Merck + Co., Inc.

Arpi Hagopian

Peter J Kniskern

Dennis J Carlo

Pamela D Burke

William J Miller

Ronald W Ellis

Thomas H Stoudt

Dennis J Kubek

Charlotte C Ip

John P Hennessey

Richard L Tolman

Stephen Marburg

Donna Lorraine Montgomery

John P Hennessey Jr

Type-specific capsular polysaccharide preparations from Streptococcus pneumoniae, having on average less than about 1000 oligosaccharide repeat units per molecule, polydispersities between 1.0 and 1.4, intrinsic viscosities between 0.6 and 3.0 dL/g, and less than 3% contamination of type-specific polysaccharide by group-specific C-polysaccharide, are produced by a novel process. The novel type specific polysaccharide products are useful in the preparation of vaccines, especially covalent conjugates comprising the novel polysaccharide linked to a T-cell stimulatory carrier protein. Vaccines comprising the novel polysaccharides are useful in the prevention of infection and of diseases associated with infection by Streptococcus pneumoniae.

Process for making capsular polysaccharides from Streptococcus

A novel conjugate vaccine comprising partially hydrolyzed, highly purified, capsular polysaccharide (Ps) from Streptococcus pneumoniae bacteria (pneumococci, Pn) linked to an immunogenic carrier protein, is produced by a new process. The conjugate is useful in the prevention of pneumococcal infections. Vaccines comprising a mixture of from one to ten different pneumococcal polysaccharide-immunogenic protein (Pn-Ps-PRO) conjugates induce broadly protective recipient immune responses against the cognate pathogens from which the polysaccharide components are derived. Young children and infants younger than 2 years old, normally unable to mount a protective immune response to the Pn-Ps alone, exhibit protective immune responses upon vaccination with these Pn-Ps-PRO conjugates.

Pneumococcal polysaccharide conjugate vaccine

In order to produce hepatitis B virus (HBV) surface proteins in the form of particles with substantially reduced entrapped carbohydrate content, DNA encoding the HBV surface proteins was expressed in a recombinant yeast host which is deficient in its ability to glycosylate proteins. These HBV surface proteins display the antigenie sites genetically encoded by the S domain of the HBV virion envelope open reading frame and contains substantially reduced levels of entrapped carbohydrate when compared with HBsAg particles produced in 'wild-type' yeast cells. These particles are useful as a vaccine for both the active and passive treatment or prevention of disease and/or infection caused by HBV or other agents serologically related to HBV.

Hepatitis B virus surface proteins with reduced host carbohydrate content

The present invention relates to recombinant fusion polypeptides of HIV envelope and HBsAg, suitable as vaccines against AIDS and/or ARC and hepatitis, as well as immunogens for inducting antibodies for passive protection or treatment of AIDS and/or ARC.

Expression of fusion protein of HIV envelope and HBsAG

The present invention relates to recombinant fusion polypeptides of HIV envelope and HBsAg, suitable as vaccines against AIDS and/or ARC and hepatitis, as well as immunogens for inducing antibodies for passive protection or treatment of AIDS and/or ARC.

Expression of fusion protein of HIV envelope and HBsAg

The hepatitis B virus preS2 antigen gene linked in one contiguous reading frame to the hepatitis B virus surface antigen gene has been expressed in Saccharomyces cerevisiae utilizing an optimized plasmid construction. The expressed protein aggregates into a particulate form which displays the major antigenic sites encoded by both domains, thereby highlighting the utility of yeast as a host for the high level expression of the preS2 as well as the S domain. This protein is useful in in vitro diagnostic systems and as a vaccine for the treatment and prevention of hepatitis B virus-induced diseases and/or infections.

Method for producing hepatitis B virus proteins in yeast

The entire hepatitis B Virus pre-S antigen gene linked in one contiguous reading frame to the hepatitis B virus surface antigen gene has been expressed in Saccharomyces cerevisiae. The expressed protein aggregates into a particulate form which displays the major antigenic sites encoded by both domains, thereby highlighting the utility of yeast as a host for the expression of pre-S domains. This protein is useful in in vitro diagnostic systems and as a vaccine for the treatment and prevention of hepatitis B virus-induced diseases and/or infections.

A high molecular weight capsular polysaccharide from H. influenza type b is an effective immunogenic agent against infection caused by the H. influenza type b bacterium.

Meningitis vaccine

A sub-cellular antigenic fraction of Bordetella bronchiseptica protects against the incidence and severity of swine atropic rhinitis.

Method of obtaining an antigenic fraction from Bordetella bronchiseptica

A vaccine against Group C meningococcal meningitis consisting of a polysaccharide of which at least 80% by weight has a molecular weight in excess of 1,000,000 daltons is prepared. The polysaccharide was isolated from Group C hexadecyl trimethylammonium bromide cell paste with 1.0M CaCl.sub.2 extraction and purified by phenol extraction, ultracentrifugation at 100,000 g. and ethanol fractionation (30%-45% v/v in ethanol).

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Lansdale, PA, United States of America

Arpi Hagopian