National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

National Institutes of Health

Dyncorp

The United States of America As Represented by the Secretary of

Albert Z Kapikian

Robert M Chanock

Yasutaka Hoshino

Robert H Purcell

Richard G Wyatt

Louis Potash

Karen Midthun

Jorge Flores

Timo Vesikari

Harry B Greenberg

Anthony R Kalica

Brian R Murphy

Linda J Saif

Walter D James

Edward H Bohl

David M Morens

Kenneth W Theil

John R La Montagne

Mary Elaine La Montagne, Legal Representative

Mario Gorziglia

Lone Simonsen

Irene Peres-Schael

The present invention provides vaccine compositions for protection against human rotaviral disease designed for use in particular areas of the world. Human&#xd7; bovine reassortant rotavirus comprising each of the four clinically most important VP7 serotypes of human rotavirus are combined with other VP7 serotypes typically found in the area of interest into a multivalent formulation which provides a high degree of infectivity and immunogenicity. Methods and an administration protocol for producing an immunogenic response without producing an increased risk of intussusception are also provided.

Hexavalent bovine rotavirus reassortant composition designed for use in developing countries

The present invention provides vaccine compositions for protection against human rotaviral disease without significant reactogenicity. Human&#xd7;bovine reassortant rotavirus comprising each of the four clinically most important VP7 serotypes of human rotavirus are combined in a multivalent formulation which provides a high degree of infectivity and immunogenicity without producing a transient febrile condition. Methods for producing an immunogenic response without producing a transient febrile condition are also provided.

Multivalent human-bovine rotavirus vaccine

The present invention provides compositions for making a medicament and methods for the administration of a vaccine compositions for protection against human rotaviral disease without significant reactogenicity. Human x rhesus reassortant rotavirus compositions were made which when administered during the first 7 to about 10 days of life, provided a composition which was non-reactogenic followed by booster immunizations at 16 to 18 weeks or 14 to 20 weeks, up to 1 year of age. The immune response induced by the initial neonatal administration of the live rotavirus vaccine composition protects the infant from the reactogenicity of the composition when administered as a second vaccine dose at or after 2 months of age. Administration of the immunogenic composition also is expected to ablate or significantly diminish the increase in the excess of intussusception observed 3 to 7 days following administration of the initial dose of rotavirus vaccine at about 2 to 4 months.

Compositions and method for preventing reactogenicity associated with administration of immunogenic live rotavirus compositions

The present invention provides vaccine compositions of attenuated human rotavirus. More particularly, the attenuated human rotavirus is produced by cold passage and thus contains attenuating mutations which produce virus having a cold-adapted (ca) and temperature sensitive (ts) phenotype. The attenuated strains are used in methods for stimulating the immune system of an individual to induce protection against human rotavirus by administration of the ca attenuated rotavirus.

Attenuated human rotavirus vaccine

The invention described herein provides a method for selecting a novel African Green monkey kidney (AGMK) cell substrate, its cultivation and serial passage and its subsequent characterization. The invention provides a method for the use of the cell substrate in the isolation, growth and serial passage of a large number of viruses, particularly rotaviruses, enteroviruses, respiratory viruses and hepatitis A virus. The invention provides a method for the utilization of this AGMK cell substrate for the production of live and killed virus vaccines.

Method for producing an adapted virus population from an African green

A method for producing novel African Green Monkey Kidney (AGMK) cell lines is taught. These cell lines which are free of viable adventitious microbial agents are useful as substrates for viruses and for the preparation of viral vaccines.

Method for producing a virus from an african green monkey kidney cell

Method of producing a virus vaccine from an African green monkey kidney

A novel African Green Monkey Kidney (AGMK) cell line is taught as well as a method for the preparation thereof. The cell line which is free of viable adventitious microbial agents is useful as a substrate for viruses and for the preparation of viral vaccines.

African green monkey kidney cell lines useful for maintaining viruses

A new method for producing live, attenuated rotavirus strains suitable for preparing a vaccine is described. It is demonstrated that a naturally attenuated rotavirus recovered from newborns or other individuals whos have undergone asymptomatic infection can be used for immunization or that a virulent rotavirus can be converted into an attenuated strain by substituting the conserved fourth rotavirus gene segments of a naturally attenuated rotavirus in the genome of the virulent rotavirus.

Vaccine against rotavirus diseases and method of preparing same

The present invention discloses a vaccine for the prevention of rotavirus caused diseases in humans. The vaccine is prepared from attenuated, immunogenic rhesus rotavirus which has been characterized to be antigenically similar, if not identical, to human rotavirus serotype 3.

Vaccine against rotavirus diseases

This invention relates to processes which are used to produce, isolate, and characterize human rotavirus/animal rotavirus reassortants and to produce live attenuated vaccines and vaccine precursors. In the present strategy there is involved the new use of either (1) high titer hyperimmune antisera or (2) monoclonal antisera to select reassortants with the desired human phenotype. A point of novelty is the finding that antiserum or monoclonal antisera alone, so long as it possesses high titer neutralizing activity against only the 34-38Kd glycoprotein or of the animal parent, is sufficient to use for selection of reassortant rotaviruses with human phenotype. Also, the novel products are live attenuated vaccine precursors and vaccines.

Genetic reassortment of rotaviruses for production of vaccines and

This invention relates to a precursor or intermediate for a rotavirus vaccine to protect infants and young children against diarrhea caused by rotavirus. The invention is the efficient propagation of a strain of human rotavirus type 2 prepared by a method of cultivation by multiple passages in vivo in gnotobiotic piglets and by multiple passages in vitro subsequently in AGMK (African green monkey kidney) cell cultures. Additionally, rotavirus is treated with a biologically active amount of trypsin prior to growth in AGMK cells, and the inoculated cell cultures are centrifuged at a low centrifugal force before incubation.

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Rockville, MD, United States of America

Albert Z Kapikian