Abstract
The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.
Highlights
Helminth infections pose a massive burden on human and animal health worldwide
Similar to the observations made in study 1, animals from study 2 vaccinated with native ASP (nASP)+QuilA vaccine showed a reduction of 42% in cumulative faecal egg counts (FEC) compared with the control vaccinated group, whereas no reduction of FEC was observed in the pASP+QuilA and nASP+Al(OH)[3] vaccinated groups (Supplemental Fig. 1B)
natural killer (NK) cells were the major cell population found in nASP+QuilA vaccinated animals which proliferated following re-stimulation of mononuclear cells (MNCs) from the abomasal draining lymph nodes (LNs) or spleen of cattle and mice, respectively
Summary
Helminth infections pose a massive burden on human and animal health worldwide. Despite the widespread development of drug resistant worms, anthelmintic treatment still remains the main method to control these infections[1,2]. A promising vaccine against the blood feeding nematode Haemonchus contortus in sheep, based on native antigens isolated from adult worms, was commercialized[8]. Mimicking the protective response by recombinant antigens would provide a major breakthrough in parasite vaccine development This approach has already proven successful for the production of protective vaccines against the cestodes Taenia saginata and Echinococcus granulosus[9], and the nematode Teladorsagia circumcincta[10], it has been unsuccessful in many other cases[11]. The overall aim of the present study was to analyse and compare the effect of both antigen (native vs recombinant) and adjuvant (QuilA vs Al(OH)3) on the cellular and humoral vaccine-induced immune responses
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