Abstract: Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.

Abstract: This invention relates to attenuated pestiviruses characterised in that their enzymatic activity residing in glycoprotein ERNS is inactivated, methods of preparing, using and detecting these.

Abstract: The present invention provides an adjuvant for cancer antigen peptide vaccines and virus antigen peptides, containing a pertussis vaccine as a primary ingredient. The present invention also provides a therapeutic agent for a cancer or viral infectious disease, and a prophylactic agent for metastasis or recurrence of cancer or onset of virus-induced tumor, containing a cancer antigen peptide or virus antigen peptide and a pertussis vaccine. A pertussis vaccine that can be suitably used is a whole cell body pertussis vaccine. The agents of the present invention can be safely administered in a plurality of doses.

Abstract: The present invention relates to peptides and methods of inhibiting fusion between the virion envelope of Flaviviruses and membranes of the target cell, the process that delivers the viral genome into the cell cytoplasm. The invention provides for methods which employ peptides or peptide derivatives to inhibit Flavivirus:cell fusion. The present invention is based in part on the discovery that E1 envelope glycoprotein of hepaciviruses and E2 envelope glycoprotein of pestivirus have previously undescribed structures, truncated class II fusion proteins. The present invention provides peptides and methods of treatment and prophylaxis of diseases induced by Flaviviruses.

Abstract: The invention provides West Nile (WN) viruses and chimeric WN viruses having one or more mutations in the 3? terminal stem loop secondary structure (3?SL) that results in decreased neurovirulence, methods of making such WN viruses, and methods for using these WN viruses to prevent or treat WN virus infection.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus nonstructural proteins.

Abstract: Embodiments of the present invention report compositions and methods for vaccinating a subject against dengue viruses. In some embodiments, vaccine compositions may be administered by intradermal introduction. In certain embodiments, intradermal introduction in a subject of a vaccine against dengue virus may include one or more intradermal boosts after initial vaccination. Other embodiments include intradermal injection of a vaccine composition against dengue virus wherein the composition provides protection against two or more of DEN-1, DEN-2, DEN-3 and DEN-4.

Abstract: NS4B is one of the non-structural proteins of classical swine fever virus. By using functional genetics, we have discovered, in the predicted amino acid sequence of NS4B of CSFV strain Brescia, a motif that resembles those found in the toll-like receptor (TLR) proteins, a group of host cell proteins involved in the development of anti-viral mechanisms. We have located the TLR motif in two groups of amino acid triplets at amino acid positions 2531-3 (residues IYK) and 2566-8 (residues VGI) of the CSFV NS4B glycoprotein. We have constructed a recombinant CSFV (derived from an infectious clone containing the genetic information of the highly virulent strain Brescia) containing amino acid substitutions in the three amino acid residues at positions 2566, 2567 and 2568, where the VGI triplet has been replaced by an AAA triplet inside the NS4B glycoprotein. The obtained virus, named NS4B-VGIv, was completely attenuated in swine, showing a limited ability in spreading during the infection in vivo.

Abstract: The invention refers an improved vaccine against infections with pathogens, especially viral pathogens, comprising an antigen, a peptide of the formula R1—XZSZN—XZX—R2 and an immunostimulatory deoxynucleic acid containing deoxyinosine and/or deoxyuridine residues.

Abstract: The invention relates to a method for inducing a protection against the 4 dengue serotypes in a patient, comprising (a) a first series of administrations (i) of a dose of a vaccinal dengue virus of a first serotype and of a dose of a vaccinal dengue virus of a second serotype, and (ii) of a dose of a vaccinal dengue virus of a third serotype and of a dose of a vaccinal dengue virus of a fourth serotype, and (b) a second series of administrations of doses (i) and (ii), in which the doses (i) and (ii) are administered simultaneously at separate anatomical sites, and in which the second series (b) is implemented at least 30 days to at most 12 months after the first series (a).

Abstract: The present invention relates to combination vaccines and methods for treating or preventing diseases or disorders in an animal caused by infection by Bovine Viral Diarrhea Virus (BVDV) Types 1 and 2, Bovine Herpes Virus Type-1 (BHV-1), Bovine Respiratory Syncytial Virus (BRSV), Parainfluenza Virus (PI3), Campylobacter fetus, Leptospira canicola, Leptospira grippotyphosa, Leptospira hardj-prajitno, Leptospira icterohaemmorrhagiae, Leptospira hardjo-bovis and Leptospira pomona by administering to the animal an effective amount of a combination vaccine. The combination vaccine can be a whole or partial cell inactivated or modified live preparation.

