A Live Attenuated Dengue-L Vaccine Candidate (45AZ5) Passaged In Primary Dog Kidney Cell Culture Is Attenuated And Immunogenic For Humans

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Abstract
A dengue-I candidate vaccine (4SAZS), previously found to be underattenuated in 2 volunteers, was further attenuated by passage in primary dog kidney (PDK) cell cultures. New candidate vaccines prepared from three levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were each injected into 9 or 10 volunteers. There was a significant, progressive decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees and induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for ⩽? 1 day in 4, and neutralizing antibody in all 10, which persisted for ⩽5? 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 4SAZ5 for humans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted.

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