Specification
This invention relates to Infectious Bursal Disease Virus antigenic isolates and vaccines FIELD OF THE INVENTION
The present invention relates to novel antigenic isolates of Infectious Bursal Disease Virus, as well as to vaccine compositions containing one or more of these isolates. The invention also relates to new methods for preventing or ameliorating Infectious Bursal Disease in poultry.
BACKGROUND OF THE INVENTION
Infectious Bursal Disease, also called "Gumboro Disease," is an acute and highly contagious viral infection of young chickens and other fowl. It is caused by Infectious Bursal Disease Virus (IBDV) Type I, which is a member of a group of viruses called Birnaviridae. The disease is characterized by degeneration of lymphoid tissue. The primary target of infection is the bursa of Fabricius, although lymphoid damage may also occur in the spleen, thymus, and gland of Harder.
Degeneration of the bursa of Fabricius and other lymphoid tissue in young chickens has severe economic consequences, as the infected chickens have a decreased response to vaccination and an increased susceptibility to other infectious agents such as Newcastle disease, Marek's disease and infectious bronchitis disease. Poultry producers can lose a significant portion of their flock due to IBDV infection. Often times, mortality rates can approach 80% or more in young chickens.
Immunization is the principal method for controlling the disease. Chickens may be passively immunized, by receiving maternally-derived antibodies, or they may be actively immunized with live, live-attenuated, or killed (inactivated) vaccines. Live-attenuated vaccines contain the virus that has been "modified" or attenuated through serial passaging in cell culture. By passaging it is hoped to produce a virus strain that is less pathogenic. In order to be useful in a vaccine, however, it must retain the antigenic and immunogenic properties of the original virus. It must, that is, induce the production of neutralizing antibodies. Control of the disease by immunization had been largely successful until variant strains began to emerge as the result of antigenic drift
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under field conditions. These variants were causing disease in both actively and passively immunized chickens.
Infectious Bursal Disease Virus is often separately classified in the art as either Standard or "STC" strain, or variant types, although the vast majority of wild-type
IBDVs in the United States are now variants. Delaware viruses are some of the most common variant types, and Delaware E in particular has been considered the prototypical variant type for years. IBDV surveys indicate that Delaware E virus is still commonly isolated; however, other variant virus types such as GLS, Rs593 and AL2 have also become quite prevalent. These strains can be characterized using a panel of monoclonal antibodies. In addition, using PCR-RFLP techniques, a distinct molecular class of viruses (called Group 6) have risen in prevalence over the past several years. Amino acid sequencing of this family of viruses shows that most are distinct from the prototype Delaware-E virus in the region generally regarded as perhaps one of the most critical to antigenic identity or uniqueness.
U.S. 5,919,461 relates to a live, variant vaccine strain which is reportedly effective in immunizing young chickens against the Standard, the Delaware and other new-type variant strains.
U.S. 6,471,962 discloses the use of certain monoclonal antibodies in the diagnosis, prevention and treatment of Infectious Bursal Disease.
U.S. 5,192,539 relates to an IBDV vaccine for poultry with antigen material which is derived from a mammalian cell line.
U.S. 5,804,195 provides a vaccine for preventing infectious bursal disease which contains specific strains of live, attenuated but intermediately virulent IBDV. The vaccine may contain other poultry immunogens, including those against Newcastle Disease virus, Marek's disease virus, and infectious bronchitis virus.
In addition, WO 9105569 is related to a diagnostic and vaccine which utilizes an IBDV variant with altered recognition sites.
There currently exists a need in the art for better antigenic isolates of IBDV, as well as vaccines which comprise these isolates for use against IBDV infection. Also needed are better methods of protecting poultry, in particular chickens, from the many variants of the IBD virus, including newer ones that have recently emerged.
SUMMARY OF THE INVENTION
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In one aspect, the invention is directed to a vaccine composition which is effective in preventing or ameliorating Infectious Bursal Disease Virus infection, which comprises an antigen or antigenic component having the substantive identifying characteristics of an Infectious Bursal Disease Virus antigen as set forth in Figure 1 . As that term is used herein, "substantive identifying characteristics" means the amino acid sequence of isolate 28-1 in Figure 1, which comprises only one substitution G -> D at position 318, i.e. 318-D, in major hydrophilic peak B of the Viral Protein-2 (VP-2) of IBDV, and in addition, one or more of the other substitutions noted for isolate 28-1 in Figure 1, including the following: 222-T, 249-K, 254-S or N, 279-N and 286-1. In addition, the antigen or antigenic component should retain substantial reactivity with a basic panel of monoclonal antibodies that characterizes Delaware strain variant viruses.
Thus, the invention provides a vaccine composition comprising an antigen or antigenic component having a 318-D as the only substitution in major hydrophilic peak B of the VP-2 amino acid sequence of Infectious Bursal Disease Virus.
The invention is also directed to a vaccine composition against Infectious Bursal Disease Virus, which comprises the novel 28-1 antigenic isolate of IBDV deposited on March 4, 2004 with the ATCC under Accession Number PTA-5848.
