Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Emilio A Emini

Andrew J Bett

John W Shiver

David C Kaslow

Joshua S Boger

Stefano Colloca

Alfredo Nicosia

Riccardo Cortese

Armin Lahm

Ling Chen

Danilo R Casimiro

Alessandra Luzzago

Richard L Tolman

William J Leanza

Stephen Marburg

Michael P Caulfield

Vivian M Larson

Joseph V Hughes

Jeffrey A Chodakewitz

John A Lewis

Marcy E Armstrong

Rima Youil

Timothy J Toner

Michael A Chastain

The present invention features Ad6 vectors and a nucleic acid encoding a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide containing an inactive NS5B RNA-dependent RNA polymerase region. The nucleic acid is particularly useful as a component of an adenovector or DNA plasmid vaccine providing a broad range of antigens for generating an HCV specific cell mediated immune (CMI) response against HCV.

Hepatitis C virus vaccine

An adenoviral vector is described which carries a codon-optimized gag gene, along with a heterologous promoter and transcription terminator. This viral vaccine can effectively prevent HIV infection when administered to humans either alone or as part of a prime and boost regime also with a vaccine plasmid.

Adenovirus carrying gag gene HIV vaccine

First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-gag, pol, nef and modifications

The combination of the HIV protease inhibitor Compound J, 3TC, and, optionally AZT, ddI, or ddC, is useful in the inhibition of HIV protease, the inhibition of HIV reverse transcriptase, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Combination therapy for HIV infection

A novel coconjugate comprising an immunogenic protein or protein complex having a first set of covalent linkages to low molecular weight moieties, --a.sup.--, which have an anionic or polyanionic character at physiological pH, and a second set of covalent linkages to peptides comprising Human Immunodeficiency Virus (HIV) Principal Neutralizing Determinants (PNDs), or peptides immunologically equivalent therewith, is useful for inducing anti-peptide immune responses in mammals, for inducing HIV-neutralizing antibodies in mammals, for formulating vaccines to prevent HIV infection or disease, including the Acquired Immune Deficiency Syndrome (AIDS), or for treating humans afflicted with HIV infection or disease.

Coconjugates of OMPC, HIV related peptides and anionic moieties

New methods for purifying Hepatitis A virus (HAV) are to commercial scale-up and manufacture of specific HAV vaccines, including formalin-inactivated HAV and attenuated HAV.

Novel process for purification of hepatitis a virions

A synthetic peptide, containing the predicted amino acid residues 64 to 77 of the herpes simplex virus type 1 (HSV1) gB structural glycoprotein open reading frame, a synthetic subunit immunogen that stimulates an immune response against HSV1 and which, when prepared, and chemically-conjugated to a protein carrier molecule, and inoculated into test animals, gives rise to a specific anti-peptide IgG response, such that these anti-peptide antibodies react with a purified HSV-specific structural glycoprotein preparation and are capable of neutralizing the infectivity of HSV1.

Immunogenic synthetic peptide capable of eliciting herpes simplex virus

Synthetic peptides, containing amino acid residues 15 to 21, 75-80 and 101-107 of the hepatitis A virus (HAV) VP1 structural protein sequence, was prepared and chemically conjugated to a protein carrier molecule. The peptide-carrier conjugate, when inoculated into test animals, gives rise to a specific anti-peptide IgG antibody response. These anti-peptide antibodies bind directly to intact hepatitis A virions, bind to purified and denatured VP1, compete with polyspecific antibody derived from human HAV immune sera, and are capable of neutralizing the infectivity of the virus. The peptide is useful as a synthetic subunit immunogen that stimulates an immune response against HAV.

Immunogenic HAV peptides

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Wayne, PA, United States of America

Emilio A Emini