also provides methods of making such vectors, host cells, expression systems, and compositions comprising such VSV vectors, and viral particles comprising such VSV vectors. The present invention also provides vaccine compositions and provides methods for eliciting an immune response in an individual and methods for ameliorating symptoms of disease.

Abstract: The present invention thus provides a polypeptide capable of forming a structure corresponding to or mimicking the intermediate of gp41 as well as its use in a vaccine for treating or preventing HIV infections.

Abstract: The molecular cloning and characterization of a novel human retrovirus, designated lymphadenopathy-associated virus, or LAV, is disclosed. LAV was originally isolated from a patient with acquired immune deficiency syndrome (AIDS). A cloned LAV complementary DNA (cDNA) was used to screen a library of recombinant phages constructed from the genomic DNA of LAV-infected T lymphocytes. The nucleotide sequence of an insert obtained from the recombinant phage clone &lgr;J19 was ascertained through M13 shotgun cloning and the dideoxy chain termination sequencing method. The env coding region was identified and peptides obtained therefrom. These peptides correspond to amino acids 239-294, 273-317, 300-327, 334-381, 397-424, and 466-500 of the LAV env. These peptides provide suitable diagnostic reagents for the detection LAV-specific antibodies and for the generation of LAV-specific immunological reagents.

Abstract: Genetic vaccines and methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one embodiment, a recombinant benign virus is provided as the genetic vaccine. The recombinant virus comprises: an antigen sequence heterologous to the recombinant virus that encodes a viral antigen from a pathogenic virus, expression of the viral antigen eliciting an immune response directed against the viral antigen and cells expressing the viral antigen in a host upon infection of the host by the recombinant virus; and an immuno-stimulator sequence heterologous to the recombinant virus that encodes an immuno-stimulator whose expression in the host enhances the immunogenicity of the viral antigen. The recombinant virus is replication-incompetent and does not causes a malignancy naturally associated with the pathogenic virus in the host.

Abstract: Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis.

Abstract: A method for the rational design and preparation of vaccines based on HIV envelope polypeptides is described. In one embodiment, the method for making an HIV gp120 subunit vaccine for a geographic region comprises determining neutralizing epitopes in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region and selecting an HIV strain having gp120 a neutralizing epitope in the V2 or C4 domain which is common among isolates in the geographic region. In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 are determined. At least two HIV isolates having different neutralizing epitopes in the V2, V3, or C4 domain are selected and used to make the vaccine. The invention also provides a multivalent HIV gp120 subunit vaccine.

Abstract: The invention relates to the sequence of the capsid gene and a corresponding cDNA sequence, of a dominant FCV strain called FCV 431. It also relates to the sequence of the capsid gene as well as the cDNA sequence of a complementary strain called G1. The cDNA sequences may be incorporated into expression vectors for the preparation of immunogenic preparations and of recombinant or subunit vaccines allowing vaccination against feline calicivirosis.

Abstract: A live attenuated human immunodeficiency virus type 1 (HIV-1) whose replication is not constitutive but is instead conditionally regulated (such that rounds of reverse transcription with accompanying potential for error are strictly limited) might yield a paradigm that minimizes evolution to virulence and facilitate vaccine development. We have broached the concept of conditional control of HIV-1 through gain-of-function. Here, we describe the design of constitutively inactive HIV-1 genomes (HIV-DoxT and HIV-DoxSp) which can be conditionally resuscitated to an active state by tetracycline or related analogues. The HIV-DoxT construct comprises an inactivating mutation engineered into TAR, thereby rendering the virus non-responsive to Tat, a 302-bp DNA fragment (TetopT) which contains the tet-operator ligated into a position upstream of the HIV TATAA box, in both the 5′ and 3′ LTRs, and a reverse tetracycline-controlled activator (RTTA) coding sequence in place of the nef coding region.

