• This record comes from PubMed

Novel targets and strategies to combat borreliosis

. 2020 Mar ; 104 (5) : 1915-1925. [epub] 20200117

Language English Country Germany Media print-electronic

Document type Journal Article, Review

Grant support
17-21244S Grantová Agentura České Republiky
602272-2 European Union FP7 project ANTIDotE

Links

PubMed 31953560
PubMed Central PMC7222997
DOI 10.1007/s00253-020-10375-8
PII: 10.1007/s00253-020-10375-8
Knihovny.cz E-resources

Lyme borreliosis is a bacterial infection that can be spread to humans by infected ticks and may severely affect many organs and tissues. Nearly four decades have elapsed since the discovery of the disease agent called Borrelia burgdorferi. Although there is a plethora of knowledge on the infectious agent and thousands of scientific publications, an effective way on how to combat and prevent Lyme borreliosis has not been found yet. There is no vaccine for humans available, and only one active vaccine program in clinical development is currently running. A spirited search for possible disease interventions is of high public interest as surveillance data indicates that the number of cases of Lyme borreliosis is steadily increasing in Europe and North America. This review provides a condensed digest of the history of vaccine development up to new promising vaccine candidates and strategies that are targeted against Lyme borreliosis, including elements of the tick vector, the reservoir hosts, and the Borrelia pathogen itself.

See more in PubMed

Andre F, Booy R, Bock H, Clemens J, Datta S, John T, Lee B, Lolekha S, Peltola H, Ruff T, Santosham M, Schmitt H. Vaccination greatly reduces disease, disability, death and inequity worldwide. Bull World Health Organ. 2008;86:140–146. doi: 10.2471/BLT.07.040089. PubMed DOI PMC

Anguita J, Ramamoorthi N, Hovius JWR, Das S, Thomas V, Persinski R, Conze D, Askenase PW, Rincón M, Kantor FS, Fikrig E. Salp15, an Ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. Immunity. 2002;16:849–859. doi: 10.1016/S1074-7613(02)00325-4. PubMed DOI

Auwaerter PG, Melia MT. Bullying Borrelia: when the culture of science is under attack. Trans Am Clin Climatol Assoc. 2012;123:79–90. PubMed PMC

Baker PJ, Wormser GP. The clinical relevance of studies on Borrelia burgdorferi persisters. Am J Med. 2017;130:1009–1010. doi: 10.1016/j.amjmed.2017.04.014. PubMed DOI

Bensaci M, Bhattacharya D, Clark R, Hu LT. Oral vaccination with vaccinia virus expressing the tick antigen subolesin inhibits tick feeding and transmission of Borrelia burgdorferi. Vaccine. 2012;30:6040–6046. doi: 10.1016/j.vaccine.2012.07.053. PubMed DOI PMC

Brown EL, Kim JH, Reisenbichler ES, Höök M. Multicomponent Lyme vaccine: three is not a crowd. Vaccine. 2005;23:3687–3696. doi: 10.1016/j.vaccine.2005.02.006. PubMed DOI

Buchthal J, Evans SW, Lunshof J, Telford SR, Esvelt KM. Mice against ticks: an experimental community-guided effort to prevent tick-borne disease by altering the shared environment. Philos Trans R Soc Lond Ser B Biol Sci. 2019;374:20180105. doi: 10.1098/rstb.2018.0105. PubMed DOI PMC

Cabezas-Cruz A, de la Fuente J. Immunity to α-gal: toward a single-antigen pan-vaccine to control major infectious diseases. ACS Cent Sci. 2017;3:1140–1142. doi: 10.1021/acscentsci.7b00517. PubMed DOI PMC

Cadavid D, O’Neill T, Schaefer H, Pachner AR. Localization of Borrelia burgdorferi in the nervous system and other organs in a nonhuman primate model of Lyme disease. Lab Investig J Tech Methods Pathol. 2000;80:1043–1054. doi: 10.1038/labinvest.3780109. PubMed DOI

Cassatt DR, Patel NK, Ulbrandt ND, Hanson MS. DbpA, but not OspA, is expressed by Borrelia burgdorferi during spirochetemia and is a target for protective antibodies. Infect Immun. 1998;66:5379–5387. doi: 10.1128/IAI.66.11.5379-5387.1998. PubMed DOI PMC

