WO1988001277A1 - Helminth parasite vaccine - Google Patents
Helminth parasite vaccine Download PDFInfo
- Publication number
- WO1988001277A1 WO1988001277A1 PCT/AU1987/000274 AU8700274W WO8801277A1 WO 1988001277 A1 WO1988001277 A1 WO 1988001277A1 AU 8700274 W AU8700274 W AU 8700274W WO 8801277 A1 WO8801277 A1 WO 8801277A1
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- WIPO (PCT)
- Prior art keywords
- antigen
- synthetic polypeptide
- recombinant dna
- nucleotide sequence
- helminth parasite
- Prior art date
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- 244000000013 helminth Species 0.000 title claims abstract description 23
- 229960005486 vaccine Drugs 0.000 title claims abstract description 18
- 239000000427 antigen Substances 0.000 claims abstract description 30
- 102000036639 antigens Human genes 0.000 claims abstract description 30
- 108091007433 antigens Proteins 0.000 claims abstract description 30
- 241000242711 Fasciola hepatica Species 0.000 claims abstract description 8
- 229920001184 polypeptide Polymers 0.000 claims abstract 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 9
- 241000244154 Taenia ovis Species 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 13
- 108020004414 DNA Proteins 0.000 claims description 11
- 108020004511 Recombinant DNA Proteins 0.000 claims description 11
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- LVSPDZAGCBEQAV-UHFFFAOYSA-N 4-chloronaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC=C(Cl)C2=C1 LVSPDZAGCBEQAV-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
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- 241001672171 Taenia hydatigena Species 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43536—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms
- C07K14/43559—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from trematodes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43536—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms
- C07K14/4355—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from cestodes
- C07K14/43554—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from cestodes from Taenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
Definitions
- the fusion proteins produced by the 5 recombinants listed above contain epitopes of T. ovis oncospheral antigens-. Since oncospheres stimulate resistance to T. ovis in sheep and that resistance to larval cestodes such as T. ovis is antibody- mediated 13-19 and serum from a naturally infected sheep was used for screening purposes, there is a good chance that these fusion proteins contain host protective epitopes of oncospheral antigens.
Abstract
A Helminth parasite vaccine comprising a synthetic polypeptide displaying the antigenicity of all or a portion of an antigen of a helminth parasite such as Tacnia ouis or Fasciola hepatica.
Description
"HELMINTH PARASITE VACCINE"
This invention concerns new vaccines against helminth parasites, developed using recombinant DNA technology, and use of these vaccines as agents to stimulate the immune response against such parasites in animals and man.
The devastating effects of helminth and other parasitic diseases on human health and economic developmen 'in emerging nations, and on agricultural production in industrialised societies, are well known. However, progress in parasitological research to limit these effects in an ecologically desirable way - by vaccination rather than by the use of drugs - has been extremely slow. With few exceptions, helminth parasites, unlike bacteria and viruses, cannot be grown satisfactorily in vitro. Hence, the availability of parasite antigens, for biochemical and immunological studies as well as for investigations of their potential as vaccines, is limited.
Crude preparations of parasites have been widely used in attempts to stimulate immunity to reinfection, but with generally poor results. -The very complexity of these preparations militates against their use as vaccines; they may contain at least 60 different antigens. Moreover, the purification of a single species of antigen from such
complex mixtures represents a formidable task. Slightly more encouraging results have been obtained with excretory/secretory antigens of parasites, but unfortunately supplies of these antigens are extremely scarce ' .
Because of the difficulties referred to above, new antigenic materials and a method for obtaining them are required before vaccination against helminth parasites is practicable. It is an object of the present invention to overcome the foregoing problems.
In its broadest aspect, the invention concerns the application of recombinant DNA technology to the preparation of helminth antigens in sufficient purity and quantity for vaccination purposes.
According to a first aspect of the present invention, there is provided a recombinant DNA molecule which comprises at least one nucleotide *• sequence which codes for all or a portion of a helminth parasite antigen. In this aspect, the invention also provides a method for the production of such a recombinant DNA molecule.
In a further aspect, the invention provides a recombinant DNA cloning vehicle or vector containing a recombinant DNA molecule as described above, and a method for the production thereof. The invention further provides a host cell containing such a cloning vehicle or vector. The host cells may, for example, be micro-organisms or tissue culture cells. In yet another aspect, this invention provides antigenic products expressed by host cells containing recombinant helminth parasite DNA sequences as described above.