Abstract: Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural viral proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural genes of a second flavivirus strain are inserted. These chimeric viruses elicit pronounced immunogenicity yet lack the accompanying clinical symptoms of viral disease. The attenuated chimeric viruses are effective as immunogens or vaccines and may be combined in a pharmaceutical composition to confer simultaneous immunity against several strains of pathogenic flaviviruses.

Abstract: The present invention features immunogenic compositions comprising codon modified genes that encode viral proteins and/or glycoproteins or fragments. The immunogenic compositions of the invention are useful in various methods of treatment, such as preventing or treating viral infection. Also provided in the present invention are kits and instructions for use.

Abstract: Immunogenic compositions comprising partially glycosylated viral glycoproteins for use as vaccines against viruses are provided. Vaccines formulated using mono-, di-, or tri-glycosylated viral surface glycoproteins and polypeptides provide potent and broad protection against viruses, even across strains. Pharmaceutical compositions comprising monoglycosylated hemagglutinin polypeptides and vaccines generated therefrom and methods of their use for prophylaxis or treatment of viral infections are disclosed. Methods and compositions are disclosed for influenza virus HA, NA and M2, RSV proteins F, G and SH, Dengue virus glycoproteins M or E, hepatitis C virus glycoprotein E1 or E2 and HIV glycoproteins gp120 and gp41.

Abstract: This invention provides pharmaceutical compositions, such as vaccines, and methods of making and using such compositions.

Abstract: Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (?-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.

Abstract: The present invention relates to a pharmaceutical composition containing an mRNA that is stabilised by sequence modifications in the translated region and is optimised for the translation. The pharmaceutical composition according to the invention is particularly suitable as an inoculating agent as well as a therapeutic agent for tissue regeneration. In addition a process is described for determining sequence modifications that serve for the stabilisation and translation optimisation of mRNA.

Abstract: The invention relates to a method for inducing protection against the 4 serotypes of dengue fever in a patient, comprising: (a) the administration of a monovalent vaccine comprising a vaccinal virus of a first serotype of dengue fever, and (b) the administration of a tetravalent vaccine comprising vaccinal viruses of the four serotypes of dengue fever, in which administration (b) is made between at least 30 days and not more than 12 months following the first administration (a).

Abstract: The present invention discloses the construction of dengue virus subgenomic replicons containing large deletions in the structural region (C-preM-E) of the genome, which replicons are useful as vaccines to protect against dengue virus infection.

Abstract: The present invention developed and characterized in vitro and in vivo three full-length cDNA clones based on the alphavirus chikungunya, two sets of infectious clones based on CHIKV and replicons based on the principle used to generate the infection clones. Described herein is the method to generate such infective clones and replicons, their composition and their use as molecular tool, a delivery vehicle and vaccine.

Abstract: The invention relates to building a chimeric polypeptide used for preventing or treating a Flaviviridae infection. The use of the inventive chimeric polypeptide for producing recombinant viral vectors such as a measles living viral vector is also disclosed.

Abstract: This invention describes a pharmaceutical compound which has the capsid protein of Dengue virus and which is capable of inducing, in the receptor, a protective immune response before the viral challenge, without inducing the Ab-dependent enhancement phenomenon.

Abstract: Live attenuated Eastern Equine Encephalitis (EEE) vaccines that outperform the PE-6 vaccine in mice aerosol challenged with >1,000×LD50. Candidates include four furin-cleavage deletion mutants and one E3 deletion mutant. Each vaccine provided protection in birds against antigenically distinct North and South American strains of EEE. The PE-6 vaccine does not provide protection against South American EEEs. Animals inoculated with each of the vaccines of the invention developed neutralizing antibodies to EEE.