Abstract: The present invention provides a method of synthesizing genes encoding unique HIV-1 and HIV-2 envelope proteins and their fragments, thereby allowing overexpression of these proteins in E. coli. The HIV envelope proteins and their fragments have been expressed at high levels as individual proteins or in fusion with other proteins. The HIV envelope proteins thus expressed in E. coli can be effectively used for the detection of exposure to HIV as well as the discrimination of HIV-1 and HIV-2.

Abstract: The present invention is directed to a bacterial delivery system for delivering alphavirus replicon DNA into an animal or animal cells with the replicon encoding one or more heterologous genes to be expressed in the animal or the animal cells. The bacteria are invasive bacteria or attenuated invasive bacteria engineered to contain a DNA vector that encodes the alphavirus replicon in a eukaryotic expression cassette. The heterologous gene can encode an antigen, a therapeutic agent, an immunoregulatory agent, an anti-sense RNA, a catalytic RNA, a protein, a peptide, an antibody or an antigen-binding fragment of an antibody. In a preferred embodiment, the heterologous gene encodes one or more antigens useful as a vaccine for HIV. In addition to the bacterial delivery system, the invention provides methods of introducing and expressing the heterologous gene(s) in animal or animal cells and methods of stimulating or inducing an immune response.

Abstract: The present invention relates generally to programmed cell death and specifically to methods, compositions, and kits for preserving or enhancing antigenicity of markers associated with disease by utilizing inhibitors of apoptosis including interleukin-1&bgr;-converting enzyme (ICE)/CED-3 family inhibitors.

Abstract: The present invention describes recombinant p24/p17 hybrid protein derived from the human immunodeficiency virus, their corresponding encoding recombinant DNA molecule and the process of production of the recombinant protein produced through genetic engineering techniques, to be used in diagnosis, vaccination or in research.

Abstract: RNA polymerase I transcription in vivo in transiently DNA-transfected cells has been used for expression of influenza vRNA molecules coding for chloramphenicol acetyltransferase (CAT) in anti-sense orientation. Influenza virus superinfection served to provide viral RNA polymerase and other proteins for transcriptional conversion of minus-strand vRNA into plus-strand viral mRNA molecules expressing CAT activity. This system has been used for an analysis via nucleotide exchanges as well as deletions and insertions of both terminal segments of the vRNA sequence which cooperatively constitute the vRNA promoter structure. Several mutants with greatly enhanced expression rates over wild-type levels have been constructed, which also can be packaged and serially passaged into progeny virus. The data obtained for the mutations in various promoter elements support a model of consecutive, double strand vRNA promoter structures in binding of viral polymerase and initiation of RNA synthesis.

Abstract: A novel method of immunization, which can be used either prophylactically or therapeutically, is described. The method comprises coating of antigen presenting cells with a peptide and administering the peptide-coated cells to a mammalian subject to provoke an immune response. Useful peptides include peptides derived from viral or bacterial antigens or mutant oncogene or tumor suppressor gene products. Immunogens, constituted by the peptide-coated cells, are also described.

Abstract: The present invention relates to methods for treating immunodeficiency virus infection in an infected animal comprising administering an effective amount of a lytic peptide.

Abstract: This invention is directed toward the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of AIDS, both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. However, preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1 positive sera. Overlapping molecular clones were obtained and the complete nucleotide sequence of the gag and env genes was ascertained.

Abstract: A vaccine for treating and/or preventing infectious diseases where the infectious agent has at least one intracellular phase in the host during its multiplication cycle, is disclosed. The vaccine comprises at least one cryptic epitope of a cellular element that is carried along by an intracellular infectious agent as it leaves the cell, and revealed by said infectious agent. A composition for treating and/or preventing HIV infections, antibodies to a peptide of interest, and a diagnostic method, are also disclosed.

