Evidence map›Paper›PMID 40639194›Full record

ArticleTicks and tick-borne diseases2025

IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans.

Patrick H Kelly, Derek A T Cummings, Eva Iniguez, Tiago Donatelli, Luana Rogerio, Jan Kotál, Larissa Almeida Martins, Markus Berger, Lucas C Sousa-Paula, Stephen Lu and 5 more

Abstract read
In one paragraph

Article in Ticks and tick-borne diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Patrick H KellyGlobal Vaccines Medical Affairs, Pfizer Research & Development, NY, NY, USA.
Derek A T CummingsJohns Hopkins University, Baltimore, MD, USA.
Eva IniguezVector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USA.
Tiago DonatelliVector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USA.
Luana RogerioVector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USA.
Jan KotálTick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USA; Department of Medical Biology, Faculty of Science, University of South Bohemia in České Budějovice, Budweis, Czech Republic.
Larissa Almeida MartinsTick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USA; Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA.
Markus BergerTick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USA; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Lucas C Sousa-PaulaTick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USA.
Stephen LuTick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USA.
James H StarkGlobal Vaccines Medical Affairs, Pfizer Research & Development, Cambridge, MS, USA.
Siu-Ping NgLyme Disease Studies Unit, Laboratory of Clinical Immunology & Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
Adriana MarquesLyme Disease Studies Unit, Laboratory of Clinical Immunology & Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
Jesus G ValenzuelaGlobal Vaccines Medical Affairs, Pfizer Research & Development, NY, NY, USA; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USA.
Lucas TirloniGlobal Vaccines Medical Affairs, Pfizer Research & Development, NY, NY, USA; Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USA. Electronic address: lucas.tirloni@nih.gov.

Funding

Tick saliva and its importance for tick feeding and pathogen transmissionZIAAI001337 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TIRLONI, LUCAS · 2021 to 2025
$8.5M
Intramural NIH HHS Z99 AI999999Intramural NIH HHS ZIA AI001337
6 · The paper itself

Abstract

Ixodes scapularis is a primary vector of several important tick-borne pathogens including Borrelia burgdorferi sensu lato, the causative bacterial genospecies complex of Lyme disease, Babesia microti, Anaplasma phagocytophilum, Borrelia miyamotoi, Ehrlichia muris eauclarensis, and Powassan virus. Salivary compounds secreted by I. scapularis during blood feeding are immunogenic and can elicit robust antibody responses in humans which can potentially be leveraged as surrogate markers of prior tick bite exposure. In this study, we investigate the potential of a tick secreted salivary serine protease inhibitor, IxsS7, as a novel antigenic biomarker of I. scapularis exposure in humans. We demonstrate that the IxsS7 protein-coding sequence is highly conserved (>90 % identity) among other important Ixodes species (e.g., Ixodes ricinus, Ixodes persulcatus, and Ixodes pacificus) and poorly conserved (<50 % identity) with homologs from other tick genera, such as Amblyomma spp., Dermacentor spp., Rhipicephalus spp., and Haemaphysalis spp. Antibodies in sera from rabbits immunized with recombinant IxsS7 (rIxsS7) strongly recognize native IxsS7 when challenged with salivary gland homogenate (SGH) from blood-fed I. scapularis females, while showing minimal cross-reactivity with SGH from other hard tick (Ixodidae) genera. Western blot and ELISA analyses revealed that human subjects who reported recent prior exposure to ticks possessed IgG antibodies that recognized rIxsS7, highlighting its potential as a biomarker of exposure specifically against I. scapularis. Further development of serological tools that can measure human antibody responses to Ixodes-specific salivary antigens is essential to better quantify individual- and population-level risk of important tick-borne diseases such as Lyme disease.

Indexed as

Arthropod ProteinsIxodesSalivary Proteins and PeptidesTick BitesAnimalsBiomarkersFemaleHumansMaleArthropod ProteinsBiomarkersSalivary Proteins and PeptidesBorreliaIxodesIxodidLymeTickTick salivaVaccine

Identifiers

PMID40639194
PMCPMC12321155

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.