Canine parvovirus (CPV) is primarily an enteric pathogen that infects dogs, especially young dogs. Parvovirus infection is characterized by acute diarrhea, fever and leukopenia in dogs and puppies more than 4 to 5 weeks old, and in rare cases myocardial disease in younger puppies. The mortality rate from the disease in unvaccinated dogs is very high. And while several CPV vaccines exist, the presence of maternally-derived antibodies (MDA) tends to block the ability of otherwise effective vaccines to provide protective immunity.
Newborn puppies acquire passive immunities against diseases such as CPV infection by nursing from their mother, especially during the first two days of life. A puppy that nurses takes in colostrum in the milk that is first produced and (MDA) in the colostrum are passed to the puppy. For dogs—and many other mammals—the level of passive immunity provided by the colostrum gradually decreases as MDA are catabolized. As such, the age at which a puppy is no longer protected by MDA varies widely, depending upon the puppy's intake of colostrum, the amount of antibodies contained therein, and several other factors.
A particular challenge when vaccinating puppies is to administer vaccines according to a time frame that provides protection which overlaps the protection provided by maternal antibodies and begins as maternal antibodies wane. Currently, vaccine regimens for puppies typically begin at about 6 weeks of age and boosters are given about every 3 weeks thereafter, e.g. at 9, 12 and sometimes 15 weeks. However, in order for this regimen to provide full protection, the first vaccine dose would have to immediately elicit a protective immune response. This expectation is entirely unrealistic due, in part, to the immaturity of the puppy's immune system and the time period required to mount an immune response. Moreover, the situation is further complicated because residual MDA, which may persist up to about six weeks of age, neutralize MLV vaccines. Currently, all commercially available CPV vaccines are MLV vaccines.
Importantly, while a puppy with CPV MDA may not respond to any MLV CPV vaccine, it can still be infected by a virulent field strain of CPV, and develop canine parvovirosis. Because of the MDA interference, full protection usually does not develop until the entire course of vaccinations is given. As a consequence, the age-based mortality due to CPV infection peaks prior to completion of vaccination protocols. Accordingly, developing a vaccine that actively immunizes puppies after the first injection—and in the presence of MDA—is one of the most important unmet needs in canine medicine.
Another challenge in veterinary medicine is the treatment of cancer, e.g., in dogs. There are many limitations in the existing tools for cancer therapy, especially for geriatric dogs. The administration of oncolytic parvoviruses to kill cancer cells shows great promise as an effective cancer treatment (Rommelaere et al, Cytokine & Growth Factor Reviews 21:185-195, 2010; and U.S. Pat. No. 7,179,456 to Rommelaere et al, the complete contents of which are herein incorporated by reference) and might be applied to canines. However, the existence of pre-existing antibodies to parvoviruses (e.g. as a result of vaccination) would render this method ineffective, since the parvovirus would be neutralized by the existing antibodies. In addition, gene therapy in dogs is rarely undertaken at present but would be a promising method for treating several disorders, if suitable nucleic acid vectors are identified. Accordingly, methods to overcome existing antibodies would be useful for applications beyond vaccination.
In light of the above, there is a need for vaccines with an improved safety and a good efficacy, including the ability to overcome MDA including vaccines that provide protection against heterologous CPV strains.