Abstract: The present invention relates to a DNA or RNA construct capable of expression of IL-2 in a warm-blooded animal or biological preparation, the recombinant DNA or RNA construct comprising a) a Vpr activated promoter; b) a transcribable DNA segment coding for IL-2 and; c) a secretory DNA encoding for a signal peptide functional in mammary cells and operably linked between the promoter and the DNA segment to facilitate secretion of the IL-2. The present invention also relates to a method for increasing the immune response of a warm-blooded animal or biological preparation. There is also described methods for inhibiting or stimulating expression of IL-8 of a warm-blooded animal or a biological preparation.

Abstract: The invention provides peptides which are expressed by the env gene of a non-M, non-O HIV-1 virus, in particular a strain designated YBF30. The invention also provides fragments of the peptides that including the V3 loop region and their corresponding nucleotide sequences. The invention further provides kits including diagnostic reagents containing these molecules or immunogenic compositions containing these peptides, as well as methods for screening and typing non-M, non-O HIV-1 viruses and HIV-1 viruses expressing these peptide and/or nucleotide sequences.

Abstract: Human immunodeficiency virus (HIV) comprising reverse transcriptase inactivated by photoinactivation. The inactivated virus may be more safely handled, stored, and analyzed, used in diagnostic procedures and kits, and may be used as an immunogen to evoke an immune response. The immune response may protect an individual from challenges with live virus. Alternatively, the inactivated HIV particles may be used to augment the immune response to HIV in an infected individual.

Abstract: The present invention relates to a novel antigenic/immunogenic peptide derived from the CCR5 chemokine receptor, useful in the treatment of HIV infection.

Abstract: Disclosed are gene therapy vectors based on chimeric murine leukemia virus-feline immunodeficiency virus gene therapy vectors which are suitable for a wide variety of gene therapy applications. Also disclosed are related packaging cell lines, methods for production, and methods of use.

Abstract: The invention disclose a pharmaceutical composition comprising an antigen, an immunogenic CpG-ODN and a polycationic polymer.

Abstract: A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y7-Leu-X8-Pro-Trp-Z12-R2 (SEQ ID NO: 8). In this composition, at least one of the two variants contains Arg at Y7 and Lys at Z12, and in at least a second of the two variants Y7 is Asn and Z12 is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Abstract: Recombinant human immunodeficiency virus antigens capable of immunologically identifying the presence of early anti-HIV antibodies are stably expressed in a number of cell lines. These antigens have several clinically important applications as non-hazardous tools in the detection of human immunodeficiency virus exposure/infection, and in screening methods for HIV infection in idiopathic chronic lymphopenia (ICL). These techniques are improved over existing immunologically based and PCR based detection methods, as they provide for the detection of infection/exposure in samples determined to be negative by conventional forms of these types of assays that do not detect anti-HIV gp160 antibodies that react to conformational epitopes of HIV. The invention finds particular application in the detection of human immunodeficiency virus exposure/infection in infants.

Abstract: The invention provides HIV vaccine candidates that have “evolved” due to gene shuffling in vitro for inclusion of “cross-clade” characteristics. The invention also provides a method for identifying HIV vaccine candidates that could be presented in the context of more than one HLA, due to the creation of promiscuous epitopes by gene shuffling.

Abstract: Enveloped virus vectors are described which comprise a cellular virus receptor protein and which are capable of fusing with a cell which comprises a viral envelope protein to which the cellular virus receptor protein is cognate. Enveloped virus vectors comprising a plurality of cellular virus receptor proteins are also described. Methods for making the enveloped virus vectors are described, as are methods of using the enveloped virus vectors. The invention further relates to a lipoparticle comprising a membrane spanning protein, and the lipoparticle can be attached to a sensor surface. The invention relates to methods of producing and using the lipoparticle to, inter alia, assess protein binding interactions.

Abstract: A method of preventing a respiratory infection by administering DNA which encodes IFN is provided. Also provided is a therapy for the prevention of a respiratory infection containing DNA which encodes IFN.

Abstract: A variant of a LAV virus, designated LAVMAL and capable of causing AIDS. The cDNA and antigens of the LAVMAL virus can be used for the diagnosis of AIDS and pre-AIDS.

