Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults
Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults
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DOI：
10.1093/infdis/jiv082
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发表时间：
2015-09-01
影响因子：
6.4
通讯作者：
Whitehead, Steven S.
中科院分区：
文献类型：
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作者：
Kirkpatrick, Beth D.;Durbin, Anna P.;Whitehead, Steven S.
背景。登革热病毒（DENV-1-4）的4种血清型是全球虫媒病毒性疾病的主要病因。理想的登革热疫苗在一次注射后就能对所有血清型提供保护。对168名未感染黄病毒的成人进行了两项随机、安慰剂对照试验，以证明减毒四价登革热活疫苗（TV003）与含有增强DENV-2成分的第二种四价登革热疫苗（TV005）的安全性和免疫原性，并评估6个月时加强剂量的益处。安全性数据、病毒血症和中和抗体滴度进行了评估。单剂TV005在接种3个月后可在90%的疫苗接种者中引起四价反应，在98%的疫苗接种者中引起三价反应。与TV003相比，在TV005试验中，较高剂量的DENV-2组分增加了DENV-2免疫原性的观察频率。第一剂和第二剂的耐受性都很好。在第二次注射后，没有观察到疫苗病毒血症、皮疹或显著的抗体增强。单次皮下注射TV005登革热疫苗是安全的，并在接种者中以前所未有的频率诱发四价抗体反应。第二次注射效果有限，似乎没有必要。确认这些发现和评估疫苗效力的研究现在将转向登革热流行地区的人群。
Background. The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose.Methods. Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated.Results. A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose.Conclusions. A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.