Chmelar J, Oliveira CJ, Rezacova P, Francischetti IMB, Kovarova Z, Pejler G, Kopacek P, Ribeiro JMC, Mares M, Kopecky J, Kotsyfakis M. A tick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation. Blood. 2011;117:736–744. doi: 10.1182/blood-2010-06-293241. PubMed DOI PMC

Cinco M, Ruscio M, Rapagna F. Evidence of Dbps (decorin binding proteins) among European strains of Borrelia burgdorferi sensu lato and in the immune response of LB patient sera. FEMS Microbiol Lett. 2000;183:111–114. doi: 10.1111/j.1574-6968.2000.tb08942.x. PubMed DOI

Comstedt P, Schüler W, Meinke A, Lundberg U. The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes. PLoS One. 2017;12:e0184357. doi: 10.1371/journal.pone.0184357. PubMed DOI PMC

Connally NP, Durante AJ, Yousey-Hindes KM, Meek JI, Nelson RS, Heimer R. Peridomestic Lyme disease prevention: results of a population-based case-control study. Am J Prev Med. 2009;37:201–206. doi: 10.1016/j.amepre.2009.04.026. PubMed DOI

Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E. Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the Lyme disease agent. PLoS Pathog. 2010;6:e1001205. doi: 10.1371/journal.ppat.1001205. PubMed DOI PMC

de la Fuente J, Almazán C, Canales M, Pérez de la Lastra JM, Kocan KM, Willadsen P. A ten-year review of commercial vaccine performance for control of tick infestations on cattle. Anim Health Res Rev. 2007;8:23–28. doi: 10.1017/S1466252307001193. PubMed DOI

de la Fuente J, Pacheco I, Villar M, Cabezas-Cruz A. The alpha-gal syndrome: new insights into the tick-host conflict and cooperation. Parasit Vectors. 2019;12:154. doi: 10.1186/s13071-019-3413-z. PubMed DOI PMC

De Meneghi D, Stachurski F, Adakal H. Experiences in tick control by acaricide in the traditional cattle sector in Zambia and Burkina Faso: possible environmental and public health implications. Front Public Health. 2016;4:239. doi: 10.3389/fpubh.2016.00239. PubMed DOI PMC

del Rio B, Dattwyler RJ, Aroso M, Neves V, Meirelles L, Seegers JFML, Gomes-Solecki M. Oral immunization with recombinant Lactobacillus plantarum induces a protective immune response in mice with Lyme disease. Clin Vaccine Immunol CVI. 2008;15:1429–1435. doi: 10.1128/CVI.00169-08. PubMed DOI PMC

Diuk-Wasser MA, Hoen AG, Cislo P, Brinkerhoff R, Hamer SA, Rowland M, Cortinas R, Vourc’h G, Melton F, Hickling GJ, Tsao JI, Bunikis J, Barbour AG, Kitron U, Piesman J, Fish D. Human risk of infection with Borrelia burgdorferi, the Lyme disease agent, in eastern United States. Am J Trop Med Hyg. 2012;86:320–327. doi: 10.4269/ajtmh.2012.11-0395. PubMed DOI PMC

Earnhart CG, Buckles EL, Marconi RT. Development of an OspC-based tetravalent, recombinant, chimeric vaccinogen that elicits bactericidal antibody against diverse Lyme disease spirochete strains. Vaccine. 2007;25:466–480. doi: 10.1016/j.vaccine.2006.07.052. PubMed DOI

Earnhart CG, Marconi RT. An octavalent Lyme disease vaccine induces antibodies that recognize all incorporated OspC type-specific sequences. Hum Vaccin. 2007;3:281–289. doi: 10.4161/hv.4661. PubMed DOI

Ebady R, Niddam AF, Boczula AE, Kim YR, Gupta N, Tang TT, Odisho T, Zhi H, Simmons CA, Skare JT, Moriarty TJ. Biomechanics of Borrelia burgdorferi vascular interactions. Cell Rep. 2016;16:2593–2604. doi: 10.1016/j.celrep.2016.08.013. PubMed DOI PMC

Feng J, Wang T, Shi W, Zhang S, Sullivan D, Auwaerter PG, Zhang Y. Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library. Emerg Microbes Infect. 2014;3:e49. doi: 10.1038/emi.2014.53. PubMed DOI PMC

Feng J, Weitner M, Shi W, Zhang S, Sullivan D, Zhang Y. Identification of additional anti-persister activity against Borrelia burgdorferi from an FDA drug library. Antibiotics. 2015;4:397–410. doi: 10.3390/antibiotics4030397. PubMed DOI PMC

