Abstract: The present invention relates to isolated immunogenic polypeptides and their use. In one aspect, the isolated immunogenic polypeptide includes a scaffold polypeptide having a hairpin loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond. The scaffold polypeptide directs self-assembly with two other of the scaffold polypeptides to form a trimeric structure, which constrains the one or more epitopes to a conformation that is (i) substantially similar to one or more native pathogen epitopes in trimeric conformation and (ii) capable of binding an antibody reactive to the one or more native pathogen epitopes in trimeric conformation. Another aspect relates to an isolated immunogenic polypeptide that includes a scaffold polypeptide having a native loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond.

Abstract: The present invention relates to isolated immunogenic polypeptides and their use. In one aspect, the isolated immunogenic polypeptide includes a scaffold polypeptide having a hairpin loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond. The scaffold polypeptide directs self-assembly with two other of the scaffold polypeptides to form a trimeric structure, which constrains the one or more epitopes to a conformation that is (i) substantially similar to one or more native pathogen epitopes in trimeric conformation and (ii) capable of binding an antibody reactive to the one or more native pathogen epitopes in trimeric conformation. Another aspect relates to an isolated immunogenic polypeptide that includes a scaffold polypeptide having a native loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond.

Abstract: The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.

Abstract: The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.

Abstract: The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.

Abstract: A number of peptide epitopes and fragments from three Mycobacterium tuberculosis (Mtb) cell wall proteins have been identified as early antigens that induce antibodies early during Mtb infection in humans. The proteins are Proline-Threonine Repetitive Protein (PTRP), PE-PGRS51, and LipC. These peptides, alone or in mixtures, or as parts of fusion polypeptides or peptide multimers, are useful as antigens for serological detection of early in infection by detecting the presence of early antibodies against these proteins, thereby permitting earlier diagnosis of Mtb infection than was heretofore possible by conventional means. The above peptides and other peptide-based compositions are also used as immunogens for inclusion in TB vaccines. Also provided are methods for early diagnosis of Mtb infection and for immunizing a subject to prevent or treat Mtb infections and tuberculosis.

Abstract: Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely related E. coli enterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.

Abstract: The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.

Abstract: The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.

Abstract: A number of peptide epitopes and fragments from three Mycobacterium tuberculosis (Mtb) cell wall proteins have been identified as early antigens that induce antibodies early during Mtb infection in humans. The proteins are Proline-Threonine Repetitive Protein (PTRP), PE-PGRS51, and LipC. These peptides, alone or in mixtures, or as parts of fusion polypeptides or peptide multimers, are useful as antigens for serological detection of early in infection by detecting the presence of early antibodies against these proteins, thereby permitting earlier diagnosis of Mtb infection than was heretofore possible by conventional means. The above peptides and other peptide-based compositions are also used as immunogens for inclusion in TB vaccines. Also provided are methods for early diagnosis of Mtb infection and for immunizing a subject to prevent or treat Mtb infections and tuberculosis.

Abstract: A novel immunogenic HIV-1 Env, particularly gp120, DNA construct is disclosed in which either the V1/V2 loop and the V4 loop, or all three variable loops, including V3, are replaced with a V3 sequence each of which is from a different viral isolate. Preferably, each replacement V3 loop is a consensus sequence of V3 of a different clade. Such constructs are useful as immunogens as each presents three independent V3 epitopes, so that the immunized subject generates a more broadly reactive neutralizing antibody response than with conventional gp120 or V3 DNA or polypeptide immunogens. Also disclosed are methods of using the DNA construct to immunize a mammal, preferably a human, particularly in a priming regiment in which the DNA immunogen is followed by administration of a V3 fusion protein boosting immunogen.

Abstract: The present invention provides constrained peptides and other organic molecules, that mimic the three dimensional characteristics of the HIV-1 V3 loop peptide when bound by a highly potent human neutralizing monoclonal antibody specific for a V3 conformational epitope, which structure is determined by NMR. Methods for screening for, and designing such molecules are disclosed. These molecules are useful as immunogens for inducing broadly-neutralizing antibodies against HIV-1 as well as antagonists for inhibiting the binding of HIV-1 to the relevant co-receptors, and may therefore be used in method of preventing or treating HIV-1 infection and disease.

Abstract: A number of protein and glycoprotein antigens secreted by Mycobacterium tuberculosis (Mtb) have been identified as “early” Mtb antigens on the basis early antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. Epitope-bearing peptide fragments of these early Mtb antigens, in particular of an 88 kDa secreted protein, GlcB (SEQ ID NO:106) and of Mtb antigen MPT51 (SEQ ID NO:107) have been identified. These peptides, variants thereof, peptide multimers thereof that include two or more repeats of one or more of the peptides, and fusion polypeptides that include early Mtb antigenic proteins, peptides or both, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mtb antibodies. The antigenic proteins and peptides are also used in vaccine compositions.

