Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Parasitic organism or component thereof or substance...
Reexamination Certificate
2001-09-12
2003-12-02
Smith, Lynette R. F. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Parasitic organism or component thereof or substance...
C424S271100, C424S273100, C424S093200, C424S093100, C424S258100, C435S069100, C435S258100, C800S281000
Reexamination Certificate
active
06656479
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to attenuated strains of the pathogenic protozoan, Neospora, and to live vaccines against neosporosis prepared from the attenuated strains which are useful in the prevention of clinical disease and abortion in mammals.
BACKGROUND OF THE INVENTION
Neospora is a pathogenic protozoan parasite of animals which has recently been recognized as a major cause of abortion, neonatal death, congenital infection, and encephalitic disease in mammals. Dubey and Lindsay, 1993, Parasitology Today, 9:452-458.
N. caninum
infects dogs, and congenitally infects pups, often leading to paralysis. Tachyzoites of
N. caninum
have been isolated from naturally infected pups. Lindsay and Dubey, 1989,
J. Parasitol.
75:163-165. Neospora spp. are a major cause of abortion in dairy cattle. Cases of Neospora related disease, i.e., neosporosis, have also been reported in goats, sheep and horses.
Although
N. caninum
is superficially similar to the pathogen,
Toxoplasma gondii, N. caninum
and
T. gondii
have been distinguished from each other antigenically and ultrastructurally. Dubey and Lindsay, 1993, above. In addition, Neospora-like protozoal parasites isolated from the brains of aborted bovine fetuses and continuously cultured in vitro were shown to be antigenically and ultrastructurally distinct from both
T. gondii
and
Hammondia hammondi,
and most similar to
N. caninum.
Conrad et a/., 1993, Parasitology 106:239-249. Furthermore, analysis of nuclear small subunit ribosomal RNA genes revealed no nucleotide differences between Neospora spp. isolated from cattle and dogs, but showed consistent differences from
T. gondii.
Marsh et al., 1995, J. Parasitol. 81:530-535.
The etiologic role of a bovine isolate of Neospora in bovine abortion and congenital disease has been confirmed. Barr et al., 1994, J. Vet. Diag. Invest. 6:207-215. A rodent model of central nervous system neosporosis has been developed using inbred BALB/c mice infected with
N. caninum.
Lindsay et al., 1995, J. Parasitol. 81:313-315. In addition, models to study transplacental transmission of
N. caninum
in pregnant outbred and inbred mice have been described by Cole et al., 1995, J. Parasitol. 81:730732, and by Long et al., 1996, J. Parasitol. 82:608-611, respectively. Furthermore, an experimental
N. caninum
pygmy goat model that closely resembles naturally acquired Neospora-induced cattle abortion has been demonstrated. Lindsay et al., 1995, Am. J. Vet. Res. 56:1176-1180.
WO 9525541 discloses a biologically pure culture of bovine Neospora, methods of detecting anti-Neospora antibodies and Neospora-specific nucleic acids, and a composition containing a bovine Neospora antigen and carrier for use as a vaccine. WO 9525541 does not, however, teach attenuated live cultures of Neospora, or live vaccines prepared therefrom which are able to trigger a protective immune response in a vaccinated animal.
SUMMARY OF THE INVENTION
In a first aspect, the present invention provides cultures of cells of a strain derived from a pathogenic parent strain of a species of Neospora, which cells exhibit attenuated pathogenicity compared to those of the parent strain but which are capable of triggering an immune response that protects a mammal against neosporosis when administered as a live vaccine.
In a second aspect, the present invention provides vaccines to protect a mammal against neosporosis, comprising an immunologically effective amount of live cells of a strain derived from a pathogenic parent strain of a species of Neospora, which cells exhibit attenuated pathogenicity compared to those of the parent strain but which are capable of triggering an immune response that protects the mammal against neosporosis when administered as a live vaccine, and a veterinarily acceptable carrier. Vaccines of the invention may further comprise one or more other components including, for example, an adjuvant. Vaccines of the present invention may be administered to any mammalian species susceptible to infection and disease caused by Neospora including, but not limited to, dogs, cows, goats, sheep and horses.
In a third aspect, the present invention provides methods for preparing cultures of attenuated cells from a pathogenic strain of Neospora for use in a vaccine that protects a mammal against neosporosis, comprising modifying cells from a pathogenic parent strain of a species of Neospora; selecting and clonally propagating one or more modified cells that exhibit attenuated pathogenicity compared to cells of the parent strain; and selecting and clonally propagating one or more attenuated cells which are capable of triggering an immune response that protects the mammal against neosporosis when administered in a live vaccine.
In a fourth aspect, the present invention provides methods for preparing a vaccine that protects a mammal against neosporosis, comprising modifying cells from a pathogenic parent strain of a species of Neospora; selecting and clonally propagating those modified cells that exhibit attenuated pathogenicity compared to cells of the parent strain but which are capable of triggering an immune response in the mammal that protects against neosporosis when administered in a live vaccine; and combining an immunologically effective amount of the attenuated cells with a veterinarily acceptable carrier in a form suitable for administration as a live vaccine to the mammal.
In a fifth aspect, the present invention provides methods for vaccinating a mammal against neosporosis, comprising administering to the mammal an immunologically effective amount of a vaccine comprising live cells of a strain derived from a pathogenic parent strain of a species of Neospora, which cells exhibit attenuated pathogenicity compared to those of the parent strain but which are capable of triggering an immune response that protects the mammal against neosporosis when administered as a live vaccine, and a veterinarily acceptable carrier.
In a sixth aspect, the present invention provides combination vaccines, comprising an immunologically effective amount of live cells of a strain derived from a pathogenic parent strain of a species of Neospora, which cells exhibit attenuated pathogenicity compared to those of the parent strain but which are capable of triggering an immune response that protects the mammal against neosporosis when administered as a live vaccine; one or more other antigens that trigger an immune response that protects the mammal against a disease or a pathological condition; and a veterinarily acceptable carrier. The combination vaccines may further comprise one or more other components including, for example, an adjuvant.
DETAILED DESCRIPTION OF THE INVENTION
Applicants have discovered that cells of a pathogenic strain of a species of Neospora may be attenuated, and that the resulting attenuated cells are capable of triggering an immune response that protects mammals against neosporosis when administered as a live vaccine. The present invention thus provides cultures of cells of a strain derived from a pathogenic parent strain of a species of Neospora, which cells exhibit attenuated pathogenicity compared to those of the parent strain but which are capable of triggering an immune response that protects a mammal against neosporosis when administered as a live vaccine.
The present invention further provides methods for preparing cultures of attenuated cells of a species of Neospora for use in a vaccine that protects a mammal against neosporosis, comprising modifying cells from a pathogenic parent strain of a species of Neospora, for example, by high serial passage, or by exposure to a mutagenic agent, or by genetic engineering using recombinant DNA techniques; selecting and clonally propagating one or more modified cells that exhibit attenuated pathogenicity compared to cells of the parent strain; and selecting and clonally propagating one or more attenuated cells which are capable of triggering an immune response that protects the mammal against neosporosis when administered in a live vaccine.
As used he
Blagburn Byron L
Brake David A
Lindsay David S
Pfizer Inc.
Portner Ginny Allen
Scully Scott Murphy & Presser
Smith Lynette R. F.
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