Merck + Co., Inc.

N.v. Innogenetics S.a.

Margaret A Liu

John W Shiver

Donna Lorraine Montgomery

Helen C Perry

John J Donnelly

Jean Content

Daniel C Freed

Mary Ellen Davies

Jeffrey Ulmer

Kris Huygen

William L McClements

John A Lewis

Marcy E Armstrong

Robert D Keys

Tong-Ming Fu

Douglas Martinez

Genes encoding herpes simplex virus type 2 (HSV-2) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. In a DNA titration, it was found that a single immunization of &#x2267;0.5 &#x3bc;g of (one) PNV, gave &#x3e;90% seroconversion by ten weeks post immunization. Immune antisera neutralized both HSV-2 and HSV-1 in cell culture. When animals were challenged with HSV-2, significant (p&#x3c;0.001) protection from lethal infection was achieved following PNV vaccination. DNA constructs may be full-length, truncated and/or mutated forms and may be delivered along or in combination in order to optimize immunization and protection from HSV infection.

Polynucleotide herpes virus vaccine

Nucleic acids, including DNA constructs and RNA transcripts, capable of inducing coordinate expression of two to three cistrons upon direct introduction into animal tissues, are bi- or tri-cistronic polynucleotides of this invention include those encoding and co-expressing HIV gene products, genes encoding antigens unrelated to HIV, and immunostimulatory gene products, including but not limited to GM-CSF, interleukins, interferon and members of the B7 family of proteins which act as T-cell costimulatory elements. The methods and polynucleotides of this invention are generally applicable to co-ordinate expression in vivo of any two or more genes in a single cell.

Coordinate in vivo gene expression

Synthetic DNA molecules encoding HIV gag and modifications of HIV gag are provided. The codons of the synthetic molecules are codons preferred by the projected host cell. The synthetic molecules may be used as a polynucleotide vaccine which provides effective immunoprophylaxis against HIV infection through stimulation of neutralizing antibody and cell-mediated immunity.

Synthetic HIV gag genes

The present invention relates to polynucleotides comprising a DNA sequence encoding an HCV protein and fragments thereof that contain codons optimized for expression in a vertebrate host. Uses of the polynucleotides include eliciting an immune response specifically recognizing HCV.

Synthetic hepatitis C genes

Synthetic polynucleotides comprising a DNA sequence encoding a peptide or protein are provided. The DNA sequence of the synthetic polynucleotides comprise codons optimized for expression in a nonhomologous host. The invention is exemplified by synthetic DNA molecules encoding HIV env as well as modifications of HIV env. The codons of the synthetic molecules include the projected host cell's preferred codons. The synthetic molecules provide preferred forms of foreign genetic material. The synthetic molecules may be used as a polynucleotide vaccine which provides immunoprophylaxis against HIV infection through neutralizing antibody and cell-mediated immunity. This invention provides polynucleotides which, when directly introduced into a vertebrate in vivo, including mammals such as primates and humans, induces the expression of encoded proteins within the animal.

Vaccines comprising synthetic genes

Genes encoding ( ) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. Immune antisera was produced against antigens. Specific T-cell responses were detected in spleen cells of vaccinated mice and the profile of cytokine secretion in response to antigen 85 was indicative of a T 1 type of helper T-cell response (i.e., high IL-2 and IFN-&ggr;). Protective efficacy of an DNA vaccine was demonstrated in mice after challenge with BCG, as measured by a reduction in mycobacterial multiplication in the spleens and lungs of DNA-vaccinated mice compared to control DNA-vaccinated mice or primary infection in naive mice.

Polynucleotide tuberculosis vaccine

Polynucleotide vaccine for papillomavirus

Genes encoding Mycobacterium tuberculosis (M.tb) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. Immune antisera was produced against M.tb antigens. Specific T-cell responses were detected in spleen cells of vaccinated mice and the profile of cytokine secretion in response to antigen 85 was indicative of a T.sub.h 1 type of helper T-cell response (i.e., high IL-2 and IFN-.gamma.). Protective efficacy of an M.tb DNA vaccine was demonstrated in mice after challenge with M. bovis BCG, as measured by a reduction in mycobacterial multiplication in the spleens and lungs of M.tb DNA-vaccinated mice compared to control DNA-vaccinated mice or primary infection in naive mice.

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Rosemont, PA, United States of America

Margaret A Liu