Merck + Co., Inc.

Maurice R Hilleman

Philip J Provost

Eugene B Buynak

William J McAleer

Paula A Giesa

Allen F Woodhour

Oswald L Ittensohn

Richard L Tolman

William J Miller

Joseph Y Tai

William M Hurni

Arthur K Field

George P Lampson

Alfred A Tytell

Beverly J Neff

Philip P Vella

Hepatitis A virus is attenuated in virulence by in vitro passage in susceptible cell cultures, without prior passage in a subhuman primate. This process results in a live, attenuated hepatitis A virus vaccine suitable for human disease prevention.

Cell culture of hepatitis A virus

Hepatitis A virus is attenuated by propagation in cell culture in vitro by direct inoculation of the cell cultures with a human clinical specimen containing the virus.

Attenuated hepatitis A virus

Haemophilus influenzae type B polysaccharide is coupled through a spacer to a serotype outer membrane protein from Neisseria meningitidis. This conjugate has enhanced antigenicity and immunogenicity relative to the unconjugated polysaccharide.

Coupled H. influenzae type B vaccine

By serially passaging virulent parainfluenza virus in tissue culture prepared from embryonated hens' eggs or human diploid lung fibroblasts, a live, non-pathogenic but antigenic live parainfluenza virus is produced. This virus is useful in preparing a live virus vaccine.

Parainfluenza virus vaccine and its preparation

Hepatitis A virus is passaged at least once in a susceptible sub-human primate; the infected liver from such passage is used to inoculate an in vitro cell culture, the inoculated cell culture is incubated until hepatitis A antigen is detected in the cell sheet or culture fluid, and at least two serial in vitro passages in cell culture are carried out. The hepatitis A virus so modified can be used to prepare live, attenuated hepatitis A vaccine or an inactivated hepatitis A vaccine.

Hepatitis a virus cell culture in vitro

By serially passaging virulent respiratory syncytial virus in human diploid lung fibroblasts, a non-pathogenic but antigenic live respiratory syncytial virus is produced. This virus is useful in preparing a live virus vaccine.

Respiratory syncytial vaccine

Polynucleotides which are multistranded are active as inducers of interferon production in living animal cells. They may be:

Polynucleotides active as inducers of interferon production in living

Respiratory synctial vaccine

Pure isomannide monooleate and pure aluminum monostearate are used singularly or in combination in the preparation of emulsion type adjuvant vaccines to yield an adjuvant superior to prior art adjuvants which employ commercial mannide monooleate and aluminum monostearate. Highly desirable formulations are obtained by the inclusion of pure aluminum monostearate as a stabilizer in combination with the pure isomannide monooleate.

Water-in-oil adjuvant composition

Hepatitis A antigen obtained from the livers of non-human primates infected with hepatitis A (infectious hepatitis) virus has been found to be usable in fast, simple assays for hepatitis A antibody and thus usable in diagnosis of hepatitis A disease in humans, and for the preparation of hepatitis A vaccine.

Hepatitis A antigen

Vaccine delivery system having a lyophilized vaccine in human dosage concentration loaded into presterilized single dosage syringe having a squeezable body portion and a separate package containing enough water for injection to reconstitute the single dose of lyophilized vaccine.

Vaccine delivery system

Vaccine delivery system wherein an aqueous vaccine diluted to human dosage concentration is loaded into presterilized single dosage syringes having a squeezable body portion and wherein a plurality of these syringes are sealed inside a bag and the contents of the syringes are frozen to preserve the titer of the vaccine.

Syringe containing frozen vaccine

Hepatitis A antigen obtained from the stools of patients infected with hepatitis A (infectious hepatitis) virus has been found to be usable in fast, simple assays for hepatitis A antibody and thus usable in diagnosis of hepatitis A disease, and for the preparation of hepatitis A vaccine.

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Lafayette Hill, PA, United States of America

Maurice R Hilleman