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描绘针对减毒活四价登革热疫苗的血清型特异性中和抗体应答。

Delineating the serotype-specific neutralizing antibody response to a live attenuated tetravalent dengue vaccine.

机构信息

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.

出版信息

Vaccine. 2018 Apr 25;36(18):2403-2410. doi: 10.1016/j.vaccine.2018.03.055. Epub 2018 Mar 27.

DOI:10.1016/j.vaccine.2018.03.055
PMID:29602701
Abstract

The dengue virus (DENV) vaccines that are licensed or in clinical development consist of DENV serotype 1-4 tetravalent formulations given simultaneously and are not acquired sequentially like natural infections. It is unclear what effect this has on development of protective levels of immunity to all four serotypes. Serotype-specific neutralizing antibody (NAb) is considered the most relevant correlate of protection from dengue disease. Here we assessed levels of serotype-specific and cross-reactive NAb in immune sera from 10 subjects vaccinated with a live attenuated tetravalent DENV vaccine developed at the Walter Reed Army Institute of Research. The majority of subjects NAb responses to DENV-2 and DENV-4 were type-specific, while their NAb responses to DENV-1 and DENV-3 were primarily cross-reactive. Vaccine virus RNAemia has been most frequently detected for DENV-2 and DENV-4 in vaccinated subjects, strongly suggesting that replication is important for eliciting serotype-specific immunity.

摘要

登革病毒 (DENV) 疫苗已获得许可或正在临床开发中,由 DENV 血清型 1-4 四价制剂同时给药组成,而不是像自然感染那样顺序获得。目前尚不清楚这对所有四种血清型产生保护性免疫水平的效果如何。血清型特异性中和抗体 (NAb) 被认为是预防登革热疾病的最相关保护相关性。在这里,我们评估了在沃尔特·里德陆军研究所开发的减毒活四价 DENV 疫苗接种的 10 名受试者的免疫血清中的血清型特异性和交叉反应性 NAb 水平。大多数受试者对 DENV-2 和 DENV-4 的 NAb 反应是特异性的,而他们对 DENV-1 和 DENV-3 的 NAb 反应主要是交叉反应的。在接种疫苗的受试者中,最常检测到 DENV-2 和 DENV-4 的疫苗病毒 RNA 血症,这强烈表明复制对于引发血清型特异性免疫很重要。

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