EP0198828A1 - Infectious bursal disease virus vaccine - Google Patents
Infectious bursal disease virus vaccineInfo
- Publication number
- EP0198828A1 EP0198828A1 EP85900018A EP85900018A EP0198828A1 EP 0198828 A1 EP0198828 A1 EP 0198828A1 EP 85900018 A EP85900018 A EP 85900018A EP 85900018 A EP85900018 A EP 85900018A EP 0198828 A1 EP0198828 A1 EP 0198828A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- virus
- chickens
- ibd
- polypeptide
- ibd virus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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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
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
- C12N2720/00011—Details
- C12N2720/10011—Birnaviridae
- C12N2720/10022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Definitions
- This invention relates to the identification and characterisation of the major structural protein of infectious bursal disease (IBD) virus of chickens (host-protective immunogen) which stimulates the production of antibody that neutralises the infectivity of IBD virus in vitro and which protects susceptible chickens against infection with virulent IBD virus.
- the invention further relates to the production of an effective sub-unit vaccine against the virus utilising this major host-protective immunogen, as well as to the use of this immunogen in diagnostic tests, assays and the like.
- Infectious bursal disease virus is a pathogen of major economic importance throughout the world poultry industry and is a ubiquitous contaminant of commercial poultry environments.
- the virus causes a highly contagious immunodepressive disease of young chickens, and selectively proliferates in the bursa of Fabricius (one of the two major avian immunological organs) thereby destroying the precursors of the antibody producing plasma cells.
- young chickens day old to 4 weeks
- it directly causes morbidity and mortality, while the capacity to produce antibody responses is inhibited or depressed in chickens which survive infection.
- Such chickens respond poorly to vaccination programs aimed at other avian infections, remain highly susceptible to a variety of bacterial, mycoplasmal and viral pathogens and exhibit very poor weight gain and food conversion ratios.
- the presently used vaccination regimens to control IBDV involve injecting breeder hens (previously exposed to live IBDV) with an inactivated oil-emulsion whole virus vaccine prior to the onset of their period of egg production around 22 weeks of age.
- This inactivated vaccine provokes a major secondary antibody response that is several orders of magnitude (> 100 fold) greater and persists for longer than the responses obtained by repeated vaccination with live virus. This results in the transmission of high levels of protective antibody to each egg throughout the next 40 weeks or so of the egg production cycle. If the antibody levels can be boosted sufficiently it should be possible for broiler chickens, that are slaughtered at 6 weeks of age, to go through their complete rearing period totally protected from IBD virus by maternally derived antibody.
- the presently available inactivated IBD virus vaccine is expensive and difficult to produce since the virus cannot be grown to sufficiently high titres in simple culture systems such as embryonated eggs or tissue culture.
- the viral material required for vaccine production is obtained by infecting six-week-old specified-pathogen-free (SPF) chickens and then harvesting the virus from the infected bursae 3 or 4 days after infection. This procedure for producing an IBD virus vaccine from infected SPF chickens is both laborious and expensive.
- the identification and isolation of the major host-protective immunogen in accordance with the present invention opens the way for development of a safe and inexpensive sub-unit vaccine which is effective in stimulating prolonged high-titre antibody responses in hens to allow the transfer of sufficient maternal antibody to protect young chickens, at least during the critical first few weeks after hatching.
- One object of the work leading to the present invention has been to identify the IBD virus-encoded protein (s) that induce antibody in chickens following natural infection or the injection of a commercial inactivated oil-emulsion whole virus vaccine.
- the 32 Kd polypeptide was a major component of all preparations (as revealed by Coomassie-blue staining of gels) of purified bursal grown Australian IBD virus, with a buoyant density in CsC1 of 1.33 g/ml. The relative amounts of the other polypeptides varied between preparations.
- the 32 Kd polypeptide was estimated to have a molecular weight of approximately 31 Kd when compared with standard molecular weight markers. As a result of further work, however, the molecular weight of approximately 32 Kd is considered to be more accurate.
- the major 32Kd polypeptide of the Australian isolate is comparable in size to the VP-3 protein (MW of 32 to 35 Kd) detected in studies overseas on the Cu-1 isolate of IBD virus grown in vitro or in vivo (Nick et al, 1976; Dobos 1979; Todd & McNulty, 1979; Muller & Becht, 1982).
