Challenges in developing an oral vaccine for canine parvovirus type 2.

摘要

An oral vaccine to prevent disease caused by canine parvovirus type 2 (CPV-2) would provide certain advantages for vaccinating domestic, wild, exotic and farm raised species susceptible to CPV-2 and antigenically related viruses. Modified live and killed vaccine, with or without oral adjuvants, including plant vectored CPV-2, killed virus with various adjuvant systems, and virus conjugated to an adjuvant, as well as poxvirus vectored CPV-2 were developed or obtained and given orally. Many challenges and failures were encountered, thus it was not possible to develop an oral vaccine for CPV-2.; Transgenic plants expressing the capsid protein, VP1 of CPV-2, were unsuccessful. A novel spontaneous frame-shift mutation caused by the toxicity in E. cola and a new deletion mutation model was proposed. A hot spot specific sequence led to the mutation.; Non-infectious (killed) parvovirus, with and without multiple adjuvants, was used to vaccinate pups orally. Pups were vaccinated orally with 1 to 2 ml of these various mixtures with 2 or more doses given at 2-3 week intervals. None of the orally vaccinated pups developed an immune response to CPV-2 irrespective of the adjuvants nor the number of doses of vaccines.; Multiple doses of MLV CPV-2 vaccines also failed to stimulate a local or systemic antibody response when given orally. In contrast, when these same vaccines were given parenterally (e.g. subcutaneously or IM) all animals developed an antibody. Vaccine virus was more sensitive to inactivation at low pH (pH 3) compared to virulent CPV-2, a possible reason why it failed to immunize when given orally.; A method that appeared certain to immunize dogs orally was a raccoon poxvirus (RCNV) vector that reportedly contained the VP2 construct of feline parvovirus (FPV). However, the FPV construct in RCNV must have been spontaneously expelled as it was not found by either PCR or nested PCR, and VP2 was not found by Western blots.; From the present and previous studies it was concluded that dogs could not be orally immunized with CVP-2 vaccine. We conclude that most methods successfully used to orally immunize animals for certain viruses were unsuccessful with CPV-2.