Merck + Co., Inc.

E Dale Lehman

Kathrin Ute Jansen

William J McAleer

Michael P Neeper

Joseph G Joyce

Kathryn J Hofmann

Hugh A George

Vivian M Larson

Ted F Schaefer

Edward M Scolnick

Robert S Lowe

D Eugene Wampler

Arthur Friedman

Synthetic HPV6/11 hybrid L1 DNA encoding human papillomavirus type 11 L1

The present invention is directed to a recombinant human papillomavirus type 11 L1 protein encoded by a synthetic DNA molecule and methods of making and using the protein.

Production of recombinant human papillomavirus type II protein utilizing

Recombinant pre-S-HBsAg is purified by a rapid and efficient two step chromatographic process. Yeast cells expressing recobinant pre-S-HBsAg are disrupted, the cell contents are clarified and separated by polymerized human serum albumin affinity chromatography. The pre-S-HBsAg is further purified by hydrophobic interaction chromatography using butyl agarose. This process results in pre-S-HBsAg that is greater than 90% pure.

Purification of hepatitis pre-S antigens by polymerized serum albumin

The surface antigen protein of human Hepatitis B virus is synthesized in Saccharomyces cerevisiae as a 23,000-26,000 dalton polypeptide, essentially free of intermolecular disulfide bonds. This antigen is a poor immunogen in animals and man. No prior precedent or method exists for efficiently converting the non-disulfide bonded antigen to a fully intermolecular disulfide bonded particle. We describe the first example of such a conversion in vitro and show that the act of this conversion enhances the immunogenicity of the antigen about 10-fold. The in vitro conversion makes practical the production of hepatitis B surface antigen from microorganisms using recombinant DNA methods.

Immunogenic HbsAg derived from transformed yeast

Herpes virus subunit antigens suitable for vaccine use are prepared by (1) treating virus-infected cells with a surfactant and varying concentrations of salt to extract and solubilize viral-directed glycoproteins, (2) fractionating the solubilized material by chromatographic procedures to enrich the viral-directed glycoproteins and to remove unwanted proteins and nucleic acids, and (3) optionally treating the subunit antigens with deoxyribonuclease and formaldehyde to assure safety.

Herpes subunit vaccine

Herpes sub unit vaccine

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Lansdale, PA, United States of America

E Dale Lehman