Ryan Nathan M, Hess Jessica A, de Villena Fernando Pardo-Manuel, Leiby Benjamin E, Shimada Ayako, Yu Lei, Yarmahmoodi Amir, Petrovsky Nikolai, Zhan Bin, Bottazzi Maria Elena, Makepeace Benjamin L, Lustigman Sara, Abraham David
Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
NPJ Vaccines. 2021 Jan 26;6(1):17. doi: 10.1038/s41541-020-00276-2.
This study tests the hypothesis that an Onchocerca volvulus vaccine, consisting of two recombinant antigens (Ov-103 and Ov-RAL-2) formulated with the combination-adjuvant Advax-2, can induce protective immunity in genetically diverse Collaborative Cross recombinant inbred intercross mice (CC-RIX). CC-RIX lines were immunized with the O. volvulus vaccine and challenged with third-stage larvae. Equal and significant reductions in parasite survival were observed in 7 of 8 CC-RIX lines. Innate protective immunity was seen in the single CC-RIX line that did not demonstrate protective adaptive immunity. Analysis of a wide array of immune factors showed that each line of mice have a unique set of immune responses to vaccination and challenge suggesting that the vaccine is polyfunctional, inducing different equally-protective sets of immune responses based on the genetic background of the immunized host. Vaccine efficacy in genetically diverse mice suggests that it will also be effective in genetically complex human populations.
由两种重组抗原(Ov-103和Ov-RAL-2)与复合佐剂Advax-2配制而成的盘尾丝虫疫苗,可在基因多样的协作杂交重组近交系互交小鼠(CC-RIX)中诱导保护性免疫。用盘尾丝虫疫苗对CC-RIX品系进行免疫,并以第三期幼虫进行攻毒。在8个CC-RIX品系中的7个品系中观察到寄生虫存活率同等且显著降低。在未表现出保护性适应性免疫的单个CC-RIX品系中观察到固有保护性免疫。对一系列免疫因子的分析表明,每一行小鼠对疫苗接种和攻毒都有一套独特的免疫反应,这表明该疫苗具有多功能性,基于免疫宿主的遗传背景诱导不同但同样具有保护作用的免疫反应组合。该疫苗在基因多样的小鼠中的有效性表明,它在基因复杂的人群中也将有效。