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: Protective high molecular weight (HMW) proteins are produced recombinantly by expression from E. coli by using a promoter effective in E. coli and a nucleic acid molecule which contains a modified operon of a non-typeable strain of Haemophilus. The modified operon contains the portion only of the A region which encodes the mature HMW protein and the complete B and C regions of the operon. Enhanced levels of expression of the HMW proteins can be achieved by including the E. coli cer gene, a further copy of the portion of the A region of the operon encoding the mature protein or both in the expression vector. Nucleotide and deduced amino acid sequences of the hmw1 and hmw2 genes and HMW1 and HMW2 proteins, respectively of several non-typeable Haemophilus influenzae strain have been identified.

Abstract: The fusion (F) protein, attachment (G) protein and matrix (M) protein of respiratory syncytial virus (RSV) are isolated and purified from respiratory syncytial virus by mild detergent extraction of the proteins from concentrated virus, loading the protein onto a hydroxyapatite or other ion-exchange matrix column and eluting the protein using mild salt treatment. The F, G and M proteins, formulated as immunogenic compositions, are safe and highly immunogenic and protect relevant animal models against decreased caused by respiratory syncytial virus infection.

Abstract: Adjuvant compositions for modulating an immune response to an antigen administered to a host comprise a mineral salt adjuvant and at least one other adjuvant. The compositions provide an adjuvanting effect on an antigen which is greater than the adjuvanting effect attainable by one of the adjuvants alone. An antigen is covalently bonded to a glycolipid analog to provide a discrete molecule which exhibits an enhanced adjuvanting effect on the antigen which is greater than the adjuvanting effect attainable in the absence of such covalent bonding.

Abstract: A virus neutralizing level of antibodies to a primary HIV isolate is generated in a host by a prime-boost administration of antigents. The primary antigen is a DNA molecule encoding an envelop glycoprotein of a primary isolate of HIV-1 while the boosting antigen is either a non-infectious, non-replicating HIV-like particle having the envelope glycoprotein of a primary isolate of HIV-1 or an attenuated viral vector expressing an envelope glycoprotein of a primary isolate of HIV-1.

Abstract: Vectors containing a nucleotide sequence coding for an F protein of respiratory syncytial virus (RSV) and a promoter for such sequence, preferably a cytomegalovirus promoter, are described. Such vectors also may contain a further nucleotide sequence located adjacent to the RSV F protein encoding sequence to enhance the immunoprotective ability of the RSV F protein when expressed in vivo. Such vectors may be used to immunize a host, including a human host, by administration thereto. Such vectors also may be used to produce antibodies for detection of RSV infection in a sample.

Abstract: Antibody molecules specific for surface structures of antigen presenting cells that have been modified to include an antigen moiety at a specific site therein to produce novel conjugate antibody molecules are disclosed. These conjugate molecules are produced by genetic modification of genes encoding light and heavy chains of the surface structure specific antibody, and expression in mammalian cells to produce the conjugate antibody. The conjugate antibody retained specificity for antigen presenting cells and contained the antigen moiety. The conjugate antibody molecules deliver the antigen to antigen presenting cells to produce an enhanced immune response to a host immunized therewith. The conjugate antibody molecules and nucleic acid molecules encoding them are useful as antigens and as immunogene in diagnostic and prophylactic applications.

Abstract: Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbonhydrate fragments each linked to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inparts enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from Streptococcus pneumoniae which may be serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F), or Neisseria meningitidis, which may be serotype (A, B, C) W-135 or Y. Such oligosaccharide fragments may be sized from about 2 to about 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, LeY or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule.

Abstract: In summary of this disclosure, the present invention provides certain novel alphavirus derived DNA vectors containing genes encoding RSV F or RSV G proteins, or other paramyxovirus proteins, methods of immunization using such vectors and methods of diagnosis using such vectors. Modifications are possible within the scope of this invention.

Abstract: Copolymers designed for use as particulate carriers containing functionalizable amino acid subunits for coupling with targeting ligands are described. The copolymers are polyesters composed of &agr;-hydroxy acid subunits such as D,L-lactide and pseudo-&agr;-amino acid subunits which may be derived from serine or terpolymers of D,L-lactide and glycolide and pseudo-&agr;-amino acid subunits which may be derived from serine. Stable vaccine preparations useful as delayed release formulations containing antigen or antigens and adjuvants encapsulated within or physically mixed with polymeric mircoparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody and protective responses.

Abstract: An isolated and purified outer membrane protein of a Moraxella strain, particularly M. catarrhalis, having a molecular mass of about 200 kDa, is provided. The about 200 kDa outer membrane protein as well as nucleic acid molecules encoding the same are useful in diagnostic applications and immunogenic compositions, particularly for in vivo administration to a host to confer protection against disease caused by a bacterial pathogen that produces the about 200 kDa outer membrane protein or produces a protein capable of inducing antibodies in a host specifically reactive with the about 200 kDa outer membrane protein.

Abstract: An isolated and purified outer membrane protein of a Moraxella strain, particularly M. catarrhalis, having a molecular mass of about 200 kDa, is provided. The about 200 kDa outer membrane protein as well as nucleic acid molecules encoding the same are useful in diagnostic applications and immunogenic compositions, particularly for in vivo administration to a host to confer protection against disease caused by a bacterial pathogen that produces the about 200 kDa outer membrane protein or produces a protein capable of inducing antibodies in a host specifically reactive with the about 200 kDa outer membrane protein.

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: Protective high molecular weight (HMW) proteins are produced recombinantly by expression from E. coli by using a promoter effective in E. coli and a nucleic acid molecule which contains a modified operon of a non-typeable strain of Haemophilus. The modified operon contains the portion only of the A region which encodes the mature HMW protein and the complete B and C regions of the operon. Enhanced levels of expression of the HMW proteins can be achieved by including the E. coli cer gene, a further copy of the portion of the A region of the operon encoding the mature protein or both in the expression vector. Nucleotide and deduced amino acid sequences of the hmw1 and hmw2 genes and HMW1 and HMW2 proteins, respectively of several non-typeable Haemophilus influenzae strain have been identified.

Abstract: Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Abstract: A gene from a strain of Mycobacterium encoding a protein of molecular weight between about 45 to about 60 kDa and associated with cell binding and cell entry was cloned. The genes and encoded protein have utility in immunogenic preparations or diagnostic applications.

Abstract: A modulated immune response to an antigen is achieved by coadministering the antigen and a genetically-detoxified pertussis holotoxin, particularly one retaining its immunogenicity, to a host. The modulated immune response enables immunogenic compositions, including multivalent pediatric vaccines, such as DTP, to be provided which produce a modulated immune response in the absence of extrinsic adjuvants, such as alum. The adjuvanting effect achieved by the genetically-detoxified pertussis holotoxin enables at least the same level of adjuvanting effect to be achieved as previously attained by alum, without the undesirable side effects thereof.

Abstract: Attenuated strains of Mycobacterium, particularly species of the tuberculosis complex, have the mycobacterial cell entry (mce) gene functionally disabled. The gene may be disabled by an insertion into the gene which disrupts the mycobacterial cell entry function thereof of a selectable marker which is used for screen for homologous recombinants in which a double cross-over event has been effected. The attenuated strains may be used in the immunization of hosts against Mycobacterium disease.

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: Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. 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. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.