Abstract: The present invention relates to an immunogenic composition. More particularly, the present invention is a composition directed to eliciting an immune response to at least one covalent binding site of myristate (SEQ ID NOS: 1-3) on the HIV matrix protein. The present invention contemplates three categories of embodiments: protein or protein fragments (SEQ ID NO: 1), messenger RNA, or DNA/RNA (SEQ ID NOS:2-3). DNA/RNA compositions may be either naked or recombinant. The present invention further contemplates use with a variety of immune stimulants.

Abstract: The invention relates to a method for inducing a homologous protection against the 4 dengue serotypes in a patient, comprising the sequential administration, to said patient, (i) of a dose of a vaccinal dengue virus of a first serotype and of a dose of a vaccinal dengue virus of a second serotype, and (ii) of a dose of a vaccinal dengue virus of a third serotype and of a dose of a vaccinal dengue virus of a fourth serotype, in which the vaccinal dengue viruses (ii) are administered at least 30 days and at most 1 year after administration of the vaccinal viruses (i).

Abstract: The present invention concerns methods and compositions involving flavivirus envelope protein domain III antigens for the detection of virus and detection of antibodies against the virus. Such methods and compositions may be used to detect TBE serocomplex viruses or West Nile virus infection in a subject, patient, animal or biological fluid. The present invention also concerns kits for implementing such methods. In some embodiments, kits contain a recombinant TBE serocomplex virus or West Nile virus envelope protein domain III antigen.

Abstract: The present invention relates to nine residue peptides (ApoptoM) from flavivirus M ectodomain able to modulate specifically the apoptotic activity of diverse flavivirus, to pharmaceutical composition comprising the same and their use for the treatment and/or the prevention of flavivirus-linked infections and cancers.

Abstract: The invention is a vaccine, and method of vaccination, against RNA viruses, including RNA viruses in the family Flaviviridae, which includes for example West Nile Virus, Yellow fever virus, Dengue fever virus, Hepatitis C virus, Pestiviruses, Bovine viral diarrhea virus, and Classical Swine fever virus, wherein the vaccine comprises the RNA virus or immunogenic portions thereof, which have been treated with and rendered non-pathogenic by a phenothiazine dye and visible light. The invention includes novel strains of WNV for use in producing a vaccine.

Abstract: The present invention relates to NS1 proteins or parts thereof of Flaviviruses, in particular of Dengue viruses useful for vaccination against said Flavivirus and against one or more other Flaviviruses. The invention further concerns the NS1 protein or parts thereof of one Dengue virus serotype, in particular serotype 2, useful for vaccination against Dengue viruses from all serotypes. The invention further concerns DNA comprising an expression cassette coding for a Flavivirus NS1 or parts thereof, vectors comprising said DNA and vaccines containing or expressing a Flavivirus NS1.

Abstract: The present invention provides safe vaccines and methods of preparing such vaccines. The vaccines of the present invention contain at least two live mutant viruses of the same family or nucleic acid molecules encoding such viruses, wherein each of the two viruses or the encoding nucleic acids contains a mutation that confers a desirable phenotype and the mutations in the viruses reside in the same genomic site such that the mutant viruses cannot recombine with each other to eliminate the mutations.

Abstract: This invention provides submicron oil-in-water emulsions useful as a vaccine adjuvant for enhancing the immunogenicity of antigens. The present invention also provides vaccine compositions containing an antigen combined with such emulsions intrinsically or extrinsically. Methods of preparing the emulsions and vaccines are also provided by the present invention.

Abstract: A nucleic acid molecule containing nucleotide sequences that encode the capsid protein, pre-membrane protein and non-structural protein of Japanese encephalitis virus, and a nucleotide sequence that encodes the envelop protein of a second flavivirus, wherein the nucleotide sequence(s) that encode(s) the pre-membrane protein and/or non-structural protein of Japanese encephalitis virus contain(s) nucleotide mutations that produce one or more amino acid mutations that attenuate the virus.

Abstract: A nasal vaccine is provided which induces the production of secretory IgA and IgG antibodies specific for flaviviruses, including hantaviruses. Furthermore, a method for providing protection against infection with flaviviruses by induces of the secretory IgA and IgG antibodies is also provided. The nasal vaccine includes an inactivated antigen of a flavivirus and poly(I:C) or a ceramified powder of surf clam shells as an adjuvant. The vaccine effectively induces secretion of IgA antibodies in the nasal mucosa and serum IgG antibody responses. Also provided is a method for inducing flavivirus-specific IgA and IgG antibodies, including administering an inactivated antigen of a flavivirus and poly(I:C) or a ceramified powder of surf clam shells as an adjuvant to the mucosa of a respiratory tract.

