Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice

盘尾丝虫双价亚单位疫苗在遗传多样性协作杂交重组近交系杂交小鼠中诱导保护性免疫

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作者:Nathan M Ryan #, Jessica A Hess #, Fernando Pardo-Manuel de Villena, Benjamin E Leiby, Ayako Shimada, Lei Yu, Amir Yarmahmoodi, Nikolai Petrovsky, Bin Zhan, Maria Elena Bottazzi, Benjamin L Makepeace, Sara Lustigman, David Abraham

Abstract

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.

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