- the major 37 Kd polypeptide is, however, smaller than the VP-2 (MW of 40 to 41 Kd) of overseas isolates, while the VP-X protein (MW of 47 to 48 Kd - Dobos, 1979; Muller & Becht 1982) was not detected in preparations of the intact Australian virus.
- the 41.5 Kd polypeptide of the Australian isolate is, however, the precursor of the 37 Kd polypeptide, and it is suggested that the 41.5 Kd polypeptide is analogous to VP-X of overseas isolates.
- a non-infectious sub-unit vaccine for use against IBD virus which comprises the structural polypeptide of approximate MW 32 Kd contained in the IBD virus, or an immunogenic peptide derived therefrom, together with, if desired, an adjuvant.
- this invention provides a method of increasing the level of protective antibodies against IBD virus in poultry, particularly breeding hens, which method comprises administering the aforesaid vaccine to said poultry.
- this invention provides a method of providing passive immunity to IBD virus in poultry, which method comprises administering to said poultry an antiserum containing antibodies specific for the 32 Kd structural polypeptide or an immunogenic peptide derived therefrom.
- the 32 Kd polypeptide may be isolated from
- IBD virus for example IBD virus which has been grown in and purified from infected bursae of Fabricius in chickens.
- the vaccine according to this invention may comprise an immunogenic peptide derived from the 32 Kd polypeptide, for example, by "genetic engineering” or chemical synthesis.
- a suitable immunogenic peptide may be derived so that it comprises all or at least the major immunogenic determinants of the 32 Kd polypeptide contained in the IBD virus and thus exhibits the same or similar immunogenicity to the 32 Kd polypeptide.
- the 32 Kd polypeptide may also be coupled to a carrier molecule to increase its immunogenicity and hence its efficacy as a vaccine.
- the non-infectious sub-unit vaccine of this invention comprises an adjuvant.
- the vaccine may, for example, be delivered in an aqueous-mineral oil emulsion, such as an emulsion achieved by using an oil-phase emulsifier (e.g. Arlacel 80) and an aqueous-phase emulsifier (e.g. Tween 80) as described by Stone et al., 1978.
- an oil-phase emulsifier e.g. Arlacel 80
- an aqueous-phase emulsifier e.g. Tween 80
- Additional adjuvants may also be included if required, for example Al OH 3 (Wells et al . , 1979 ) , saponin or a derivative of muramyl dipeptide (Wells at al., 1982).
- methods for assaying both quantitatively and qualitatively the levels of protective antibodies in poultry including breeding hens and their progeny
- methods for assaying the relative concentrations of protective antigen in preparations of IBD virus produced for experimental and commercial inactivated vaccines which methods are characterised by the use as an immunogen of the polypeptide of approximate MW 32 Kd isolated from IBD virus, or an immunogenic peptide derived therefrom. Further details of the methods by which these immunoassays can be carried out are well known in the art, and are accordingly not described in detail here. These methods include the well known ELISA and radioimmunoassays.
- Figure 1 shows the electrophoretic profile of the total RNA isolated from IBD virus which had been fractionated on a 25 to 50% sucrose gradient (10 ml) at 28,000 rpm for 90 min. The white doublets towards the top of the gel in fractions
- Figure 2 shows (a) Polyacrylamide gel electrophoresis of purified IBD virus in a 12.5% gel using the discontinuous SDS-gel system described by Laemmli (1970) .
- the gel was stained with Coomassie brilliant blue to reveal 2 major bands of approximate MW 37 Kd and 32 Kd and 3 others (arrowed) of approximate MW 91.5 Kd, 41.5 Kd and 29 Kd.
- Figure 3 shows the specificity of the serum antibody response of a 6 week-old chicken to live IBD virus, as assessed by reacting 1:500 dilutions of serum collected 3,5,7,10 and 14 days after infection with Western blots of the viral polypeptides separated by SDS-PAGE. 14C-MW markers (Amersham, U.K.) are on the left-hand side.
- Figure 4 shows (a) the specificity of antibodies in serum collected from six 6-week-old chickens, 14 days after they had been infected with IBD virus (tracks 1-6) or in the serum from a chicken that had been infected 28 days previously (track 7).