In a further aspect, the invention encompasses vaccine compositions based on the use of expressed products from recombinant helminth parasite DNA as antigens , individually or in combinations , for
5 inducing an immune response in animals and/or humans against helminth parasite antigens.
The present invention also extends to antibodies produced by a host in response to administration of an antigenic product as described
]_Q above. Such antibodies may, for example, be used in immunodiagnostic agents, test kits and the like.
The invention described herein is applicable generally to the preparation of helminth parasite vaccines based on recombinant antigenic products of τ_5 helminth parasite DNAs expressed in micro-organisms or tissue culture cells. It is illustrated particularly by the expression in bacteria of genes coding for helminth antigens which can stimulate immunity to re-infection - the so-called host protective 3 20 antigens . Such antigens are a necessary ingredient in. any vaccine. The production of such antigens corresponding to the liver fluke (Fasciola hepatica) , a livestock 4 and human pathogen5 , and larval taeniid cestodes (Taenia hydatigena, Taenia ovis, Echinococcus 5 granulosus) which are of the particular economic importance to the production of sheep, exemplify the process 6,'7.
Further features of the present invention will be apparent from the following Example which 0 illustrates, by way of example, the method of production of recombinant helminth parasite DNA and the expression of antigenic products by host cells containing parasite DNA.
5
EXAMPLE
A. Cloning and Expression of Helminth Parasite DNA Messenger RNA from adult tapeworms (Taenia ovis) and liver flukes (Fasciola hepatica) was isolated and the poly-A + fraction purified8. The poly-A RNA was then used as a template for the in vitro synthesis of CDNAY9H. The cDNA was then cut with the restriction enzyme Sau 3 to an average length of 300-500 base pairs and inserted into the Bam HI site of the plasmid vectors pEX 1, pEX 2 and pEX 3 " The vector is phosphatased prior to ligation with the Sau 3A-cut cDNA and the recombinant plasmids used to transform Escherichia coli MC 1061 which contains another plasmid bearing a temperature sensitive repressor. Transformed bacteria are grown at 30°C on Luria agar containing ampicillin and replicated onto nitrocellulose filters. Protein synthesis is initiated by transferring the filter to 42°C. Those bacteria producing parasite antigens are detected using serum from sheep experimentally infected with the parasites in question which contains antibodies to those antigens. The detection technique involves lysing the recombinant colonies with sodium dodecyl sulphate, and renaturing the proteins by electrophoresis in a Western blot apparatus . The nitrocellulose filters are then treated with serum from infected sheep-containing antibodies to the parasite antigens, washed thoroughly to remove unbound material, then treated with rabbit anti-sheep immunoglobulin coupled with horse-radish peroxidase, washed again to remove unbound material, then treated with horse-radish peroxidase colour development reagent (4-chloro-l-naphthol) . The positive clones
stain a dark blue colour. Background staining is eliminated by absorbing the sheep serum with lysed colonies of the parental bacterial host prior to its use for reacting with the recombinant colonies containing parasite DNA. Positive clones identified in this way as producing parasite antigens have been designated pTO 1, 2, .... 10 and pFH 1, 2 , . . . . 6.
The helminth DNA products expressed by these bacteria are unique and they may be used alone or in combination, to vaccinate sheep against liver fluke and larval tapeworm infection. Since the positive clones were orginally isolated from a cDNA library screened with serum from sheep infected with the parasite in question, the DNA which they contain is clearly expressed as an antigenic material by intact parasites during the course of a normal infection.
B. Polyacrylamide Gel Electrophoresis* (PACE) and Western (WB) of Hybrid Proteins i) Methods
Hybrid proteins expressed by the pEX recombinants containing T. ovis cDNA inserts were analysed in a BioRad Protean Cell by PAGE, in 8% gels containing SDS.12], as well as by WB[11]. A loopful of bacteria from glycerol stocks was used to inoculate 10 ml L-broth containing ampicillin at lOOμg/ml. The culture was maintained with shaking at 30°C until the optical density (680 nm) reached about 0.15. The culture was then transferred to 42°C for 2 h to induce synthesis of hybrid proteins.