Abstract: A number of protein and glycoprotein antigens secreted by, or expressed on the surface of, Mycobacterium tuberculosis (Mtb) have been identified as “early” Mtb antigens on the basis of antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. PirG protein encoded by the Mtb gene Rv3810, PE-PGRS protein encoded by the Mtb gene Rv3367, PTRP protein encoded by the Mtb gene Rv0538) and MtrA protein encoded by the Mtb gene Rv3246c, or epitopes of these proteins, are useful in immunoassay methods or T cell assays for early, rapid detection of TB in a subject. Preferred immunoassays detect antibodies in the urine. Also provided are antigenic compositions, kits and methods useful for detecting these early Mtb antigens and early Mtb antibodies specific for them. Vaccine compositions comprising the foregoing antigens or epitopes are also disclosed.

Abstract: Newly discovered structural characteristic of the gp120 V3 loop have resulted in a “rule” or algorithm, that is used in a method for determining whether a subject is infected with HIV-1 virus that expresses selectivity for CXCR4 or CCR5 chemokine receptors. A positively charged surface patch defined by V3 loop residues 11 and 24 or 25 at the base of the ?-strands in the V3 loop and the homologous ?2-?3 chemokine hairpin is responsible for CXCR4 receptor selection. Thus a method for detecting the presence of HIV-1 virus that is selective for X4-co-receptors in a subject infected with HIV-1 or suspected of being infected, from the amino acid sequence of at least a part of the HIV-1 gp120 V3 region peptide that includes residues 11, 24 and 25, or from the nucleotide sequence of a nucleic acid encoding said V3 region peptide, is disclosed.

Abstract: A number of protein and glycoprotein antigens secreted by Mycobacterium tuberculosis (Mtb) have been identified as “early” Mtb antigens on the basis early antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. Epitope-bearing peptide fragments of these early Mtb antigens, in particular of an 88 kDa secreted protein, GlcB (SEQ ID NO:106) and of Mtb antigen MPT51 (SEQ ID NO:107) have been identified. These peptides, variants thereof, peptide multimers thereof that include two or more repeats of one or more of the peptides, and fusion polypeptides that include early Mtb antigenic proteins, peptides or both, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mtb antibodies. The antigenic proteins and peptides are also used in vaccine compositions.

Abstract: Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely related E. coli enterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.

Abstract: Compositions, kits and methods for boosting, or for priming and boosting, high titer broadly neutralizing cross-clade antibody responses focused on single HIV-1 neutralizing epitopes are disclosed. gp120 DNA plasmids comprising HIV env genes are used to prime the antibody response. Primed subjects are immunized with recombinant fusion proteins that comprise a “carrier” protein fusion partner, preferably a truncated form of the MuLV gp70 Env protein, and a desired HIV neutralizing epitopes. Preferred epitopes are epitopes of V3 from one or more HIV clades. Immune sera from such immunized subjects neutralized primary isolates from virus strains heterologous to those from which the immunogens were constructed. Neutralizing activity was primarily due to V3-specific antibodies and cross-clade neutralizing Abs were present. This approach results in more potent and broader neutralizing antibody levels, a result of “immunofocusing” the humoral immune response on neutralizing epitopes such as V3.

Abstract: The present invention provides constrained peptides and other organic molecules, that mimic the three dimensional characteristics of the HIV-1 V3 loop peptide when bound by a highly potent human neutralizing monoclonal antibody specific for a V3 conformational epitope, which structure is determined by NMR. Methods for screening for, and designing such molecules are disclosed. These molecules are useful as immunogens for inducing broadly-neutralizing antibodies against HIV-1 as well as antagonists for inhibiting the binding of HIV-1 to the relevant co-receptors, and may therefore be used in method of preventing or treating HIV-1 infection and disease.

Abstract: A novel immunogenic HIV-1 Env, particularly gp120, DNA construct is disclosed in which either the V1/V2 loop and the V4 loop, or all three variable loops, including V3, are replaced with a V3 sequence each of which is from a different viral isolate. Preferably, each replacement V3 loop is a consensus sequence of V3 of a different clade. Such constructs are useful as immunogens as each presents three independent V3 epitopes, so that the immunized subject generates a more broadly reactive neutralizing antibody response than with conventional gp120 or V3 DNA or polypeptide immunogens. Also disclosed are methods of using the DNA construct to immunize a mammal, preferably a human, particularly in a priming regiment in which the DNA immunogen is followed by administration of a V3 fusion protein boosting immunogen.