In order to gain insight into the pathogenesis of the vesicular lesion of local primary vaccinia infection, newborn rabbits were injected with 0.5 mg of purified inactivated vaccinia virus in an attempt to render them immunologically tolerant. Within a few days these, and control normal rabbits of the same age, were infected on the skin with active vaccinia virus. Most of the tolerant-prepared rabbits failed to develop a local lesion of vaccinia but some developed a very atypical lesion. Successful virus isolation from some, and the presence of inclusions in the tissues of others, indicated successful infection with the virus. Skin allergy to the active virus failed to develop in the test animals but did in the controls. Thus, there was a high degree of correlation between inability to produce delayed hypersensitivity to the viral antigens and failure to develop a vaccinial skin lesion, indicating the probable allergic nature of the primary lesion.

There was also a high mortality rate in the group of tolerant-prepared, infected animals. It was associated with a spreading of the virus from the site of infection to the organs, suggesting that generalized vaccinial infection was the cause of death. The observations were compatible with the hypothesis that death was due to viral toxicity.

The observations also suggest that, in the animal possessing normal immunological function, active immunity develops rapidly, perhaps at the level of the draining lymph node, to prevent appreciable virus from leaving the site of infection.

The absence of detectable immunological activity toward vaccinia virus early in the tolerant-prepared animals and even after 1 month in some of the survivors, indicates that a high degree of immunological tolerance was produced against these microbial antigens.

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