Abstract
In Europe, Ixodes ricinus is the most important vector of human infectious diseases, most notably Lyme borreliosis and tick-borne encephalitis virus. Multiple non-natural hosts of I. ricinus have shown to develop immunity after repeated tick bites. Tick immunity has also been shown to impair B. burgdorferi transmission. Most interestingly, multiple tick bites reduced the likelihood of contracting Lyme borreliosis in humans. A vaccine that mimics tick immunity could therefore potentially prevent Lyme borreliosis in humans. A yeast surface display library (YSD) of nymphal I. ricinus salivary gland genes expressed at 24, 48 and 72 h into tick feeding was constructed and probed with antibodies from humans repeatedly bitten by ticks, identifying twelve immunoreactive tick salivary gland proteins (TSGPs). From these, three proteins were selected for vaccination studies. An exploratory vaccination study in cattle showed an anti-tick effect when all three antigens were combined. However, immunization of rabbits did not provide equivalent levels of protection. Our results show that YSD is a powerful tool to identify immunodominant antigens in humans exposed to tick bites, yet vaccination with the three selected TSGPs did not provide protection in the present form. Future efforts will focus on exploring the biological functions of these proteins, consider alternative systems for recombinant protein generation and vaccination platforms and assess the potential of the other identified immunogenic TSGPs.
Highlights
In Europe, Ixodes ricinus is the most important vector of human infectious diseases, most notably Lyme borreliosis and tick-borne encephalitis virus
We here describe multiple immunogenic tick saliva proteins identified through a novel yeast surface display expressing I. ricinus salivary gland proteins from nymphal ticks, which was probed with total IgG from humans that were repeatedly exposed to tick bites, or controls
3 successive selection rounds were performed using Magnetic-activated cell sorting (MACS) to isolate yeast cells expressing tick salivary gland proteins (TSGPs) recognized by human 20 TB IgG increasing the percentage induced SGP-yeast surface display library (YSD) positive cells, for both the expression marker Xpress and 20 TB IgG, from 1% to approximately 15% (Fig. 1a)
Summary
In Europe, Ixodes ricinus is the most important vector of human infectious diseases, most notably Lyme borreliosis and tick-borne encephalitis virus. infection[29,30] here, antibodies play an important role; passive transfer of IgG from animals repeatedly infested with I. scapularis nymphs for 24 h and that developed tick immunity partially protected naive animals against B. burgdorferi s.s. infection[31]. As part of the current study, we set out to identify I. ricinus tick salivary gland proteins recognized by antibodies of repeatedly tick-exposed humans and tested their potential to induce tick immunity. We here describe multiple immunogenic tick saliva proteins identified through a novel yeast surface display expressing I. ricinus salivary gland proteins from nymphal ticks, which was probed with total IgG from humans that were repeatedly exposed to tick bites, or controls. We have assessed the potential of the recombinant forms of selected tick saliva proteins as candidates for an anti-tick vaccine in three different experimental models
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