- Figure 5 shows the specificity of the primary antibody response of 2 SPF chickens (1 and 2) injected at 5 weeks of age with a commercial inactivated oil-emulsion vaccine. Serum obtained from the chickens 4 and 8 weeks (a and b) after primary vaccination are compared with serum obtained 4 weeks (c) after a second injection of inactivated vaccine at 13 weeks of age. Amersham
- Figure 6 shows the specificity of antibodies in sera from a chicken infected at 5 weeks of age with live virus when examined 4 and 20 weeks post- infection (a and b). The chicken was then reimmunised with a commercial inactivated whole-virus vaccine at 25 weeks of age and the specificity of the response examined 4 and 8 weeks later (c) and (d). Amersham 14C-MW markers on left-hand side.
- the isolate 002/73 of IBD virus was originally obtained in Australia by Firth (1974) from commercial poultry with varying degrees of bursitis and identified serologically as IBD virus at the Central Veterinary Laboratory, Weybridge, UK. Following propagation at a limiting dilution of infectivity, the virus was routinely propagated by intraocular inoculation of 4 to 6 week old specified pathogen free (SPF) white leghorn chickens (CSIRO SPF Poultry Unit - Maribyrnong, Victoria, Aust.). Homogenates of infected bursae of Fabricius were prepared as 10% (w/v) suspensions in phosphate buffered saline (PBS) and stored at -80°C. The IBD virus stocks appeared to be free of contamination by other poultry viruses on electromicroscopic examination and did not cross-react in the agar-gel precipitation test with antisera to avian reovirus.
- SPPF pathogen free
- PBS phosphate buffered saline
- the virus was purified by a modification of the method of Todd & McNulty (1979). An equal weight of chilled PBS was added to the freshly harvested bursae which were homogenised in an ice bath by 3 x 20s bursts of a Polytron (PT-10-OD, Kinematica, GMBH, Luzern, Sau) on setting 5. The h ⁇ mogenate was frozen to -80°C and thawed rapidly before an equal volume of the fluorocarbon Arklone (Wertheim Labs . , Melb . Australia) was added and the mixture rehomogenised.
- the aqueous phase (ca 7ml) was prepared in 0.1 M NaCl, 0.01 M Tris-HCl buffer, pH 7.6. After centrifugation at 28,000 rpm for 1.5 h in a Beckmann SW28 rotor at 5°C the gradients were harvested from the bottom in 1 ml fractions.
- the virus was dialysed against NaCl-Tris buffer to remove CsCl and then against NaCl-Tris buffer containing 0.05% (w/v) sodium azide before being stored at 4°C or else made 50% (v/v) in glycerol and stored at -20°C.
- the ELISA method used to assess the presence of IBD viral antigen in various gradient fractions or chicken antibody to IBD virus was essentially that described by York et al., (1983), except that the microtiter trays (Nunc Immunoplate I) were coated with rabbit anti-IBD virus IgG prepared by hyperimmunising rabbits with 002/73.
- To detect viral antigens in the gradient serial dilutions of the fractions were added to the wells, which were then treated with a dilution of chicken anti-serum to IBD virus which produced a maximum OD 450nm of 1.0.
- the viral proteins were transferred to nitrocellulose membrane-filter (Schleicher and Sch ⁇ ll BA83 0.2 ⁇ m) and probed with chicken antisera diluted 1: 500 in 1% (w/v) gelatin in NaCl-Tris buffer.
- chicken antibodies binding to viral polypeptides were identified with rabbit IgG anti-chicken IgG (Cappel Labs, Cochranville, USA) diluted 1:1000 in NaCl-Tris-gelatin buffer followed by I ⁇ Ci of
- Sucrose-gradient fractions were diluted to 1:4 with 10 mM Tris-HCl, 50 mM NaCl, 0.2% SDS buffer, pH 7.05 and treated with 0.5 mg/ml ribonuclease-free Pronase (Worthington, USA) for 1 h at 37°C.
- the solutions were made 0.3 M with respect to NaCl and the nucleic acids extracted with.1 volume of phenol at 56°C for 5 min.
- One volume of chloroform was added to the mixture which was then shaken at room temperature for 10 min before being centrifuged at 12,000 rpm for 2 min in an micro-centrifuge (Eppendorf, W.Germany).