Abstract: An immunogenic or vaccine composition to induce an immune response or protective immune response against West Nile virus (WNV) in an animal susceptible to WNV. The composition includes a pharmaceutically or veterinarily acceptable vehicle or excipient, and a vector. The vector contains heterologous nucleic acid molecule(s), expresses in vivo in the animal WNV antigen, immunogen or epitope thereof, e.g., WNV E; WNV prM and E; WNV M and E; WNV prM, WNV M and E, WNV polyprotein prM-E, WNV polyprotein M-E, or WNV polyprotein prM-M-E. The composition can contain an adjuvant, such as carbomer. Methods for making and using such a composition, including prime-boost regimes and including as to differential diagnosis, are also contemplated.

Abstract: The present invention relates to chimeric pestiviruses having utility as immunogenic compositions and vaccines. Also described herein are methods and kits for treating or preventing the spread of bovine viral diarrhea virus infection, as well as methods and kits for differentiating between vaccinated and wild-type infected animals.

Abstract: The present invention relates to NS1 proteins or parts thereof of Flaviviruses, in particular of Dengue viruses useful for vaccination against said Flavivirus and against one or more other Flaviviruses. The invention further concerns the NS1 protein or parts thereof of one Dengue virus serotype, in particular serotype 2, useful for vaccination against Dengue viruses from all serotypes. The invention further concerns DNA comprising an expression cassette coding for a Flavivirus NS1 or parts thereof, vectors comprising said DNA and vaccines containing or expressing a Flavivirus NS1.

Abstract: The invention includes a genetic construct and a mutant dengue virus, designated as strain MBU 01-2002, which is a mutant dengue virus generated by genetic modification of the 13-amino acid sequence just proximal to the pr-M junction within the prM coding region of the genome. The modification involves increasing the number of positively charged amino acids and abolishing the negatively charged amino acids in this pr-M junction sequence. The mutant dengue virus strain MBU 01-2002 possesses less prM protein on the viral envelope than the prototype dengue virus, is capable of inducing infected C6/36 cells to fuse at neutral pH, is as efficient as the prototype virus in the intracellular multiplication, but is defective in its release from infected cells.

Abstract: The invention relates to a method for inducing a protection against the 4 dengue serotypes in a patient, comprising (a) a first series of administrations (i) of a dose of a vaccinal dengue virus of a first serotype and of a dose of a vaccinal dengue virus of a second serotype, and (ii) of a dose of a vaccinal dengue virus of a third serotype and of a dose of a vaccinal dengue virus of a fourth serotype, and (b) a second series of administrations of doses (i) and (ii), in which the doses (i) and (ii) are administered simultaneously at separate anatomical sites, and in which the second series (b) is implemented at least 30 days to at most 12 months after the first series (a).

Abstract: The invention relates to a method for inducing a homologous protection against the 4 dengue serotypes in a patient, comprising the sequential administration, to said patient, (i) of a dose of a vaccinal dengue virus of a first serotype and of a dose of a vaccinal dengue virus of a second serotype, and (ii) of a dose of a vaccinal dengue virus of a third serotype and of a dose of a vaccinal dengue virus of a fourth serotype, in which the vaccinal dengue viruses (ii) are administered at least 30 days and at most 1 year after administration of the vaccinal viruses (i).

Abstract: The invention relates to a method for inducing protection against the 4 serotypes of dengue fever in a patient, comprising: (a) the administration of a monovalent vaccine comprising a vaccinal virus of a first serotype of dengue fever, and (b) the administration of a tetravalent vaccine comprising vaccinal viruses of the four serotypes of dengue fever, in which administration (b) is made between at least 30 days and not more than 12 months following the first administration (a).

