Title:  Cross-protective rotavirus vaccine

United States Patent:  6,187,319

Assignee:  University of Massachusetts (Boston, MA)

Filed:  June 1, 1998

A method of producing an effective immune response in an animal against a first rotavirus, by (1) identifying an animal susceptible to or having a first rotavirus infection; and (2) administering 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.

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.

Claim 1 of 27 Claims

What is claimed is:

1. A method of producing a protective immune response in a bird or mammal against a first rotavirus, the method comprising:

identifying a bird or mammal susceptible to or having a first rotavirus infection;

administering to the bird or mammal an isolated VP6 polypeptide of a second rotavirus sufficient to produce a protective immune response against the first rotavirus, the second rotavirus capable of infecting a different species than the first rotavirus.

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