TY - JOUR
T1 - The Ixodes ricinus salivary gland proteome during feeding and B. Afzelii infection
T2 - New avenues for an anti-tick vaccine
AU - Klouwens, Michelle J.
AU - Trentelman, Jos J. A.
AU - Barriales, Diego
AU - Ersoz, Jasmin I.
AU - Azkargorta, Mikel
AU - Elortza, Felix
AU - Šíma, Radek
AU - Hajdušek, Ondrej
AU - Lavin, José-Luis
AU - Tomás Cortazar, Julen
AU - Escobes Corcuera, Iraide
AU - Colstrup, Emil
AU - Nayak, Abhijeet
AU - Martín Ruíz, Itziar
AU - Rodriguez, Hector
AU - Nijhof, Ard M.
AU - Anguita, Juan
AU - Hovius, Joppe W. R.
N1 - Funding Information: This project has received funding from the European Union’s Seventh Programme for research, technological development and demonstration under grant agreement No. 602272 of which JWH was the scientific coordinator. This work was also supported by a “Vidi” grant (09150171910024) from JWH received from The Netherlands Organisation for health research and development (ZonMw). RS and OH were supported from the grant Centre for Research of Pathogenicity and Virulence of Parasites (no. CZ.02.1.01/0.0/0.0/16_019/ 0000759), funded by the European Regional Development Fund (ERDF) and Ministry of Education, Youth, and Sport, Czech Republic (MEYS). AMN received financial support from the Federal Ministry of Education and Research (BMBF) under project number 01KI1720 as part of the ‘Research Network Zoonotic Infectious Diseases’. R.S. was supported by the Ministry of Health of the Czech Republic, grant no. NU20-05-00396, and by the Czech Science Foundation grant no. 22-30920S. Funding Information: This project has received funding from the European Union's Seventh Programme for research, technological development and demonstration under grant agreement No. 602272 of which JWH was the scientific coordinator. This work was also supported by a “Vidi” grant (09150171910024) from JWH received from The Netherlands Organisation for health research and development (ZonMw). RS and OH were supported from the grant Centre for Research of Pathogenicity and Virulence of Parasites (no. CZ.02.1.01/0.0/0.0/16_019/ 0000759), funded by the European Regional Development Fund (ERDF) and Ministry of Education, Youth, and Sport, Czech Republic (MEYS). AMN received financial support from the Federal Ministry of Education and Research (BMBF) under project number 01KI1720 as part of the ‘Research Network Zoonotic Infectious Diseases’. R.S. was supported by the Ministry of Health of the Czech Republic, grant no. NU20-05-00396, and by the Czech Science Foundation grant no. 22-30920S. Publisher Copyright: © 2023 The Author(s)
PY - 2023/3/17
Y1 - 2023/3/17
N2 - Introduction: Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis, are transmitted by Ixodes ticks. Tick saliva proteins are instrumental for survival of both the vector and spirochete and have been investigated as targets for vaccine targeting the vector. In Europe, the main vector for Lyme borreliosis is Ixodes ricinus, which predominantly transmits Borrelia afzelii. We here investigated the differential production of I. ricinus tick saliva proteins in response to feeding and B. afzelii infection. Method: Label-free Quantitative Proteomics and Progenesis QI software was used to identify, compare, and select tick salivary gland proteins differentially produced during tick feeding and in response to B. afzelii infection. Tick saliva proteins were selected for validation, recombinantly expressed and used in both mouse and guinea pig vaccination and tick-challenge studies. Results: We identified 870 I. ricinus proteins from which 68 were overrepresented upon 24-hours of feeding and B. afzelii infection. Selected tick proteins were successfully validated by confirming their expression at the RNA and native protein level in independent tick pools. When used in a recombinant vaccine formulation, these tick proteins significantly reduced the post-engorgement weights of I. ricinus nymphs in two experimental animal models. Despite the reduced ability of ticks to feed on vaccinated animals, we observed efficient transmission of B. afzelii to the murine host. Conclusion: Using quantitative proteomics, we identified differential protein production in I. ricinus salivary glands in response to B. afzelii infection and different feeding conditions. These results provide novel insights into the process of I. ricinus feeding and B. afzelii transmission and revealed novel candidates for an anti-tick vaccine.
AB - Introduction: Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis, are transmitted by Ixodes ticks. Tick saliva proteins are instrumental for survival of both the vector and spirochete and have been investigated as targets for vaccine targeting the vector. In Europe, the main vector for Lyme borreliosis is Ixodes ricinus, which predominantly transmits Borrelia afzelii. We here investigated the differential production of I. ricinus tick saliva proteins in response to feeding and B. afzelii infection. Method: Label-free Quantitative Proteomics and Progenesis QI software was used to identify, compare, and select tick salivary gland proteins differentially produced during tick feeding and in response to B. afzelii infection. Tick saliva proteins were selected for validation, recombinantly expressed and used in both mouse and guinea pig vaccination and tick-challenge studies. Results: We identified 870 I. ricinus proteins from which 68 were overrepresented upon 24-hours of feeding and B. afzelii infection. Selected tick proteins were successfully validated by confirming their expression at the RNA and native protein level in independent tick pools. When used in a recombinant vaccine formulation, these tick proteins significantly reduced the post-engorgement weights of I. ricinus nymphs in two experimental animal models. Despite the reduced ability of ticks to feed on vaccinated animals, we observed efficient transmission of B. afzelii to the murine host. Conclusion: Using quantitative proteomics, we identified differential protein production in I. ricinus salivary glands in response to B. afzelii infection and different feeding conditions. These results provide novel insights into the process of I. ricinus feeding and B. afzelii transmission and revealed novel candidates for an anti-tick vaccine.
KW - Anti-tick vaccines
KW - Borrelia afzelii
KW - Feeding
KW - Ixodes ricinus
KW - Proteomics
KW - Salivary glands
UR - http://www.scopus.com/inward/record.url?scp=85148363669&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.vaccine.2023.02.003
DO - https://doi.org/10.1016/j.vaccine.2023.02.003
M3 - Article
C2 - 36797101
SN - 0264-410X
VL - 41
SP - 1951
EP - 1960
JO - Vaccine
JF - Vaccine
IS - 12
ER -