Abstract: E2 is one of the three envelope glycoproteins of Classical Swine Fever Virus (CSFV). E2 is involved in several functions including virus attachment and entry to target cells, production of antibodies, induction of protective immune response in swine, and virulence. Seven putative glycosylation sites in E2 were modified by site directed mutagenesis of a CSFV Brescia infectious clone (BICv). A panel of virus mutants was obtained and used to investigate whether the removal of putative glycosylation sites in the E2 glycoprotein would affect viral virulence/pathogenesis in swine. We observed that rescue of viable virus was completely impaired by removal of all putative glycosylation sites in E2, but restored when mutation N185A reverted to wild-type asparagine produced viable virus that was attenuated in swine. Single mutations of each of the E2 glycosylation sites showed that amino acid N116 (N1v virus) was responsible for BICv attenuation.

Abstract: The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3? untranslated region (3?-UTR) comprising a ?30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the ?30 mutation deleted from the 3?-UTR that removes sequence in the 5? direction as far as the 5? boundary of the TL-3 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, or a replacement of the 3?-UTR of a dengue virus of a first serotype with the 3?-UTR of a dengue virus of a second serotype, optionally containing the ?30 mutation and nucleotides additional to the ?30 mutation deleted from the 3?-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

Abstract: Disclosed herein are methods of modulation of the viability of a cell. Further disclosed herein are methods of modulating an immune response. Further disclosed herein are methods of identifying agents capable of modulation of the viability of a cell or an immune response. Further disclosed herein are agents and compositions capable of modulation of the viability of a cell or an immune response.

Abstract: The invention concerns a method for early detection of a flavivirus-induced infection, comprising the detection of the flavivirus non-structural glycoprotein NS1 in a biological sample during the clinical phase of the infection, by an immunological method using at least two identical or different antibodies, the first antibody consisting of polyclonal or monoclonal antibodies pre-selected for their high affinity for said NS1 protein hexameric in shape.

Abstract: Briefly described, virosomes, methods of preparing virosomes, immunogenic compositions that include virosomes, and methods of eliciting an immune response using immunogenic compositions that include virosomes are described herein. A virosome can include at least one viral surface envelope glycoprotein expressed on the surface of the virosome. The virosome can also optionally include at least one adjuvant molecule expressed on the surface of the virosome.

Abstract: The present invention relates to NS1 proteins or parts thereof of Flaviviruses, in particular of Dengue viruses useful for vaccination against said Flavivirus and against one or more other Flaviviruses. The invention further concerns the NS1 protein or parts thereof of one Dengue virus serotype, in particular serotype 2, useful for vaccination against Dengue viruses from all serotypes. The invention further concerns DNA comprising an expression cassette coding for a Flavivirus NS1 or parts thereof, vectors comprising said DNA and vaccines containing or expressing a Flavivirus NS1.

Abstract: The present invention encompasses isolated nucleic acids containing transcriptional units which encode a signal sequence of one flavivirus and an immunogenic flavivirus antigen of a second flavivirus or of a chimeric immunogenic flavivirus antigen comprising sequence from more than one flavivirus. The invention further encompasses a nucleic acid and protein vaccine and the use of the vaccine to immunize a subject against flavivirus infection. The invention also provides antigens encoded by nucleic acids of the invention, antibodies elicited in response to the antigens and use of the antigens and/or antibodies in detecting flavivirus or diagnosing flavivirus infection.

Abstract: A glycoprotein E2 of classical swine fever virus (CSFV) expressed in a recombinant yeast system. The recombinant E2 protein (yE2) is able to form a homodimer, exhibits glycosylation conformation and possesses correct immunogenicity. An anti-CSFV vaccine can be provided with yE2 as a major active ingredient to induce high titers of neutralizing antibody in vaccinated pigs, and to induce a protection against CSFV infection.

Abstract: Methods of eliciting humoral responses, methods of immunization, and methods of vaccination using lentiviral vector are disclosed. Additionally, immunogenic compositions and vaccines for West Nile Virus are disclosed.

Abstract: A prophylactic or therapeutic vaccine for use in protecting mammals such as humans or animals against Venezelan Equine Encephalitis virus (VEE) is described. In particular, the vaccine comprises a recombinant virus such as a recombinant vaccinia virus which is able to express the structural genes of VEE in attenuated form, which has been modified to increase the protective effect of the vaccine. This is achieved by modifying the sequence of the attenuated VEE strain and/or putting this under the control of modified promoter which increases expression from the vector. Formulations of the vaccine as well as methods of treatment using the vaccine are also described.