关键词: RNA antibody dengue virus immunity monoclonal natural infection polyclonal sera structural targets vaccine

Mesh : Humans Antibodies, Viral Dengue Virus Antibodies, Neutralizing Dengue Vaccines Viral Envelope Proteins / genetics Glycoproteins Vaccination Dengue

来  源:   DOI:10.1016/j.chom.2023.10.004   PDF(Pubmed)

Abstract:
The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.
摘要:
在用四种不同的登革热病毒血清型(DENV1-4)中的任一种感染后,包膜(E)糖蛋白是类型特异性(TS)中和抗体(nAbs)的主要靶标。nAbs可以被引发到不同的结构E域(ED)I,II,或者III.然而,这些结构域特异性抗体的相对贡献尚不清楚.为了确定自然感染或疫苗接种后血清中的主要DENV3nAb靶标,嵌合DENV1重组编码DENV3EDI,EDII,或者产生了EDIII。DENV3EDII是TS多克隆nAb应答的主要靶标,并且编码两个或更多个中和表位。相比之下,一些是以受试者依赖的方式接种DENV3单价疫苗引发的针对每个ED的血清TSnAbs的个体,强调EDI和EDIII。疫苗应答也对DENV3基因型变异敏感。此DENV1/3面板允许测量血清EDTSnAbs,揭示自然感染或疫苗接种后TSnAb免疫的差异。
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