A Single Dose of Any of Four Different Live Attenuated Tetravalent Dengue Vaccines Is Safe and Immunogenic in Flavivirus-naive Adults: A Randomized, Double-blind Clinical Trial
A Single Dose of Any of Four Different Live Attenuated Tetravalent Dengue Vaccines Is Safe and Immunogenic in Flavivirus-naive Adults: A Randomized, Double-blind Clinical Trial
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DOI：
10.1093/infdis/jis936
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发表时间：
2013-03-15
影响因子：
6.4
通讯作者：
Whitehead, Stephen S.
中科院分区：
文献类型：
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作者：
Durbin, Anna P.;Kirkpatrick, Beth D.;Whitehead, Stephen S.
背景登革热病毒（DENV）每年造成数亿人感染。存在四种登革热血清型，并且先前感染一种血清型增加了第二次异型DENV感染的严重疾病的可能性。在一项随机、安慰剂对照研究中，在113名未接受过黄病毒感染的成人中评价了4种不同的四价登革减毒活疫苗（LATV）混合物的安全性和免疫原性。分别于第0、28、42和180天检测血清中4种登革病毒的中和抗体水平。每种LATV混合物的单次剂量在75%-90%的接种者中诱导三价或更好的中和抗体应答。除皮疹外，疫苗接种者和安慰剂接种者之间的不良事件发生率没有显著差异。三价或更好的反应与皮疹和非黑人种族相关（P <0.0001）。黑人与疫苗病毒血症发生率的降低显著相关。TV 003在90%的黄病毒初治疫苗接种者中诱导了三价或更高的抗体应答，是预防登革热的有希望的候选药物。种族被确定为影响LATV病毒感染性的一个因素，反映了在自然登革热感染中种族对疾病严重程度的影响。
Background. Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue sero-types exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection.Methods. In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults. Serum neutralizing antibody levels to all 4 dengue viruses were measured on days 0, 28, 42, and 180.Results. A single dose of each LATV admixture induced a trivalent or better neutralizing antibody response in 75%-90% of vaccinees. There was no significant difference in the incidence of adverse events between vaccinees and placebo-recipients other than rash. A trivalent or better response correlated with rash and with non-black race (P < .0001). Black race was significantly associated with a reduced incidence of vaccine viremia.Conclusions. TV003 induced a trivalent or greater antibody response in 90% of flavivirus-naive vaccinees and is a promising candidate for the prevention of dengue. Race was identified as a factor influencing the infectivity of the LATV viruses, reflecting observations of the effect of race on disease severity in natural dengue infection.