Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Reexamination Certificate
1998-06-01
2001-02-13
Caputa, Anthony C. (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
C514S04400A
Reexamination Certificate
active
06187319
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to rotavirus vaccines.
Rotavirus infections are ubiquitous throughout mammalian and avian species. The viruses typically appear to be species-specific in the wild. Infection occurs after ingestion of viral particles and is restricted to the mature absorptive epithelial cells on the villi of the small intestine. Multiplication of rotaviruses within these cells results in lysis, and eventual loss of normal villous structure. Copious acute watery diarrhea occurs as a result of intestinal damage and replacement of absorptive cells by secreting cells from the villous crypts in the intestine.
Rotaviruses have a multi-shelled capsid and a segmented RNA genome. Among the rotavirus structural proteins are VP7, the most abundant outer capsid protein in the virus particle, and VP6, the major component of the inner capsid.
SUMMARY OF THE INVENTION
The invention is based on the discovery that an isolated VP6 polypeptide from a rotavirus which naturally infects one species (such as a cow) can produce an effective immune response against a rotavirus which naturally infects another species (such as a mouse or human), so that VP6 is an effective cross-protective rotavirus vaccine. An isolated VP6 polypeptide is a VP6 polypeptide that is in an environment other than its natural environment, e.g., by purification or simply as a result of enhancing the percentage of VP6 present (“spiking”) in naturally occurring mixtures such as viral or infected cell preparations.
In general, the invention features a method of producing an effective immune response in an animal (for example, cows, pigs, horses, and especially humans) against a first rotavirus by (1) identifying an animal susceptible to or having a first rotavirus infection; and (2) administering (e.g., orally) to the animal an isolated VP6 polypeptide of a second rotavirus sufficient to produce an effective immune response against the first rotavirus, the second rotavirus capable of infecting a different species than the first rotavirus. For example, a cow, pig, or horse rotavirus VP6 is administered to a human in order to elicit an effective immune response against a human rotavirus. Alternatively, a human, cow, or pig rotavirus VP6 is administered to a horse in order to elicit an effective immune response against a horse rotavirus. In addition, the VP6 polypeptide can cross-react with antibodies produced from the animal (e.g., a human) when infected with the first rotavirus (e.g., a human rotavirus).
In some embodiments of the above method, the animal is of a first species, and the second rotavirus is capable of infecting a second species different from the first species and incapable of infecting the first species.
An immune response against the first rotavirus is considered effective if viral loads or the symptoms of infection are reduced in the animal when the VP6 is administered to the animal as compared to when the VP6 is not administered. Preferably, such reductions are statistically significant, as shown in the Example section below. For example, an immune response that protects against viral infection is “effective.”
The isolated VP6 polypeptide of the second rotavirus can be administered to the animal via an expression vector (e.g., a DNA plasmid) comprising a sequence encoding the VP6 polypeptide of the second rotavirus. When the isolated VP6 is administered as a DNA plasmid, DNA delivery can be facilitated by encapsulating the DNA in a microparticle, e.g., one made of poly(lactide-co-glycolide) (PLG).
An expression vector encoding the isolated VP6 polypeptide is not limited to a DNA plasmid. For example, an expression vector can be a virus, such as a retrovirus. Whether in the form of a plasmid or virus, the expression vector can further contain a cytomegalovirus intron A transcriptional regulatory sequence and a cytomegalovirus enhacer and promoter sequence operably linked to the sequence encoding the VP6 polypeptide of the second rotavirus.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although suitable methods and materials for the practice or testing of the present invention are described below, other methods and materials similar or equivalent to those described herein, which are well known in the art, can also be used. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.
REFERENCES:
patent: 5620896 (1997-04-01), Hermann et al.
Andrew et al., “The Roles of Influenza Virus Haemagglutinin an Nucleoprotein in Protection: Analysis Using Vaccinia Virus Recombinants”, Scand. J. Immunol. 25:21-28, 1987.
Conner et al., “Rotavirus Vaccines and Vaccination Potential”, Current Topics in Microbiology and Immunology 185:297-305, 1994.
Dharakul et al., “Immunization with Baculovirus-Expressed Recombinant Rotavirus Proteins VP1, VP6, and VP7 Induces CD8+ T Lymphocytes . . . ”, J. of Virology 5928-5932, 1991.
Herrmann et al., “DNA Vaccines Against Rotavirus Infections”, Arch Virol Suppl. 12:207-215, 1996.
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Herrmann John E.
Lu Shan
Brumback Brenda G.
Caputa Anthony C.
Fish & Richardson P.C.
University of Massachusetts
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