- RNA pellets were washed thoroughly with 67% (v/v) ethanol, dried and then dissolved in 20 ⁇ l water. Samples of RNA were electrophoresed under non-denaturing conditions in 1% (w/v) agarose slab gels in 20 mM phosphate buffer, pH 6.8, together with
- CsCl density-equilibrium centrifugation of complete virus from the continuous sucrose gradients revealed one major band which was visible under reflected light and had a mean buoyant density of 1.33 g/ml.
- a second, less dense, band was frequently seen which appeared by electron microscopy to contain a high proportion of "core" particles.
- purified preparations of intact virus contained 2 major polypeptides with approximate MW of 37 Kd and 32 Kd, and 3 other components (arrows in Fig.2) with approximate MW of 91.5 Kd, 41.5 Kd and 29 Kd.
- polypeptide of MW 32 Kd was a major component of all preparations of virus, densitometer tracings from polyacrylamide gels of different preparations of virus revealed that the relative amounts of the polypeptides varied between preparations.
- Figure 7 shows Western-blots of immune serum collected from three 10-week-old chickens (tracks 1, 2 and 3), 14 days after infection with IBD virus (002/73). Nitrocellulose strips reacted with 25 ⁇ l of serum diluted 1:100. Hyperimmune serum (track 4) included as a positive control.
- Figure 8 shows (a) Protein profile (OD 280nm) of an S200 column fractionation of day 10 immune serum from a 10-week-old chicken infected with IBD virus (002/73).
- Figure 9 shows Western-blots of whole virus with pools of the (a) IgM
- Figure 10 shows Western-blots of sera from adult chickens obtained 3 weeks after immunisation with approximately 50 ⁇ g of purified structural polypeptides of IBD virus (002/73).
- Figure 11 shows Western-blots of 2 anti-32 Kd polypeptide sera (A and B) before (a) and after adsorption with (b) the 37 Kd polypeptide or (c) the 41.5 Kd polypeptide and of 2 anti-37 Kd polypeptide sera (E and F) before (a) and after adsorption with (d) the 32 Kd polypeptide.
- the extraneous antibody activity removed by adsorption is arrowed on each original serum (a) Refer to Table 5.
- Figure 12 shows Western-blots of day 10 immune serum from a chicken infected with 002/73 (L) and day 28 immune serum from a chicken immunised with inactivated vaccine (K) before (a) and after adsorption with the (b) 32 Kd, (c) 37 Kd or (d) 41.5 Kd polypeptides.
- K inactivated vaccine
- IBD virus 002/73
- the virus was routinely passaged by intraocular (i.o.) infection of 4 to 6 week old SPF chickens * Virus infectivity was titrated by inoculating 3-day-old SPF chickens i.o. with 25 ⁇ l of log ln dilutions of a 10% (w/v) homogenate of infected bursae.
- the bursae were harvested from these chickens 72h later , homogenised and IBD viral antigen detected by an enzyme-linked immunosorbent assay (ELISA).
- the titre of virus was expressed as the reciprocal of the dilution of virus that infected 50% of the chickens inoculated (CID 50 ) .
- IBD virus adapted to propagate in chick embryo fibroblast (CEF) culture was initially made available by A.Webster Pty.Ltd., Sydney, Australia. The virus has been designated TC-IBD virus (GT101) and was routinely passaged in CEF cultures. GT101 virus is neutralised in vitro by chicken antisera to type-1 IBD virus, but not type-2 IBD virus (unpublished data - Central Veterinary Laboratory, Weybridge, UK).
- IBD virus (002/73) was grown in bursae then purified as described above. Briefly, a 50% homogenate of the infected bursae in 0.01M Tris-HCl, 0.15M NaCl, pH 7.6 (TBS) was frozen/thawed and homogenised with an equal volume of the fluorocarbon Arklone (Wertheim Labs., Melbourne, Australia). The clarified aqueous phase was centrifuged on stepwise gradients of 40% and 60% (w/v) sucrose. The sucrose interface was collected and centrifuged on preformed 25% to 50% (w/v) CsCl gradients. The purified intact virus banded at a density on CsCl of 1.33g/ml.
