Science Translational Medicine March 2025. Ixodes scapularis 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. scapularis proteins secreted during feeding. To address this, we developed I. scapularis rapid extracellular antigen monitoring (IscREAM), a technique to detect antibody responses to more than 3000 tick antigens. We validated IscREAM 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. scapularis and defines immunogen candidates for future antitick vaccines.

Journal of Infectious Diseases, 2026. Lyme disease spirochetes are maintained in natural reservoirs before spilling over into human populations. Targeting these reservoirs with vaccinations or antibiotics could impact the Borrelia burgdorferi enzootic cycle and reduce the risk of human Lyme disease. In this work we report that the narrow-spectrum antibiotic hygromycin A is sufficient to disrupt B burgdorferi transmission from the main eastern US reservoir, Peromyscus leucopus, to ticks. Additionally, hygromycin A-containing baits can clear B burgdorferi from P leucopus. These studies lay the foundation for the use of hygromycin A as a reservoir-targeted antibiotic to eradicate B burgdorferi in the wild.

Many of the diverse tick-borne diseases (TBD) in the US appear to be increasing in incidence, leading to concern that factors such as climate change may create challenging scenarios. The 18 TBD and 1 syndrome that cause illnesses in US residents present varying public health burdens (Table). For US clinicians, the most common TBD of concern is Lyme disease (estimated at about 476 000 cases each year1), with babesiosis, human granulocytic anaplasmosis (HGA), Rocky Mountain spotted fever, monocytic ehrlichiosis (HME), and alpha gal allergy (ie, red meat allergy) annually accounting for hundreds to thousands of cases. The remaining TBD are either rare (≤50 cases/y) or diagnosed sporadically every few years, although some of these carry severe morbidity or mortality. TBD cases have increased within the last decade, but the cause for this trend is multifactorial. Changes in case reporting and case definitions have contributed to the increase,2 as have improved diagnostic capacity, demographic shifts, urbanization, and an expansion in the range and local abundance of tick vectors.

Survivors of Powassan encephalitis often have persistent neurological disease. A new mouse model replicates some...

Although laboratory strains of  Mus musculus mice have successfully been leveraged to model acute human Lyme disease,...

Borrelia burgdorferi (Bb), the causative agent of Lyme disease, establishes a long-term infection and leads to disease...