2.5 ml of the culture was centrifuged for 2' on an Eppendorf centrifuge. The pellet was resuspended in 0.5 ml M Tris pH 7.3 containing 1 mg/ml lysozyme and 0.1% Triton X-100 and left to stand for
30 min at room temperature. After centrifugation as above the supernatant was discarded. 60μl of 2 x SDS sample buffer and 60μl water were added to each pellet along with 5μl α-mercaptoethanol, then vortexed, boiled for 2 min and centrifuged again. 30μl samples were loaded onto gels which were run at 40 ma for 3-4 h. Molecular weight markers were included on each gel along with samples from bacteria infected with one of the parent plasmids (pEXl) and a recombinant that was negative in the antibody screening procedure.
When Western blots were performed, gels were set up in a transblot apparatus (BioRad) and the proteins transferred to nitrocellulose overnight. The nitrocellulose was then probed with Ewe 5 (a sheep which had experienced a natural infection of T. ovis) serum or normal serum. In addition, Western blots ' were alsoιprobed with an antiserum to sonicated oncospheres prepared in Balb/c.mice. These mice received 100μg of sonicated T. ovis oncospheres in Freund's complete adjuvant i/m into the thighs on 3 occasions, 2 weeks apart, prior to bleeding out and preparing serum. This serum had a titre of about 1/10000 in a dot blot assay using 2μg samples of T. ovis oncospheral antigens; the second antibody was goat anti-mouse Ig coupled to horseradish peroxidase (HRP)
ii) Nature of the Expressed Hybrid Proteins
Induced bacterial extracts were examined by SDS-PAGE. The cro-lac fusion protein expressed by the parental vectors (pEXl, 2 and 3) has a molecular weight of 117 kDa. Three of the recombinants (referred to as TOl, T03 and T05) expressed hybrid proteins of around 165 to 170 kDa of which the T. ovis
component was between 48 and 55 kDa. Two (T07 and T08) expressed hybrid proteins only slightly larger (by 0.5 - 1.5 kDa) than the parental type.
When replicas of SDS-PAGE gels of recombinant bacterial extracts v/ere transferred to nitrocellulose by Western blotting and screened with Ewe 5 serum, only bands corresponding to the expressed' hybrid proteins of TOl, T03, T05, T07 and T08 were detected. The parental cro-lac protein and that of a negative recombinant did not react in the test. A similar replica probed with mouse anti-T. ovis oncosphere serum (at a 1:10 dilution) and goat anti-mouse Ig coupled with HRP (at 1:1500) stained the hybrid protein bands of the 5 recombinants which had reacted positively with Ewe 5 serum. Negative results were obtained with appropriate normal sera.
>
;Lii) Conclusions
The fusion proteins produced by the 5 recombinants listed above contain epitopes of T. ovis oncospheral antigens-. Since oncospheres stimulate resistance to T. ovis in sheep and that resistance to larval cestodes such as T. ovis is antibody- mediated 13-19 and serum from a naturally infected sheep was used for screening purposes, there is a good chance that these fusion proteins contain host protective epitopes of oncospheral antigens.
C. Vaccination of Sheep with Recombinant Fusion Proteins of T. ovis i) Methods
Large scale cultures of recombinants TOl,
T03, T05, T07 and T08 were prepared, and each of the fusion proteins was purified using a 8 M urea
extraction procedure followed by separation over Sephacryl S-200 and dialysis against low ionic strength buffer (phosphate buffered saline or PBS) to remove urea. A "cocktail" vaccine consisting of 1 mg of each fusion protein in 0.5 ml of PBS was mixed with an equal volume of adjuvant (Ribi adjuvant system) and injected intramuscularly in the left rear leg of 12 months old Dorset x Merino and Border Leicester x Meriono sheep (a total of 7) . Two control groups were included: 7 sheep that had no treatment and a further 7 sheep that had PBS injections alone. Booster injections of the fusion protein "cocktail" plus adjuvant were given 3 weeks later, and two further boosters of fusion protein "cocktail" alone at 3 week intervals subsequently. The sheep were challenged with 5000 Taenia .ovis eggs 1 week after the last injection and necropsied 10 weeks later. The sheep were bled regularly from before the start of vaccination until the time of necropsy 10 weeks after challenge.
ii) Results
By comparison with the control groups, the vaccinated sheep responded to the vaccination procedure and produced antibodies to T. ovis oncospheral antigens (as measured by a dot-blot test) . However, the results were somewhat variable and the titres were not always high (<1:40) . The vaccinated sheep responded strongly to the β-galactosidase component of the fusion protein (>1:640) .
iii) Conclusion
The vaccinated sheep produced detectable levels of antibody to antigenic determinants of T. ovis oncospheres. This shows that the T. ovis component of the fusion protein was seen by the sheep, who responded by producing antibodies.