Fikrig E, Barthold SW, Kantor FS, Flavell RA. Protection of mice from Lyme borreliosis by oral vaccination with Escherichia coli expressing OspA. J Infect Dis. 1991;164:1224–1227. doi: 10.1093/infdis/164.6.1224. PubMed DOI

Fikrig Erol, Feng Wen, Barthold Stephen W., Telford Sam R., Flavell Richard A. Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission. The Journal of Immunology. 2000;164(10):5344–5351. doi: 10.4049/jimmunol.164.10.5344. PubMed DOI

Fikrig E, Pal U, Chen M, Anderson JF, Flavell RA. OspB antibody prevents Borrelia burgdorferi colonization of Ixodes scapularis. Infect Immun. 2004;72:1755–1759. doi: 10.1128/iai.72.3.1755-1759.2004. PubMed DOI PMC

Gilmore RD, Kappel KJ, Dolan MC, Burkot TR, Johnson BJ. Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC. Infect Immun. 1996;64:2234–2239. doi: 10.1128/IAI.64.6.2234-2239.1996. PubMed DOI PMC

Gomes-Solecki MJC, Brisson DR, Dattwyler RJ. Oral vaccine that breaks the transmission cycle of the Lyme disease spirochete can be delivered via bait. Vaccine. 2006;24:4440–4449. doi: 10.1016/j.vaccine.2005.08.089. PubMed DOI

Grimm D, Tilly K, Byram R, Stewart PE, Krum JG, Bueschel DM, Schwan TG, Policastro PF, Elias AF, Rosa PA. Outer-surface protein C of the Lyme disease spirochete: a protein induced in ticks for infection of mammals. Proc Natl Acad Sci U S A. 2004;101:3142–3147. doi: 10.1073/pnas.0306845101. PubMed DOI PMC

Hanson MS, Cassatt DR, Guo BP, Patel NK, McCarthy MP, Dorward DW, Höök M. Active and passive immunity against Borrelia burgdorferi decorin binding protein a (DbpA) protects against infection. Infect Immun. 1998;66:2143–2153. doi: 10.1128/IAI.66.5.2143-2153.1998. PubMed DOI PMC

Hanson MS, Patel NK, Cassatt DR, Ulbrandt ND. Evidence for vaccine synergy between Borrelia burgdorferi decorin binding protein a and outer surface protein a in the mouse model of Lyme borreliosis. Infect Immun. 2000;68:6457–6460. doi: 10.1128/IAI.68.11.6457-6460.2000. PubMed DOI PMC

Heikkilä T, Seppälä I, Saxén H, Panelius J, Peltomaa M, Julin T, Carlsson S-A, Lahdenne P. Recombinant BBK32 protein in serodiagnosis of early and late Lyme borreliosis. J Clin Microbiol. 2002;40:1174–1180. doi: 10.1128/JCM.40.4.1174-1180.2002. PubMed DOI PMC

Hinckley AF, Meek JI, Ray JAE, Niesobecki SA, Connally NP, Feldman KA, Jones EH, Backenson PB, White JL, Lukacik G, Kay AB, Miranda WP, Mead PS. Effectiveness of residential acaricides to prevent Lyme and other tick-borne diseases in humans. J Infect Dis. 2016;214:182–188. doi: 10.1093/infdis/jiv775. PubMed DOI PMC

Hovius JWR, de Jong MAWP, den Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TBH. Salp15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and mRNA stabilization. PLoS Pathog. 2008;4:e31. doi: 10.1371/journal.ppat.0040031. PubMed DOI PMC

Hubálek Z. Epidemiology of Lyme borreliosis. Curr Probl Dermatol. 2009;37:31–50. doi: 10.1159/000213069. PubMed DOI

Humair PF, Rais O, Gern L. Transmission of Borrelia afzelii from Apodemus mice and Clethrionomys voles to Ixodes ricinus ticks: differential transmission pattern and overwintering maintenance. Parasitology. 1999;118(Pt 1):33–42. doi: 10.1017/s0031182098003564. PubMed DOI

Jore S, Vanwambeke SO, Viljugrein H, Isaksen K, Kristoffersen AB, Woldehiwet Z, Johansen B, Brun E, Brun-Hansen H, Westermann S, Larsen I-L, Ytrehus B, Hofshagen M. Climate and environmental change drives Ixodes ricinus geographical expansion at the northern range margin. Parasit Vectors. 2014;7:11. doi: 10.1186/1756-3305-7-11. PubMed DOI PMC

