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Early investigations of the pathogenicity of the adenoviruses (RI-APCARD agents) (1-5) for man revealed (3, 6, 7) that volunteers given tissue culture-grown virus by respiratory, intradermal, or intramuscular routes regularly developed neutralizing and complement-fixing antibodies against the agents without significant illness. This finding led us to attempt to prepare live virus vaccine for human immunization employing types 4 and 7 adenovirus grown in tissue cultures of monkey kidney. When it was found (8, 9), however, that monkey kidney cultures may contain "wild" viruses of unknown pathogenicity for man, the idea of using such untreated monkey kidney material in volunteers was abandoned and a formalin-killed vaccine was prepared instead. The high degree of effectiveness of the killed vaccine in preventing acute respiratory illnesses caused by adenovirus in newly inducted soldiers has been reported elsewhere (10-12). Continued investigation of the live virus vaccine problem was made, employing types 3, 4, and 7 adenovirus produced in tissue cultures of human embryo intestine which had been propagated serially in vitro. Contrary to expectation, volunteers given the trivalent live virus preparation intramuscularly developed acute febrile respiratory illness which resembled closely the natural disease caused by these agents. This report describes the experimental illness induced in the volunteers and presents the antibody responses in these individuals.

Acute Respiratory Illness in Volunteers Following Intramuscular Administration of Live Adenovirus