D. Nucleotide Sequences of Recombinants TOl, 3, 5, 7 and 8 Three pEX plasmids containing T. Ovis DNA inserts have been at least partially characterised for their DNA sequences. In all clones both strands have been sequenced and the data analysed using the Staden
24 25 programs ' and Staden' s ANALYSED programs. The T. ovis inserts were excised from pEX vectors using restriction endonuclease sites present in the pUC18 polylinker in the plasmid and sites present within th "β-galactosidase gene. The inserts were mobilised to pUC18 -and PUC19 plasmid vectors, from which DNA fragments containing the T. ovis DNA were isolated. These fragments were subσloned into the viruses Ml3 mpl8 and mpl9 for sequencing by the dideoxy chain termination procedure 20-23
The clones have been named pTOl , pT03 , pT05 , ρT07 a d pT08 for identification purposes. Clones pT07 and pT08 contain small inserts and have been fully sequenced.
The pT07 insert consists of 87 nucleotides. The sequence of pT07 is presented in Fig. 1. This DNA fragment has two possible reading frames (clone 7a and clone 7b) and the deduced amino acid sequence for each is also presented in Fig. 1.
The pTo8 insert consists of 93 nucleotides. The nucleotide sequence and the deduced amino acid
sequence of an open reading frame are presented in Fig. 2.
The pT03 insert is 1100 nucleotides long, of which 697 bp have been sequenced from the 5 * end (clone 3a) and 357 bp from the 3' end of the insert
(clone 3b) . The sequencing of this fragment is being carried out using the shotgun method of sequencing 24
The region between the ends of the clone of approximately 50-100 bp is still to be sequenced. The nucleotide sequence and the deduced aminoacid sequence of these fragments are presented in Fig. 3.
It will be understood that the inventive concept is not limited by application to the expression in bacteria of helminth antigens as vaccines for sheep but that the concept may be realised using other recombinant organisms or cells and the antigenic vaccines may find application in humans and a Vide range of animal species 26. . "
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2. Lloyd (1981). Parasitology, 83_, 225.
3. Mitchell (1979). Adv. Immunol. 2 _, '451.
4. Malek (1980). Snail-transmitted Parasitic Diseases. Vols. 1 and 2, CRC Press, USA.
5. Boray (1982). In: Biology and Control of Endoparasites (eds. L.Symons, A.Donald and J.Dineen) Academic Press, Sydney.
6. Arundel (1972). Aust.Ve.J. 48, 140.
7. Howkins (1975). Sci. Tech. 13, 11.
8. Irving, and Howell (1981) Mol.Biochem. Parasitol. , 337.
9. Guber, and Hoffman (1983) Gene 25, 263.
10. Stanley and Luzio, (1984). The EMBQ Journal 3, 1429.
11. Burnette, W.M. (1981) Anal. Biochem. 112, 195-203.
12. Laemmli, U.K. (1970) Nature 227, 680-685.
13. Rickard, M.D. and Williams, J.F. (1982) Adv. Parasitol. 21, 241-296.
14. Rajasekariah, G.R., Rickard, M.D., Mitchell, G.F. and Anders, R.F. (1982) Int. J. Parasitol. 12, 111-116.
15. Lightowlers, M.W. , Mitchell, G.F. , Bowtell, D.D.L., Anders, R.F. and Rickard, M.D. (1984) Int.J. Parasitol. 14, 321-333.
16. Lightowlers, M.W. , Rickard, M.D. and Mitchell, G.F. (1986a) Int. J. Parasitol. 16, 297-306.
17. Lightowlers, M.W. , Rickard, M.D. and Mitchell, G.F. (1986b) Int. J. Parasitol. 16, 307-315.
18. Urquhart, G.M. (1980) Symp. Brit. Soc. Parasitol. 18_, 107-114.
• »
19. Bowtell, D:D.L., Saint, R.B., Rickard, M.D. and Mitchell, G.F. (1984) Mol. Biochem. Parasitol, 13, 173-185.
20. Sanger, F., Nicklen, S. and Coulson, A.R. (1977) Proc. Natl. Acad. Sci. USA 74, 5463-6457
21. Sanger, F. and Coulson A.R. (1978) FEBS Letters 8 , 107-110.
22. Schreier, P.H. and Cortese, R.J. (1979) J. Mol. Biol. 129, 169-172.
23. Yanish-Perron, C, Vierira, J. and Messng, J.
(1985) Gene 33, 103-119.
