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 (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.

Development of a recombinant vaccine against human onchocerciasis

“…Statistical analyses did not reveal correlations between individual factors or groups of factors and the presence of protective immunity. Studies in the CC-RIX mice demonstrated that the bivalent co-administered vaccine composed of Advax-2-adjuvanted Ov-103 and Ov-RAL-2 was effective across a wide range of genetic backgrounds and suggests that the vaccine can induce several different types of protective immune mechanisms [113].…”

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

“…Mass spectrometry imaging (MSI), the combination of molecular mass analysis and spatial information, can provide information on the spatial distribution of endogenous and exogenous species in tissue sections, without the need to disrupt sample integrity [146,147]. It enables both untargeted and direct targeted investigations for the discovery of disease or host immune response-related biomarkers, although the sensitivity for intact macromolecules, such as proteins, is still limited [148,149]. Matrix-assisted laser desorption/ionization (MALDI) is the most popular ionization technique for MSI due to its ability to image a wide range of molecular weights and molecular species (e.g., metabolites and proteins).…”

“…However, alternative models such as genetically diverse mouse populations are well-suited for this application. For example, the Collaborative Cross constitutes a new experimental platform to investigate the influence of host genetic factors in the susceptibility to infectious diseases [237] and starts to be used to study vaccine-induced responses [148].…”

Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis

“…The Onchocerciasis Vaccine for Africa (TOVA) consortium aims to develop a prophylactic vaccine based on recombinant subunit antigens to support MDA programs. In recent years, two recombinant antigen candidates, Ov-103 and Ov-RAL-2, have emerged as leading vaccine candidates, showing promising results both in vitro and in small animal experimental infection models, including heterogenous outbred populations against O. volvulus, as well as in a gerbil-Brugia malayi model using B. malayi-specific recombinant 103 and RAL-2 homologues [16][17][18][19][20]. Importantly, these studies have also determined key immunological mechanisms associated with vaccine-induced protection.…”