DEVELOPMENT OF VIREMIA AND HUMORAL AND CELLULAR-PARAMETERS OF IMMUNE ACTIVATION AFTER VACCINATION WITH YELLOW-FEVER VIRUS-STRAIN 17D - A MODEL OF HUMAN FLAVIVIRUS INFECTION

To monitor early and late events of immune system activation after pri mary and secondary flavivirus infection, 17 healthy persons were vacci nated with the standard 17D vaccine virus strain of yellow fever (YF). Twelve of these persons had not received YF vaccine previously and 5 had been vaccinated once at least 20 years before. Viremia and various parameters of humoral and cellular immune activation were followed da ily for 7 days and weekly thereafter. Viremia was detected by reverse transcriptase-polymerase chain reaction in all 12 first-time vaccinees beginning from the second to the sixth day after vaccination; most te sted positive between the fourth and sixth day, infectious 17D virus w as detected using a plaque forming assay in the serum of 7 of the 12 f irst-time vaccinees. As first parameters of immune activation, neopter in and beta 2-microglobulin markedly increased between day 2 and day 6 postvaccination. In parallel to the viremia, circulating CD8(+) T-cel ls significantly increased, with peak levels at day 5 after primary va ccination, indicating an activation of the cellular immune system. Nei ther viremia nor significant changes of these activation markers were observed in the five revaccinated persons. Neutralizing antibodies dir ected against the 17D vaccine strain developed in all persons within 2 weeks after vaccination. No correlation was found between the extent of viremia and the titer of neutralizing antibodies. Revaccination was followed by a minor and transient increase of neutralizing antibodies . High titers of neutralizing antibodies persisted for at least 10 yea rs after primary vaccination. J. Med. Virol. 56:159-767, 1998. (C) 199 8 Wiley-Liss, Inc.