24. Staden, R. (1979) Nucleic Acid Res. 6, 2601-2610
25. Staden, R. (1982). Nucleic Acid Res. 10, 4731-4751.
26. Urquhart (1980). In: Vaccines Against Parasites (eds. A.Taylor and R.Muller) Blackwell, Oxford.
Claims
1. A recombinant DNA molecule comprising at least one nucleotide sequence which codes for all or a portion of a helminth parasite antigen.
2. A recombinant DNA molecule according to claim 1, wherein said nucleotide sequence codes for all or a portion of an antigen of Taenia ovis.
3. A recombinant DNA molecule according to claim 2, wherein said nucleotide sequence comprises or includes a base sequence substantially as shown in any one of Figures 1, 2 or 3.
4. A recombinant DNA molecule according to cla_im 1, wherein said nucleotide sequence codes for all or a portion of an antigen of Fasciola hepatica.
5. A recombinant DNA cloning vehicle or vector having inserted therein a nucleotide sequence according to any one of claims 1 to 4, said sequence being operatively linked to an expression control sequence.
6. A host cell transformed with a cloning vehicle or vector according to claim 5.
7. A synthetic polypeptide displaying the antigencity of all or a portion of a helminth parasite antigen.
8. A synthetic polypeptide according to claim 7, which displays the antigencity of all or a portion of an antigen of Taenia ovis.
9. A synthetic polypeptide according to claim 8, which comprises or includes an amino acid sequence subtantially as shown in any one of Figures 1, 2 or 3.
10. A synthetic polypeptide according to claim 7, which displays the antigencity of all or a portion of an antigen of Fasciola hepatica.
11. A synthetic polypeptide according to claim 7, which further comprises an additional polypeptide coded for by the DNA of a host cell or cloning vehicle or vector fused thereto.
12. A vaccine composition for inducing an immune response against a helminth parasite antigen, which comprises at least one synthetic polypeptide according to any one of claims 7 to 11, together with a pharmaceutically or veterinarilly acceptable carrier or diluent therefor.
13. A vaccine composition according to claim 12, further comprising an adjuvant.
14. A method of inducing an immune response against a helminth parasite antigen, which comprises administration of a vaccine composition according to claim 12 or claim 13.
15. Antibodies produced by a host in response to the administration to the host of at least one synthetic polypeptide according to any one of claims 7 to 11, or a vaccine composition according to claim 12 or claim 13.
16. An immunodiagnostic agent comprising an antibody according to claim 15.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU750886 | 1986-08-18 | ||
| AUPH7508 | 1986-08-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1988001277A1 true WO1988001277A1 (en) | 1988-02-25 |
Family
ID=3698198
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/AU1987/000274 WO1988001277A1 (en) | 1986-08-18 | 1987-08-18 | Helminth parasite vaccine |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1988001277A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2219590A (en) * | 1988-05-12 | 1989-12-13 | Nz Ministry Agriculture & Fisheries | Antigenic polypeptides of taena ovis |
| GB2232675A (en) * | 1989-05-09 | 1990-12-19 | Pitman Moore New Zealand Limit | Stable forms of antigenic taenia ovis polypeptides |
| WO1992003735A1 (en) * | 1990-08-20 | 1992-03-05 | British Technology Group Ltd | Liver fluke diagnostic system |
| US5348740A (en) * | 1988-05-12 | 1994-09-20 | Coopers Animal Health Nz Ltd. | Antigenic polypeptides of Taenia ovis |
| WO1994028925A1 (en) * | 1993-06-15 | 1994-12-22 | Mallinckrodt Veterinary Inc. | Vaccine containing a serine protease |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3609584A (en) * | 1983-12-01 | 1985-06-06 | Washington University | Circulating antigens of dirofilaria immitis,monoclonal antibodies specific therefor and methods of preparing such antibodies and detecting such antigens |
