IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans
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. Sa...
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Elsevier
2025-07-01
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| Series: | Ticks and Tick-Borne Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1877959X25000780 |
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| author | 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 James H. Stark Siu-Ping Ng Adriana Marques Jesus G. Valenzuela Lucas Tirloni |
| author_facet | 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 James H. Stark Siu-Ping Ng Adriana Marques Jesus G. Valenzuela Lucas Tirloni |
| author_sort | Patrick H. Kelly |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2357253c027241648c99bb8d214e6aa4 |
| institution | Kabale University |
| issn | 1877-9603 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ticks and Tick-Borne Diseases |
| spelling | doaj-art-2357253c027241648c99bb8d214e6aa42025-08-20T03:32:23ZengElsevierTicks and Tick-Borne Diseases1877-96032025-07-0116410251410.1016/j.ttbdis.2025.102514IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humansPatrick H. Kelly0Derek A.T. Cummings1Eva Iniguez2Tiago Donatelli3Luana Rogerio4Jan Kotál5Larissa Almeida Martins6Markus Berger7Lucas C Sousa-Paula8Stephen Lu9James H. Stark10Siu-Ping Ng11Adriana Marques12Jesus G. Valenzuela13Lucas Tirloni14Global Vaccines Medical Affairs, Pfizer Research & Development, NY, NY, USAJohns Hopkins University, Baltimore, MD, USAVector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USAVector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USAVector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USATick-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 RepublicTick-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, USATick-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, BrazilTick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USATick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Hamilton, MT, USAGlobal Vaccines Medical Affairs, Pfizer Research & Development, Cambridge, MS, USALyme Disease Studies Unit, Laboratory of Clinical Immunology & Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USALyme Disease Studies Unit, Laboratory of Clinical Immunology & Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USAGlobal 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, USAGlobal Vaccines Medical Affairs, Pfizer Research & Development, NY, NY, USA; Corresponding author at: Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), 903 S 4th Street, Hamilton, MT 59840, 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, USAIxodes 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.http://www.sciencedirect.com/science/article/pii/S1877959X25000780IxodesBorreliaTickLymeTick salivaVaccine |
| spellingShingle | 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 James H. Stark Siu-Ping Ng Adriana Marques Jesus G. Valenzuela Lucas Tirloni IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans Ticks and Tick-Borne Diseases Ixodes Borrelia Tick Lyme Tick saliva Vaccine |
| title | IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans |
| title_full | IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans |
| title_fullStr | IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans |
| title_full_unstemmed | IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans |
| title_short | IxsS7: A novel biomarker for Ixodes scapularis tick bite exposure in humans |
| title_sort | ixss7 a novel biomarker for ixodes scapularis tick bite exposure in humans |
| topic | Ixodes Borrelia Tick Lyme Tick saliva Vaccine |
| url | http://www.sciencedirect.com/science/article/pii/S1877959X25000780 |
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