Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice
Open Access
- 26 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in npj Vaccines
- Vol. 6 (1), 1-12
- https://doi.org/10.1038/s41541-020-00276-2
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.Keywords
Funding Information
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01 AI078314, R01 AI078314, R01 AI078314, HHS-N272201400053C, HHS-N272200800039C, U01-AI061142, R01 AI078314, R01 AI078314, R01 AI078314, R01 AI078314)
- UNC | UNC-Chapel Hill | Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (MCR012CCRI)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (P30 CA056036, P30 CA056036)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute
This publication has 70 references indexed in Scilit:
- Status and access to the Collaborative Cross populationMammalian Genome, 2012
- The Genome Architecture of the Collaborative Cross Mouse Genetic Reference PopulationGenetics, 2012
- Yellow fever vaccine induces integrated multilineage and polyfunctional immune responsesThe Journal of Experimental Medicine, 2008
- Host Genetic Factors and Vaccine-Induced Immunity to Hepatitis B Virus InfectionPLOS ONE, 2008
- Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin TreatmentPLoS Neglected Tropical Diseases, 2007
- The perfect mix: recent progress in adjuvant researchNature Reviews Microbiology, 2007
- Association between microfilarial load and excess mortality in onchocerciasis: an epidemiological studyThe Lancet, 2004
- Development of a Recombinant Antigen Vaccine against Infection with the Filarial WormOnchocerca volvulusInfection and Immunity, 2001
- Genetic Prediction of Nonresponse to Hepatitis B VaccineThe New England Journal of Medicine, 1989