Licensed Dengue Vaccine: Public Health Conundrum and Scientific Challenge.
Licensed Dengue Vaccine: Public Health Conundrum and Scientific Challenge.
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DOI：
10.4269/ajtmh.16-0222
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发表时间：
2016-10-05
期刊：
影响因子：
--
通讯作者：
Halstead SB
中科院分区：
文献类型：
--
作者：
Halstead SB
赛诺菲巴斯德公司生产的一种由黄热病17D和四种登革热病毒嵌合体（嵌合黄热病登革热[CYD]）组成的四价减毒活疫苗已经完成了在35000多名2-16岁儿童中进行的III期临床试验。该疫苗最近在四个国家获得许可。在前2年的观察中，在10个不同的国家，CYD疫苗的效力在30%到79%之间，总效力为56.8%。在第3年，总体疗效为16.7%，但9岁以下儿童住院的相对风险为1.6,5岁及以下儿童住院的相对风险为4.95。接种血清阴性儿童导致普遍广泛的登革热中和抗体反应，但对突破性登革热病例的保护不力。除非另有证据，否则在接种疫苗的受试者中出现的这种突破性病例应被视为疫苗抗体增强（ADE）。这些病例的来源可以用恢复期血清中的原始抗原免疫反应进行血清学研究。在传统的登革热疫苗疗效临床试验中，接种血清阴性疫苗的人可能因突破性ADE感染而住院，而在安慰剂组中，单型免疫的登革热感染导致住院。疫苗功效试验设计必须通过分别测量血清阴性和血清阳性的功效来确定登革热的病因。CYD疫苗未能提高登革热病毒保护性免疫的原因尚不清楚。为了获得一种安全和具有保护作用的登革热疫苗，在进行四价制剂的实地试验之前，应先对人用单型CYD疫苗进行仔细研究。
A tetravalent live attenuated vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (chimeric yellow fever dengue [CYD]) manufactured by Sanofi Pasteur has completed phase III clinical testing in over 35,000 children 2–16 years of age. The vaccine was recently licensed in four countries. During the first 2 years of observation, CYD vaccine efficacy ranged between 30% and 79% in 10 different countries with an overall efficacy of 56.8%. During year 3, there was an overall efficacy against hospitalization of 16.7%, but a relative risk of hospitalization of 1.6 among children younger than 9 years and 4.95 in children 5 years of age and younger. Vaccination of seronegative children resulted in universal broad dengue neutralizing antibody responses, but poor protection against breakthrough dengue cases. Unless proven otherwise, such breakthrough cases in vaccinated subjects should be regarded as vaccine antibody-enhanced (ADE). The provenance of these cases can be studied serologically using original antigenic sin immune responses in convalescent sera. In conventional dengue vaccine efficacy clinical trials, persons vaccinated as seronegatives may be hospitalized with breakthrough ADE infections, whereas in the placebo group, dengue infection of monotypic immunes results in hospitalization. Vaccine efficacy trial design must identify dengue disease etiology by separately measuring efficacy in seronegatives and seropositives. The reason(s) why CYD vaccine failed to raise protective dengue virus immunity are unknown. To achieve a safe and protective dengue vaccine, careful studies of monotypic CYD vaccines in humans should precede field trials of tetravalent formulations.
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影响因子：
6.4
作者：
Kirkpatrick, Beth D.;Durbin, Anna P.;Whitehead, Steven S.
通讯作者：
Whitehead, Steven S.
影响因子：
9.4
作者：
Chao, Day-Yu;Galula, Jedhan Ucat;Chang, Gwong-Jen J.
通讯作者：
Chang, Gwong-Jen J.
影响因子：
158.5
作者：
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通讯作者：
Saville, M.
DOI：
10.1016/s1201-9712(02)90072-x
发表时间：
2002-06-01
影响因子：
8.4
作者：
Guzman, Maria G.;Kouri, Gustavo;Halstead, Scott B.
通讯作者：
Halstead, Scott B.
DOI：
10.4161/hv.2.2.2555
发表时间：
2006-03-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Guirakhoo, Farshad;Kitchener, Scott;Monath, Thomas P.
通讯作者：
Monath, Thomas P.