- Viral polypeptides were analysed in 12.5% (w/v) polyacrylamide slab gels using the discontinuous SDS gel system of Laemmli (1970), then transferred from the gel onto nitrocellulose paper by the Western blotting technique described by Burnette (1981) and reacted with chicken antibodies as described above. Briefly, the nitrocellulose membrane filter was blocked with a 5% (w/v) solution of dried skim milk powder (blotto) in TBS (Johnson, et al , 1984 ) , cut into 5mm strips then reacted with a 1:100 dilution of chick antisera in blotto, followed by a 1:1000 dilution of rabbit anti-chicken IgG (Cappel Labs.,
- Purified virus was boiled with SDS for 2 min in the absence of reducing agents and the peptides separated by SDS-PAGE.
- the gels were lightly stained with Coomassie-blue, destained and the 29 Kd, 32 Kd, 37 Kd, 41.5 Kd and 91.5 Kd bands of protein cut from the gels.
- the polypeptides were eluted from the gel strips into 0.05M Tris-acetic acid buffer (pH8.0) containing 0.1% (w/v) SDS at 50 volts for 40h.
- the eluted polypeptides were dialysed against multiple changes of distilled H 2 O for 48h and the approximate concentration of the polypeptides assessed by SDS-PAGE against known concentrations of MW markers (Pharmacia, Sweden).
- the purity of the polypeptides was assessed by Western-blotting with hyperimmune chicken serum.
- SPF chickens Six to ten-week-old SPF chickens were inoculated i.o. with infectious virus (002/73) and bled 10 and 14 days later. The serum was collected by centrifugation and stored at -20°C. SPF chickens were also injected intramuscularly (i.m.) with 0.5ml of a commercial inactivated IBD vaccine (Arthur Webster, Pty.Ltd.), and sera collected 28 days later, at the peak of the primary antibody response.
- infectious virus 002/73
- the serum was collected by centrifugation and stored at -20°C.
- SPF chickens were also injected intramuscularly (i.m.) with 0.5ml of a commercial inactivated IBD vaccine (Arthur Webster, Pty.Ltd.), and sera collected 28 days later, at the peak of the primary antibody response.
- IBD vaccine Articlehur Webster, Pty.Ltd.
- Anti-IBD virus antibody in chicken sera and IBD viral antigen in bursal homogenates were both quantitated using the ELISA as described above.
- the virus was allowed to adsorb to monolayers for 60 min at 37°C before each dish was overlayed with 2ml of 0.7% (w/v) agar (Baco-Difco, USA) in HEPES (0.015 M) buffered medium 199 containing 5% (w/v) calf serum.
- HEPES 0.7% buffered medium 199 containing 5% (w/v) calf serum.
- the cultures were incubated at 37°C for a further 6 days and stained by the addition of 0.15% (w/v) neutral red in a 1% agar overlay.
- the end-point of the neutralisation assay was the dilution of serum which caused a 50% reduction in the number of IBD virus plaques.
- Chickens were injected intraperitoneally (i.p.) at 2 days of age with various immune serum or control serum free of antibody to IBD virus.
- the chickens were challenged i.o. with 25 ⁇ l of bursal homogenate, usually containing a minimum of 1000 CID50 of IBD virus 002/73.
- bursal homogenate usually containing a minimum of 1000 CID50 of IBD virus 002/73.
- the chickens were exsanguinated and their bursae removed, weighed and made into a 5% homogenate in saline. Both the levels of antibody in the sera and the presence of viral antigen in the bursae were quantitated by ELISA.
- polypeptides Only the 32 Kd, 37 Kd and 41.5 Kd polypeptides were obtained in sufficient quantity to prepare absorption columns.
- the polypeptides were obtained from unstained gels, guided by Coomassie stained strips taken from each margin of the gel. The purity of the eluted polypeptides was assessed by Western blotting with hyperimmune serum. The polypeptides were quantitated by a Lowry protein assay (Hartree, 1972) and between 150 and 300 ⁇ g of the respective polypeptides were reacted with 1ml of Affigel 10 (Biorad, USA) according to the manufacturers instructions.
- IgM and IgG pools from each serum were injected into groups of four 2-day-old chickens, which were then challenged 1 day later with 10 CID 50 of virus.
- the IgG antibody pools were found to confer protection while chickens injected with the IgM pools of antibody were all susceptible to infection (Table 3).
