Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1998-02-12
2001-02-13
Clark, Deborah J. R. (Department: 1633)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C435S320100, C435S235100, C536S023100
Reexamination Certificate
active
06187759
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a DNA vaccine for stimulating protective immunity in animals against a parvovirus. More specifically, the present invention relates to the use of a DNA vaccine for eliciting an immune response against parvovirus in maternally derived antibody (MDA) positive animals. In particular, it relates to the use of a DNA vaccine for eliciting an immune response against canine parvovirus (CPV) in MDA positive dogs. The invention also relates to a plasmid vector suitable for use in a DNA vaccine against parvovirus, in particular canine parvovirus.
BACKGROUND OF THE INVENTION
CPV is primarily an enteric pathogen of CANIDAE. It causes an infection in dogs, especially young dogs, which frequently leads to an enteric disease characterised by acute diarrhoea, fever and leukopenia. It can cause high mortality/high morbidity in infected animals. CPV is genetically and antigenically closely related to Feline panleukopenia virus (FPV), Mink enteritis virus (PEV), Raccoon parvovirus (RPV) and is considered to be a host range variant of one of these viruses.
Vaccines have been developed to prevent parvoviral infection of target animals such as dogs, cats, mink, raccoon, and cattle, in particular dogs and cats. CPV and FPV can be effectively controlled by vaccination with live attenuated CPV and FPV, respectively. Puppies can be protected when maternally derived antibodies are present, by specially developed live attenuated vaccines only, such as described for example in WO 9102054. Such vaccines suffer from the disadvantage that modified live vaccine virus could be excreted post vaccination. The use of an inactivated, adjuvanted preparation, however, may be regarded as safer as no live virus can be excreted post vaccination. Higher concentrations of inactivated vaccine are required to stimulate an antibody response, particularly in the presence of maternally derived antibody (MDA). However, the presence of high titres of MDA can prevent effective vaccination with inactivated vaccines.
In some puppies the passive immunity to certain antigens can persist for a considerable period (4 months or more) at levels sufficient to interfere with vaccination. As the MDA level declines a puppy may be protected insufficiently against infection and disease, but still be refractory to vaccination. Hence, these puppies remain unprotected during a considerable period in their early life. The danger of infection of complete litters poses a serious risk, particularly after the maternally derived immunity has vanished. The potential risk of infection due to the presence of MDA was known for dogs, but has recently been recognized to affect certain neonates of other animals as well, in particular in MDA positive offspring of cats, minks and raccoons.
Recent developments in the vaccine field have resulted in a novel class of vaccines based on the induction of immunity following the delivery of plasmid DNA encoding immunogenic proteins. Such vaccines may hold the promise of protecting against disease by inducing both humoral and cell-mediated immune response, without many of the disadvantages associated with vaccines presently in use.
Whilst it was hoped that the efficacy of DNA immunization would not be reduced by maternally derived antibodies, in practice it has been found that vaccination of one-day-old piglets against pseudorabies, using plasmid DNA incorporating the gD glycoprotein gene of pseudorabies, did not result in significant protection. Piglets from immune sows neither developed an antibody response, nor were primed against pseudorabies virus, as demonstrated by the antibodies kinetics after challenge (see Monteil, M. et al., Vet. Res. (1996), 27, 443-452).
In a recent abstract it has been briefly reported that “immunization of dogs with a range of doses of a plasmid encoding the major capsid proteins of canine parvovirus (VP-1, VP-2) resulted in the dose dependent appearance of anti-parvovirus antibodies at significant levels”. From the subsequent challenge of the dogs, with a mixture of virulent parvovirus strains, it was evident that all immunized dogs were protected against infection and disease. No mention was made in the abstract of the nature of the construct used. Furthermore, there was no reference to the age of the dogs and their immune status.
One of the main limitations of vaccination concerns the vaccination of the young offspring of immune females. In all species the existence of maternal antibodies is a strong limitation which impairs the development of an immune response in the young.
SUMMARY OF THE INVENTION
It has now been found that use of a DNA molecule comprising a vector, preferably a plasmid vector, and at least one isolated nucleotide sequence encoding a parvovirus polypeptide and transcriptional regulatory sequences operably linked to the isolated nucleotide sequence, will successfully immunize puppies earlier in their lives, even in the face of maternally derived antibody. The present invention thus provides for a new and effective method to vaccinate MDA positive animals against parvoviral infections. The DNA molecule according to the invention can be used to facilitate a DNA vaccine to protect for example, dogs from CPV infections, cats from FPV infections and minks from MEV infections.
Further to the unexpected advantage of vaccination of animals in the face of maternally derived antibodies, the present invention provides for a method of vaccination of MDA positive animals that is not restricted by the host range of the corresponding parvovirus. The DNA molecule can be succesfully used in a broad range of MDA positive animals, because it is not limited by cell tropism, as is the case with live virus vaccines. For example, in case the DNA molecule encodes a CPV immunogenic protein, said DNA molecule can be used in vaccination of not only MDA positive dogs, but animals that are host to parvoviruses that are genetically and antigenically closely related to CPV, e.g. FPV, MEV, and RPV, as well.
Maternally derived antibody (MDA) is passively transferred from a seropositive mother to her offspring, who are passively protected during the first few weeks of life by this circulating MDA. It has been calculated that the neonate receives approximately 90% of its MDA via the colostrum, whereas transplacental transfer accounts for only 10% of the total passive antibody. The range of MDA will vary from neonate to neonate, the weaklings or runts often having the lowest MDA levels due to reduced suckling capabilities or opportunities. The “average” neonate soon after birth will have a serum antibody level equal to 50% that of its mother. This MDA proceeds to decline exponentially with a half-life of approximately 10 days.
For example, pups born to bitches with average humoral antibody titers of 1:2560 (HAI) would be expected to contain MDA with titers in the range of 1:1280 during their first week of life. At approximately 7 weeks of age this antibody titer would decline to 1:20-1:40 which is below protective levels but still high enough to prevent most conventional vaccines working. Most puppies (more than 90%) will contain MDA until at least 10 weeks of age. In the field, in contrast to laboratory bred dogs, most dams are immune as a result of previous exposure to field virus or vaccination, therefore puppies of 10 weeks of age or younger born to immune bitches, are considered to be MDA positive. In particular, puppies of 8 weeks of age or younger born to immune mothers are considered as MDA positive dogs that can be protected by the DNA vaccine described herein.
REFERENCES:
patent: 5498413 (1996-03-01), Alvarez et al.
patent: 5593972 (1997-01-01), Weiner et al.
patent: 5882652 (1999-03-01), Valdes et al.
patent: 0117767 (1984-09-01), None
patent: 0341611 (1989-11-01), None
patent: 0554414 (1993-08-01), None
patent: WO 88/02026 (1988-03-01), None
patent: WO 91/02054 (1991-02-01), None
patent: WO 96/14088 (1996-05-01), None
patent: WO 96/12808 (1996-05-01), None
patent: WO 97/40163 (1997-10-01), None
patent: WO 98/03660 (1998-01-01), None
Greenwood Neil
Tarpey Ian
Akzo Nobel N.V.
Clark Deborah J. R.
Sullivan Michael G.
LandOfFree
Canine parvovirus DNA vaccination does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Canine parvovirus DNA vaccination, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Canine parvovirus DNA vaccination will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2609076