Tick feeding or vaccination with tick antigens elicits immunity to the <i>Ixodes scapularis</i> exoproteome in guinea pigs and humans.

Hart, Thomas M; Cui, Yingjun; Telford, Sam R; Marín-López, Alejandro; Calloway, Keith; Dai, Yile; Matias, Jaqueline; DePonte, Kathleen et al. · Sci Transl Med · 2025

basic_science · Level V

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Abstract

<i>Ixodes scapularis</i> is a primary vector of tick-borne pathogens in North America. Repeated exposure to these ticks can induce a humoral response to tick antigens and acquired tick resistance. However, identifying antigens contributing to this resistance is challenging because of the vast number of <i>I. scapularis</i> proteins secreted during feeding. To address this, we developed <i>I. scapularis</i> rapid extracellular antigen monitoring (<i>Isc</i>REAM), a technique to detect antibody responses to more than 3000 tick antigens. We validated <i>Isc</i>REAM with immunoglobulin G (IgG) from guinea pigs vaccinated with tick antigens, including a cement antigen cocktail that induced tick resistance. Furthermore, we explored the natural response to tick bites by profiling antigens recognized by IgG isolated from a tick-resistant individual, as well as from others with Lyme disease and tick-bitten guinea pigs and mice, to identify 199 recognized antigens. We observed that several antigens contained histamine-binding domains. This work enhances our understanding of the host immune response to <i>I. scapularis</i> and defines immunogen candidates for future antitick vaccines.

Medical subject headings