@article{e1def099b5a34bf3bb8adaf69c930e16,
title = "rDEN2/4Δ30(ME), a live attenuated chimeric dengue serotype 2 vaccine, is safe and highly immunogenic in healthy dengue-na{\"i}ve adults",
abstract = "rDEN2/4Δ30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4Δ30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4Δ30(ME) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-na{\"i}ve adult volunteers. Eight volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response. The vaccine was well tolerated by all volunteers. The most common adverse events observed were a transient asymptomatic rash and mild neutropenia. All vaccinees seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration. Eleven vaccinees had vaccine virus recovered from the blood during the study. RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the Δ30 mutation in the 3′ UTR. The Δ30 mutation remained unchanged in each isolate, confirming the stability of the Δ30 mutation. Further evaluation of this vaccine in a tetravalent formulation is warranted.",
keywords = "DEN2, Human trial, Live attenuated chimeric dengue vaccine",
author = "Durbin, {Anna P.} and McArthur, {Julie H.} and Marron, {Jennifer A.} and Blaney, {Joseph E.} and Bhavin Thumar and Kimberli Wanionek and Murphy, {Brian R.} and Whitehead, {Stephen S.}",
note = "Funding Information: Dengue viruses (DENV) are positive sense, single-stranded RNA viruses belonging to This research was supported by NIH contract the Flavivirus genus of the Flaviviridae family.1There are four serotypes of dengue virus; N01A115444 and with NIAID funds for DEN1, DEN2, DEN3, and DEN4. Each DENV serotype is capable of causing the full Intramural Research. In addition, Dr. Durbin spectrum of dengue illness ranging from undifferentiated febrile illness to classic dengue received support from the Mid-Atlantic fever (DF) to dengue fever with hemorrhagic manifestations and shock (DHF/DSS).2 Regional Center of Excellence for Biodefense Dengue has become the most important arboviral disease world-wide with an estimated and Emerging Infectious Diseases Research, 50 million infections occurring annually.3,4The activity of dengue continues to increase NIAID UAI057168A, Career Development with more than 100 countries now reporting disease.5 A recent analysis estimated that Award. We would like to thank Priscilla the health burden of dengue in SE Asia is 0.42 DALYs per 1000 population (52% due Brooks, Sabrina Drayton-Weaver, Felipe to premature mortality, 48% due to morbidity) and that the burden could be reduced by Troncoso, Janece Lovchik, and Christopher 82% with an effective vaccine.6 Protective immunity from dengue infection is mediated T. Hanson for their assistance in the recruit-primarily by neutralizing antibody directed against the structural envelope (E) glycoprotein ment and care of volunteers and their expert of the virus.2 Following infection with a particular DENV serotype, life-long immunity to technical {\textcopyright}assi2sta0n0ce6. WLAe NwoDuldE Sal soB lIiOke StoC IEtNhaCt Eserotype is thought to be conferred, although only short-lived heterotypic immunity thank all of the volunteers who participated to other serotypes is generated.7 In addition, epidemiological studies have demonstrated in the trial and whose efforts contribute to the that preexisting immunity to one DENV serotype may confer a greater risk of developing development of a dengue vaccine. more severe disease (DHF/DSS) with subsequent infection by a heterologous DENV.8 For these reasons, it is believed that an effective dengue vaccine must simultaneously induce protective immunity against all four DENV serotypes. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2006",
doi = "10.4161/hv.2.6.3494",
language = "English (US)",
volume = "2",
pages = "255--260",
journal = "Human vaccines",
issn = "1554-8600",
publisher = "Landes Bioscience",
number = "6",
}