Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or...
Patent
1998-07-28
2000-08-29
Mosher, Mary E.
Chemistry: molecular biology and microbiology
Virus or bacteriophage, except for viral vector or...
435364, 4242151, C12N 700, A61K 3915
Patent
active
061107247
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to rotavirus antigens of which the mass production via cell culture are difficult, a vaccine against rotavirus infections and a diagnostic agent of the diseases and methods for producing the same. More specifically, the present invention relates to a vaccine and a diagnostic agent useful for the prophylaxis and diagnosis of rotavirus infections, and rotavirus antigens as the effective ingredient thereof. The present invention makes contributions to the prophylaxis and diagnosis of rotavirus infections in humans, in particular.
2. Description of the Related Art
Rotavirus is a pathogenic microorganism causing diarrhea in humans, monkeys, dogs, cats, horses, cows, pigs, sheep, rabbits, rats, chickens, turkeys and the like, and is widely distributed all around the world. Rotavirus infections in humans in particular have been drawing attention, as vomiting and diarrhea in babies, winter-term diarrhea in babies, diarrhea with white feces, kid pseudo-cholera and the like. The prophylaxis and diagnosis thereof have been expected strongly at a worldwide scale.
What will be described below has been known concerning rotavirus.
According to the 6-th report by the International Committee of Taxonomy of Viruses, the virus belongs to the family Reoviridae, and is in an exact icosahedron of a diameter of about 70 nm, comprising a double capsid structure of inner and outer capsids (three layers in total, including the intermediate layer) with no envelop, and has a core of a diameter of about 50 nm at the center of the inner capsid. Inside the core is present a genome, comprising a linear double-stranded RNA with 11 segments, and the sizes of these genome segments are within a range of 0.6 to 3.3 kbp ("Virus Taxonomy: Sixth Report of the International Committee of Taxonomy of Viruses", Archives of Virology, Supplement 10, pp.219-222, 1995).
From the standpoint of developing a vaccine and a diagnostic agent therefor, attention has been focused particularly on the fourth genome segment and the ninth genome segment (corresponding to the seventh or eighth genome segment in some strain), among the 11 genome segments described above. Rotavirus strains isolated worldwide have been classified into six groups (serogroups) from A to F and each group is divided into various serotypes; for convenience, additionally, rotavirus strains are broadly grouped depending on the genotypes. These isolated strains have a variety of both antigenicities and genotypes ("Fields Virology", 3rd ed., vol.12, pp.1625-1629, edited by B. N. Fields et al., Lippincott-Raven Publishers, 1996, USA). The following description is about what is described immediately above.
The fourth genome segment encodes the structure protein VP4 exposed in a spike form on the surface of the virus particle, and it is reported or assumed that VP4 may functionally be involved in blood cell agglutinins, neutralizing antigens, the infectivity promoted by protease, pathogenicity, membrane fusion, adsorption to cells, and so on. Based on the amino acid sequence of the VP4 and the homology with the RNA or cDNA of the gene, rotavirus stains are currently classified into 20 genotypes (referred to as "P genotype" hereinbelow); and based on the neutralizing test, rotavirus strains are also classified into 10 or 14 serotypes (referred to as "Serotype P" hereinbelow).
The ninth genome segment (seventh or eighth genome segment in some strain) encodes the outer capsid VP7 of the virus particle, and it is reported or assumed that the VP7 may possibly function to retain the epitope of neutralizing antigen and two hydrophobic regions. Based on the neutralizing test of the VP7, rotavirus strains are classified into 14 serotypes (referred to as "serotype G" hereinbelow).
Among a great number of various isolated strains reported previously ("Fields Virology", 3rd ed., vol.2, p.1627), a typical human rotavirus strain of the group A and the following strains isolated and reported by the present inventors, namely AU-1
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Imagawa Tadashi
Murakami Shigeki
Nakagomi Osamu
Nakagomi Toyoko
Mosher Mary E.
The Research Foundation For Microbial Diseases of Osaka Universi
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