In a further embodiment of the invention there is provided an Infectious Bursal Disease Virus antigenic isolate having a 318-D as the only substitution in major hydrophilic peak B of the VP-2 amino acid sequence which is suitable for use in a vaccine against IBD.
The invention also provides an Infectious Bursal Disease Virus antigenic isolate having the amino acid sequence set forth in Figure 1 (28-1). This is a unique isolate in what is now referred to as the molecular Group 6 family of IBDV isolates.
In addition, there is provided an Infectious Bursal Disease Virus antigenic isolate deposited on March 4, 2004 with the ATCC under Accession Number
PTA-5848 as part of the invention.
Also provided is a method for inducing protection against infection from Infectious Bursal Disease Virus, which involves administering to a poultry animal a vaccine composition containing an antigen having the substantive identifying characteristics of an IBDV antigenic isolate as set forth in Figure 1 .
The invention further provides a method for inducing protection against
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Infectious Bursal Disease, which comprises administering to a poultry animal an antigenic isolate identified with ATCC Accession # PTA-5848.
These and other embodiments, features and advantages of the invention will become apparent from the detailed description and the appended claims set forth herein below.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an amino acid sequence comparison of several reference U.S. variant IBDVs to classic (standard) virus.
DETAILED DESCRIPTION OF THE INVENTION
In one aspect, the present invention is directed to a novel Infectious Bursal Disease Virus (IBDV) antigenic isolate. The isolate is generally characterized as a Delaware-type virus using monoclonal antibody-antigen-capture ELISA, in that it reacts the same as Delaware-E against a limited panel of monoclonal antibodies. In addition, the virus is further characterized using the reverse transcriptase - polymerase chain reaction/restriction fragment length polymorphism (RT-PCR/RFLP) method of Jackwood et al., Restriction Fragment Length Polymorphisms in the VP2 Gene of Infectious Bursal Disease Viruses, Avian Dis. 41:627-637, 1997, as a molecular Group 6 virus (rather than molecular Group 2 to which the prototype Delaware-E variant is assigned).
Referring to Figure 1, further characterization in terms of the amino acid sequence of the variable region of the major antigenic Viral Protein 2 (VP-2) is set forth, along with sequence information from established isolates for comparison. Also included is a summary of the characterization of IBDV isolates with particular attention to the special qualities of the 28-1 isolate as a suitable example (hereinbelow defined). Those skilled in the art will recognize that VP-2 is one of the two major structural proteins of IBDV and is also the target of the serotype-specific neutralizing antibodies which confer protective immunity. (The second major structural protein of the virus, VP-3, does not elicit neutralizing antibodies.)
As Figure 1 illustrates, IBDV isolates have two major and two minor hydrophilic peak regions. Without being bound by theory, all the hydrophilic regions, and in particular the major hydrophilic regions, are believed to have an important effect on antigenicity. The 28-1 isolate has 318-D as its sole substitution in peak B noted in
Figure 1, and is thus separately identifiable from other reference IBDV variants,
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including the classic (standard -STC) strain and the Delaware-E strain. In fact, the 28-1 isolate differs from Delaware-E in what is.generally regarded as the most critical antigenic region of IBDV - major hydrophilic peak B. In addition, the 28-1 isolate of IBDV has one or more of the following additional substitutions: 222-T, 249-K, 254-S or N, 279-N and 286-1 (as per commonly accepted single letter amino acid abbreviations). In addition, the 28-1 isolate differs from the Delaware-A variant at position 222. Delaware-A has 222-Q which is a relatively rare substitution in this position, whereas the 28-1 has 222-T in its preferred embodiment. Most field viruses have 222-T, which perhaps indicates that the 28-1 isolate is a better antigenic match than Delaware-A for U.S. field viruses, and also significant enough to distinguish the two strains as well. A summary of the amino acid patterns in the virus strains presented in Figure 1 is set forth in TABLE 1 below:
Positions 318, 321, 322 and 323 are located in Peak B and amino acid changes result in antigenic change.
Each of the positions above in TABLE 1 has been linked to the binding of neutralizing monoclonal antibodies, and thus the skilled artisan can see the differences between the strains, including the Group 6 28-1 isolate.
Accumulation of data via PCR typing of U.S. field samples has now clearly shown the prevalence and significance of the molecular Group 6 IBDV viruses. Group 6 viruses are by far the most common molecular type recovered from U.S. broilers, accounting for approximately 1 in 3 field isolates, as TABLE 2 below indicates. Without being bound by any theory, the increasing prevalence of Group 6 viruses in U.S. broilers since 1997 is likely a result of more successful escape from Delaware-E and Classic type antibodies provided by conventional IBD vaccines. In support of this concept is the fact that sequencing analysis of several U.S. field samples shows that most IBD viruses in the Group 6 family do not have the Delaware-E substitution pattern in the major hydrophilic Peak B - Jackwood et al., Amino Acid Comparison of Infectious Bursal Disease Viruses Placed in the Same and Different Molecular Groups by RT/PCR-RFLP, Avian Dis. 45:330-339, 2001.
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Table 1. Comparison of reference virus amino acid patterns in critical VP-2 positions.