| US4568639A (en) * | 1982-07-19 | 1986-02-04 | Lew Kenneth K | Method for the commercial production of helminths antigens |
| AU3497484A (en) * | 1984-01-10 | 1986-05-08 | Lew, K.K. | Method for the commercial production of helminths antigens |
| AU5310286A (en) * | 1984-12-21 | 1986-07-22 | National Research Development Corp. | Liver fluke antigens |
-
1987
- 1987-08-18 WO PCT/AU1987/000274 patent/WO1988001277A1/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4568639A (en) * | 1982-07-19 | 1986-02-04 | Lew Kenneth K | Method for the commercial production of helminths antigens |
| AU3609584A (en) * | 1983-12-01 | 1985-06-06 | Washington University | Circulating antigens of dirofilaria immitis,monoclonal antibodies specific therefor and methods of preparing such antibodies and detecting such antigens |
| AU3497484A (en) * | 1984-01-10 | 1986-05-08 | Lew, K.K. | Method for the commercial production of helminths antigens |
| AU5310286A (en) * | 1984-12-21 | 1986-07-22 | National Research Development Corp. | Liver fluke antigens |
Non-Patent Citations (6)
| Title |
|---|
| BEARDSELL, P.L. and M.J. HOWELL, Parasitology Today, Volume 3, No. 1, published 1987, (Elsevier Science Publishers B.V., Amsterdam), "Production of Parasite Antigens by Co-transformation", see pages 28 to 29. * |
| BOWTELL, D.D.L. et al., Molecular and Biochemical Parasitology, Volume 13, published 1984, (Elsevier Science Publishers B.V., Amsterdam), "Expression of Taenia taeniaeformis Antigens in Escherichia Coli", see pages 173 to 185. * |
| BOWTELL, D.D.L. et al., Parasitology, Volume 93, published 1986, (Cambridge University Press, Cambridge), "Immunochemical Analysis of Taenia Taeniaeformis Antigens Expressed in Escherichia Coli", see pages 599 to 610. * |
| GAMBLE, H.R. and D.S. ZARLENGA, Veterinary Parasitology, Volume 20, published 1986, (Elsevier Science Publishers B.V., Amsterdam), "Biotechnology in the Development of Vaccines for Animal Parasites", see pages 237 to 250. * |
| HILLYER, G.V. and A.E. SERANO, American Journal of Tropical Medicine and Hygiene, Volume 32, No. 2, published 1983, (Allen Press, Lawrence, USA), "The Antigens of Paragonimus westermani, Schistosoma mansoni, and Fasciola hepatica Adult Worms", see pages 350 to 358. * |
| SANTIAGO DE WEIL, N. et al., International Journal of Parasitology, Volume 14, No. 2, published 1984, (Pergamon Press Ltd, Oxford), "Isolation of Fasciola hepatica Genus-Specific Antigens", see pages 197 to 206. * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2219590A (en) * | 1988-05-12 | 1989-12-13 | Nz Ministry Agriculture & Fisheries | Antigenic polypeptides of taena ovis |
| GB2219590B (en) * | 1988-05-12 | 1992-09-30 | Nz Ministry Agriculture & Fisheries | Antigenic polypeptides of taena ovis |
| US5348740A (en) * | 1988-05-12 | 1994-09-20 | Coopers Animal Health Nz Ltd. | Antigenic polypeptides of Taenia ovis |
| US5599692A (en) * | 1988-05-12 | 1997-02-04 | Coopers Animal Health Nz Limited | Antigenic polypeptides of Taenia ovis |
| US5618542A (en) * | 1988-05-12 | 1997-04-08 | Coopers Animal Health Nz Limited | Vaccines comprising antigenic polypeptides of Taenia ovis |
| GB2232675A (en) * | 1989-05-09 | 1990-12-19 | Pitman Moore New Zealand Limit | Stable forms of antigenic taenia ovis polypeptides |
| GB2232675B (en) * | 1989-05-09 | 1993-05-12 | Pitman Moore New Zealand Limit | Stable forms of antigenic taenia ovis polypeptides |
| WO1992003735A1 (en) * | 1990-08-20 | 1992-03-05 | British Technology Group Ltd | Liver fluke diagnostic system |
| WO1994028925A1 (en) * | 1993-06-15 | 1994-12-22 | Mallinckrodt Veterinary Inc. | Vaccine containing a serine protease |
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