The immunological role of vaccinia-soluble early antigen was examined in rabbits. The antigens were prepared from HeLa cells infected with a conditional lethal mutant of vaccinia virus, which induces in these cells early antigens including those responsible for surface immunofluorescence of infected cells, but not viral DNA and late protein syntheses. Immunization of rabbits with the antigens in Freund's complete adjuvant induced complement-fixing antibody but neither detectable circulating neutralizing antibody nor any detectable level of inhibitory substance or interferon in the skin of the animals. When immunized animals were inoculated intradermally with vaccinia virus, multiplication of virus in the skin was greatly inhibited, being accompanied by an earlier appearance as well as an accelerated wane of the local reactions. The resistance could not be transferred passively by the serum of immunized animals to normal rabbits. Immunization of rabbits with the antigens without the adjuvant not only failed to inhibit but, contrariwise, enhanced the multiplication of intradermally inoculated vaccinia virus, inducing heavy skin lesions and exalted virus multiplication.

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