Abstract: A novel compound, which is effective for treatment of AIDS and has inhibitory activity on human immunodeficiency viruses (HIV), was examined. The K97-0003 peptide, which has anti-HIV activity caused by inhibition of syncytium formation by fusion of envelope glycoprotein of HIV and the host cells expressing the receptor to said virus, was provided by the present invention. Furthermore, the base sequence of the gene coding for said polypeptide, and the method for preparing said polypeptide using strain K97-0003 were provided.

Abstract: A variant of a LAV virus, designated LAVMAL and capable of causing AIDS. The cDNA and antigens of the LAVMAL virus can be used for the diagnosis of AIDS and pre-AIDS.

Abstract: The present invention provides adeno-associated virus (AAV) materials and methods which are useful for DNA delivery to cells. More particularly, the invention provides recombinant AAV (rAAV) genomes, methods for packaging rAAV genomes, stable host cell lines producing rAAV and methods for delivering genes of interest to cells utilizing the rAAV. Particularly disclosed are rAAV useful in generating immunity to human immunodeficiency virus-1 and in therapeutic gene delivery for treatment of neurological disorders.

Abstract: A novel vaccine composition combines a protein or peptide antigen, optionally added hydrophobic material and an immunopotentiating membranous carrier which together preserve the antigenic integrity of the protein or peptide epitopes while at the same time enhancing their immunogenicity. Administration of this composition to a subject provokes a protective immune response comprising secretory neutralizing antibodies present in various mucosal sites in the body. This vaccine and the process for using it is intended for use against pathogenic organisms, in particular those causing sexually transmitted diseases or mucosally transmitted diseases. Such organisms include bacteria and enveloped viruses, particularly HIV-1.

Abstract: The invention relates to chimeric molecules comprising a virus coat sequence and a receptor sequence that can inter-act with each other to form a complex that is capable of binding a co-receptor. Such chimeric molecules therefore exhibit functional properties characteristic of a receptor-coat protein complex and are useful as agents that inhibit virus infection of cells due to occupancy of a co-receptor present on the cell. In particular aspects, the chimeric polypeptide includes an immunodeficiency virus envelope polypeptide, such as that of HIV, SIV, FIV, FeLV, FPV and herpes virus. Receptor sequences suitable for use in a chimeric polypeptide include, for example, CD4 D1D2 and CD4M9 sequences.

Abstract: A novel immunodeficiency virus is disclosed which has the designation MVP-5180/91 and which has been deposited with the European Collection of Animal Cell Cultures (ECACC) under No. V 920 52 318. The characteristics antigens which can be obtained from it and which can be employed for detecting antibodies against retroviruses which are associated with immunodeficiency diseases are also disclosed, as are the DNA and amino acid sequences of the virus.

Abstract: Compositions and methods are provided which may be used to advantage for the treatment of HIV infection.

Abstract: The present invention relates to a Vpr protein, a Vpx protein or fragments thereof which permit the development of chimeric molecules that can be specifically targeted into the mature HIV-1 and HIV-2 virions to affect their structural organization and/or functional integrity, thereby resulting in gene therapy for HIV-1 and HIV-2 infections. The present invention also relates to Vpr/Vpx protein Fragments, p6 protein, p6 protein fragment, or functional derivatives thereof which interfere with the native Vpr/Vpx incorporation into HIV-1 and HIV-2 virions. The present invention also relates to treatment of HIV-1 and HIV-2 infections based on the proteins of the present invention.

Abstract: An active peptide consisting essentially of 7 to about 30 residence and having a sequence that corresponds to a conserved domain of an HIV protein is disclosed, as is a multimer containing that peptide, an aqueous composition containing the multimer and methods of using and making the same. The aqueous composition containing an immunologically effective amount of an active peptide multimer, when introduced into an immunocompetent host animal in an immunologically effective amount, is capable of inducing cellular immunity against the native HIV protein to which the active peptide of the multimer corresponds in sequence, but is not capable of inducing production of antibodies that immunoreact with that native HIV protein.