A LIVE ATTENUATED DENGUE-1 VACCINE CANDIDATE (45AZ5) PASSAGED IN PRIMARY DOG KIDNEY-CELL CULTURE IS ATTENUATED AND IMMUNOGENIC FOR HUMANS

A dengue-1 candidate vaccine (45AZ5), previously found to be underatte nuated in 2 volunteers, was further attenuated by passage in primary d og kidney (PDK) cell cultures. New candidate vaccines prepared from th ree levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were eac h injected into 9 or 10 volunteers. There was a significant, progressi ve decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees a nd induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for less than or equal to 1 day in 4, and neut ralizing antibody in all 10, which persisted for greater than or equal to 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 45AZ5 for h umans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this stra in are warranted.