- Chicken B which produced the strongest response to the 32 Kd polypeptide, also produced antibodies to the 37 Kd and 41.5 Kd polypeptides (Fig.10, track B) and the sera from the 3 chickens (D, E and F) injected with the 37 Kd polypeptide were almost indistinguishable from sera from the 3 chickens (G, H and I) injected with the 41.5 Kd polypeptide (Fig.10, tracks D to I) . It was noted that all of the chickens (D to I) injected with either the 37 Kd or 41.5 Kd polypeptides also produced antibodies that reacted with low MW material on the blots, material that was not recognised by hyperimmune serum from vaccinated chickens (Fig.10, track K).
- Day 10 serum from an infected chicken and day 28 serum from a chicken injected with an inactivated IBD vaccine were also passed through the absorption columns. In neither case did the 37 Kd and 41.5 Kd columns affect the Western-blotting patterns (Fig.12) or the micro-SN titers of the serum (Table 5) . Passing the serum through the 32 Kd column, however, markedly reduced the intensity of the Western-blotting pattern (Fig.12) and reduced the micro-SN titre of the sera by half (Table 5) . In an attempt to improve the efficacy of absorption, day 10 serum was diluted 1:100 prior to being passed through the 32 Kd column. In this case, the plaque-reduction assay (Table 6) showed that the virus neutralising activity in a 1:20,000 dilution of serum was reduced by almost 50%.
- the concentration of antibody in 1 to 2ml of anti-32Kd polypeptide serum was found to be too low to produce detectable levels of circulating antibody when injected i.p. into young chickens.
- An (NH 4 ) 2 SO 4 precipitate of 20ml of anti-32Kd polypeptide serum (Chicken B) was prepared, redissolved in 4ml of PBS, sterile filtered and 1ml injected each of 3 chickens of 2 days of age. These chickens, together with 3 control chickens, were challenged one day later with 10 CID 50 of 002/73, exsanguinated 3 days after challenge and their bursae and serum assessed by the ELISA.
- the 3 chickens that received the precipitated antibody had residual ELISA titres between 160 and 320 and 2 of them had no detectable viral antigen in their bursae.
- the 3 control chickens had no detectable antibody and all had ELISA titres of, viral antigen >128.
- Pasteurella haemolytica vaccines containing different adjuvants Res.Vet.Sci., 27 : 248-250.
- Trypanosoma brucei influence of different adjuvants.
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Abstract
Un vaccin sous unitaire non infectieux destiné à être utilisé contre le virus de maladies bursales infectieuses (IBD) comprend le polypeptide structural d'un poids moléculaire approximatif de 32 kilodaltons contenu dans le virus IBD, ou un peptide immunogène dérivé de celui-ci avec, si on le désire, un adjuvant. Un procédé permettant d'augmenter le niveau des anticorps protecteurs des volailles en administrant le vaccin, ainsi que des procédés de diagnostique sont également décrits.A non-infectious subunit vaccine for use against bursal infectious disease virus (IBD) comprises the structural polypeptide with an approximate molecular weight of 32 kilodaltons contained in the IBD virus, or an immunogenic peptide derived therefrom with, if desired, an adjuvant. A method of increasing the level of protective antibodies in poultry by administering the vaccine, as well as diagnostic methods are also described.
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EP0222842B1 (en) * | 1985-05-30 | 1995-05-10 | Commonwealth Scientific And Industrial Research Organisation | Cloning and expression of host-protective immunogens of ibdv |
US4956452A (en) * | 1987-06-14 | 1990-09-11 | The University Of Maryland | Monoclonal antibody which neutralizes multiple strains of infectious bursal disease virus |
DE3887521T2 (en) * | 1987-06-26 | 1994-08-18 | Commw Scient Ind Res Org | IBDV VP2 EPITOP DETECTED BY VIRUS-NEUTRALIZING AND PROTECTING MONOCONAL ANTIBODIES. |
US5614409A (en) * | 1989-05-30 | 1997-03-25 | Commonwealth Scientific And Industrial Research Organisation | Production of IBDV VP2 in highly immunogenic form |
JPH07206705A (en) | 1993-11-03 | 1995-08-08 | American Cyanamid Co | Live in ovo vaccine |
CN112375125B (en) * | 2020-11-23 | 2021-09-28 | 东北农业大学 | Polypeptide and application thereof in preventing infectious bursal disease of chicken |
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