Vaccination against canine hookworm (1970)

The work reported in this thesis constituted some of the first steps in the Invention and development of an irradiated vaccine for canine hookworm disease. The thesis is divided into 7 sections of experimental results. There was no significant difference in the infectivities of A. caninum larvae between those given either orally or by subcutaneous inoculation. Exposuije of the infective larvae to various doses of X-rays reduced their infectivity, as measured by subsequent intestinal establishment of adult hookwoms. As the dose of radiation was increased, infectivity was progressively decreased and the pathogenicity of the hookworm burdens were reduced. At X-ray doses of 40 kr and greater, the female worms in the resulting population were invariably sexually sterile. It appeared that larvae irradiated with 40 kr or greater doses of X-rays would be suitable for vaccination experiments. Single vaccination of pups when 3-months-old by subcutaneous inoculation of 1,000 40 kr-irradiated larvae conferred a highly significant resistance when 4-months-old against the establishment and potential morbidity and mortality of a subcutaneous challenge infection with normal larvae. Compared with single vaccination, double vaccination of pups conferred a superior resistance to the establishment of a challenge infection. Double subcutaneous vaccination of 3 and 4-months-old pups with 1,000 40 kr-irradiated larvae was more effective against subcutaneous challenge than was double vaccination by the oral route against an oral challenge. Subcutaneous vaccination conferred equal protection against subcutaneous and oral challenge, while oral vaccination conferred a highly satisfactory protection only against subcutaneous challenge. Complete protection against the potential morbidity of the challenge Infection was exhibited by all double vaccinated pups. The immunogenic efficacies of K-irradiated and of normal A. caninum larvae were compared by double vaccination of 3 and 4-months-old pups. Subcutaneous vaccination with irradiated larvae was wore uniformly effective than were either subcutaneous or oral vaccination with normal larvae. Anthelmintic treatment was a necessary adjunct of vaccination with normal larvae; and this method of vaccination proved to be extremely hazardous for the health and survival of the pups, since S of 14 pups died after vaccination. Subcutaneous vaccination protected pups of different ages and adult dogs against the establishment and potential morbidity of challenge infection. Vaccination was effective when commenced as early as 72 hours after birth of the pups. Adult dogs were also shown to benefit from vaccination, although age per se conferred a considerable additional resistance to primary infection in adult controls. Ago resistance in the vaccinated dogs was additive to their acquired resistance from vaccination. The resistance to both establishment and potential morbidity of challenge infection persisted in the absence of further exposure to hookworm for at least 7 months after completion of the vaccination schedule. Towards the end of the 7 month period age resistance, as exhibited in previously uninfected challenge control pups, augmented the immunity of vaccinated pups against challenge hoofctrorm infection. Vaccinated pups at all ages were completely immune to the pathogenic effects of challenge while older controls were partially (at 8 months) or completely (at 11 months) protected against these effects by age resistance per se. Vaccination with X-irradiated larvae stimulated an apparently maximal immunity which was not further improved by numerous small infection of normal larvae during the period between second vaccination when 4-month-old and challenge infection when 11-months-wold.