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

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 (C...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2021-01-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-020-00276-2
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author 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
author_facet 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
author_sort Nathan M. Ryan
collection DOAJ
description 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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spelling doaj.art-81bbb94a2d7b4f9fa3b415ead7d31ec92023-11-02T09:21:22ZengNature Portfolionpj Vaccines2059-01052021-01-016111210.1038/s41541-020-00276-2Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross miceNathan M. Ryan0Jessica A. Hess1Fernando Pardo-Manuel de Villena2Benjamin E. Leiby3Ayako Shimada4Lei Yu5Amir Yarmahmoodi6Nikolai Petrovsky7Bin Zhan8Maria Elena Bottazzi9Benjamin L. Makepeace10Sara Lustigman11David Abraham12Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina–Chapel HillDivision of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson UniversityDivision of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson UniversityFlow Cytometry Core Facility, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFlow Cytometry Core Facility, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityVaxine Pty Ltd, Flinders UniversityDepartment of Pediatrics, National School of Tropical Medicine, Baylor College of MedicineDepartment of Pediatrics, National School of Tropical Medicine, Baylor College of MedicineInstitute of Infection, Veterinary & Ecological Sciences, University of LiverpoolLaboratory of Molecular Parasitology, Lindsey F. Kimball Research Institute, New York Blood CenterDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityAbstract 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.https://doi.org/10.1038/s41541-020-00276-2
spellingShingle 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
Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
npj Vaccines
title Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
title_full Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
title_fullStr Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
title_full_unstemmed Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
title_short Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
title_sort onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
url https://doi.org/10.1038/s41541-020-00276-2
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