A challenge study was performed to measure the protection against CMV afforded by prior natural infection or vaccination with Towne strain live attenuated CMV. Previous studies had shown that seronegative renal transplant recipients were protected by vaccine from serious CMV disease but not from infection. The challenge consisted of a fresh human CMV isolate called Toledo. A closed community of priests volunteered to participate. Twelve seronegative priests were vaccinated with Towne live virus. One year later graded doses of Toledo were administered subcutaneously to the vaccinees and to 6 seronegative and 9 naturally seropositive controls. At a challenge dose of 1000 PFU, even the naturally immune subjects became ill. At a challenge dose of 100 PFU, seronegative individuals developed CMV mononucleosis, whereas both vaccinees and natural immune subjects were protected against illness. However, at this dose half of the vaccinees became infected with the challenge virus. At a challenge dose of 10 PFU of Toledo, vaccinees and natural immunes were protected against infection and disease, while seronegatives became ill with CMV mononucleosis. Neutralizing antibodies and specific cellular immune responses developed after vaccination or disease. This study demonstrates for the first time that active immunization against CMV can prevent disease in normal subjects, even when a challenge is delivered parenterally. However, resistance to CMV depends on the challenge dose and on the integrity of host immune responses.

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Plotkin, S., Starr, S., Friedman, H. et al. COMPARISON OF VACCINE-INDUCED AND NATURAL IMMUNITY TO HUMAN CYTOMEGALOVIRUS (CMV). Pediatr Res 21, 332 (1987).

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