Virus 222 249 254 286 318 321 322 323
Classic-
STC P Q G T G A G D
Delaware
E T K S I D A G E
GLS T K S T G E G D
Rs593 T K N I G A E D
28-1 r-p K § 1 D A G D
Delaware
A Q K § 1 D A G D
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TABLE 2. Jackwood PCR-RFLP testing system showing the prevalence of
Documents
Application Documents
| # |
Name |
Date |
| 1 |
8539-DELNP-2012-AbandonedLetter.pdf |
2018-08-06 |
| 1 |
8539-delnp-2012-Correspondence Others-(14-12-2012).pdf |
2012-12-14 |
| 2 |
8539-delnp-2012-Assignment-(14-12-2012).pdf |
2012-12-14 |
| 2 |
8539-DELNP-2012-Annexure [28-06-2018(online)]-1.pdf |
2018-06-28 |
| 3 |
8539-delnp-2012-Correspondence-Others-(31-01-2013).pdf |
2013-01-31 |
| 3 |
8539-DELNP-2012-Annexure [28-06-2018(online)].pdf |
2018-06-28 |
| 4 |
8539-delnp-2012-Form-18-(08-03-2013).pdf |
2013-03-08 |
| 4 |
8539-DELNP-2012-FORM 4 [27-06-2018(online)].pdf |
2018-06-27 |
| 5 |
8539-DELNP-2012-FER.pdf |
2017-12-27 |
| 5 |
8539-delnp-2012-Correspondence Others-(08-03-2013).pdf |
2013-03-08 |
| 6 |
8539-delnp-2012-Form-3-(28-03-2013).pdf |
2013-03-28 |
| 6 |
8539-delnp-2012-Claims.pdf |
2014-02-19 |
| 7 |
8539-delnp-2012-Correspondence-others.pdf |
2014-02-19 |
| 7 |
8539-delnp-2012-Correspondence Others-(28-03-2013).pdf |
2013-03-28 |
| 8 |
8539-delnp-2012-GPA-(21-10-2013).pdf |
2013-10-21 |
| 8 |
8539-delnp-2012-Form-1.pdf |
2014-02-19 |
| 9 |
8539-delnp-2012-Form-2.pdf |
2014-02-19 |
| 9 |
8539-delnp-2012-Form-13-(21-10-2013)2.pdf |
2013-10-21 |
| 10 |
8539-delnp-2012-Form-13-(21-10-2013).pdf |
2013-10-21 |
| 10 |
8539-delnp-2012-Form-3.pdf |
2014-02-19 |
| 11 |
8539-delnp-2012-Correspondence-Others-(21-10-2013).pdf |
2013-10-21 |
| 11 |
8539-delnp-2012-Form-5.pdf |
2014-02-19 |
| 12 |
8539-delnp-2012-Assignment-(21-10-2013).pdf |
2013-10-21 |
| 13 |
8539-delnp-2012-Correspondence-Others-(21-10-2013).pdf |
2013-10-21 |
| 13 |
8539-delnp-2012-Form-5.pdf |
2014-02-19 |
| 14 |
8539-delnp-2012-Form-13-(21-10-2013).pdf |
2013-10-21 |
| 14 |
8539-delnp-2012-Form-3.pdf |
2014-02-19 |
| 15 |
8539-delnp-2012-Form-13-(21-10-2013)2.pdf |
2013-10-21 |
| 15 |
8539-delnp-2012-Form-2.pdf |
2014-02-19 |
| 16 |
8539-delnp-2012-Form-1.pdf |
2014-02-19 |
| 16 |
8539-delnp-2012-GPA-(21-10-2013).pdf |
2013-10-21 |
| 17 |
8539-delnp-2012-Correspondence Others-(28-03-2013).pdf |
2013-03-28 |
| 17 |
8539-delnp-2012-Correspondence-others.pdf |
2014-02-19 |
| 18 |
8539-delnp-2012-Claims.pdf |
2014-02-19 |
| 18 |
8539-delnp-2012-Form-3-(28-03-2013).pdf |
2013-03-28 |
| 19 |
8539-delnp-2012-Correspondence Others-(08-03-2013).pdf |
2013-03-08 |
| 19 |
8539-DELNP-2012-FER.pdf |
2017-12-27 |
| 20 |
8539-delnp-2012-Form-18-(08-03-2013).pdf |
2013-03-08 |
| 20 |
8539-DELNP-2012-FORM 4 [27-06-2018(online)].pdf |
2018-06-27 |
| 21 |
8539-delnp-2012-Correspondence-Others-(31-01-2013).pdf |
2013-01-31 |
| 21 |
8539-DELNP-2012-Annexure [28-06-2018(online)].pdf |
2018-06-28 |
| 22 |
8539-delnp-2012-Assignment-(14-12-2012).pdf |
2012-12-14 |
| 22 |
8539-DELNP-2012-Annexure [28-06-2018(online)]-1.pdf |
2018-06-28 |
| 23 |
8539-delnp-2012-Correspondence Others-(14-12-2012).pdf |
2012-12-14 |
| 23 |
8539-DELNP-2012-AbandonedLetter.pdf |
2018-08-06 |
Search Strategy
| 1 |
8539delnp2012search_25-10-2017.pdf |