Jore S, Viljugrein H, Hofshagen M, Brun-Hansen H, Kristoffersen AB, Nygård K, Brun E, Ottesen P, Sævik BK, Ytrehus B. Multi-source analysis reveals latitudinal and altitudinal shifts in range of Ixodes ricinus at its northern distribution limit. Parasit Vectors. 2011;4:84. doi: 10.1186/1756-3305-4-84. PubMed DOI PMC

Jutras BL, Lochhead RB, Kloos ZA, Biboy J, Strle K, Booth CJ, Govers SK, Gray J, Schumann P, Vollmer W, Bockenstedt LK, Steere AC, Jacobs-Wagner C. Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A. 2019;116:13498–13507. doi: 10.1073/pnas.1904170116. PubMed DOI PMC

Kalmár Z, Mihalca AD, Dumitrache MO, Gherman CM, Magdaş C, Mircean V, Oltean M, Domşa C, Matei IA, Mărcuţan DI, Sándor AD, D’Amico G, Paştiu A, Györke A, Gavrea R, Marosi B, Ionică A, Burkhardt E, Toriay H, Cozma V. Geographical distribution and prevalence of Borrelia burgdorferi genospecies in questing Ixodes ricinus from Romania: a countrywide study. Ticks Tick-Borne Dis. 2013;4:403–408. doi: 10.1016/j.ttbdis.2013.04.007. PubMed DOI

Keirans JE, Clifford CM, Hoogstraal H, Easton ER. Discovery of Nuttalliella namaqua Bedford (Acarina: Ixodoidea: Nuttalliellidae) in Tanzania and redescription of the female based on scanning electron microcopy. Ann Entomol Soc Am. 1976;69:926–932. doi: 10.1093/aesa/69.5.926. DOI

Krupka I, Straubinger RK. Lyme borreliosis in dogs and cats: background, diagnosis, treatment and prevention of infections with Borrelia burgdorferi sensu stricto. Vet Clin North Am Small Anim Pract. 2010;40:1103–1119. doi: 10.1016/j.cvsm.2010.07.011. PubMed DOI

Kuehn BM. CDC estimates 300,000 US cases of Lyme disease annually. JAMA. 2013;310:1110. doi: 10.1001/jama.2013.278331. PubMed DOI

Kung F, Kaur S, Smith AA, Yang X, Wilder CN, Sharma K, Buyuktanir O, Pal U. A Borrelia burgdorferi surface-exposed transmembrane protein lacking detectable immune responses supports pathogen persistence and constitutes a vaccine target. J Infect Dis. 2016;213:1786–1795. doi: 10.1093/infdis/jiw013. PubMed DOI PMC

Kunz SE, Kemp DH. Insecticides and acaricides: resistance and environmental impact. Rev Sci Tech Int Off Epizoot. 1994;13:1249–1286. doi: 10.20506/rst.13.4.816. PubMed DOI

Lahdenne P, Sarvas H, Kajanus R, Eholuoto M, Sillanpää H, Seppälä I. Antigenicity of borrelial protein BBK32 fragments in early Lyme borreliosis. J Med Microbiol. 2006;55:1499–1504. doi: 10.1099/jmm.0.46621-0. PubMed DOI

Lascher S, Goldmann DR. Efficacy of antibiotic prophylaxis for the prevention of Lyme disease after tick bite. Am J Med. 2016;129:935–937. doi: 10.1016/j.amjmed.2016.05.011. DOI

Lawrenz MB, Wooten RM, Norris SJ. Effects of vlsE complementation on the infectivity of Borrelia burgdorferi lacking the linear plasmid lp28-1. Infect Immun. 2004;72:6577–6585. doi: 10.1128/IAI.72.11.6577-6585.2004. PubMed DOI PMC

Lee J, Wormser GP. Pharmacodynamics of doxycycline for chemoprophylaxis of Lyme disease: preliminary findings and possible implications for other antimicrobials. Int J Antimicrob Agents. 2008;31:235–239. doi: 10.1016/j.ijantimicag.2007.11.011. PubMed DOI

Ljøstad U, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, Mygland A. Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial. Lancet Neurol. 2008;7:690–695. doi: 10.1016/S1474-4422(08)70119-4. PubMed DOI

Luke CJ, Huebner RC, Kasmiersky V, Barbour AG. Oral delivery of purified lipoprotein OspA protects mice from systemic infection with Borrelia burgdorferi. Vaccine. 1997;15:739–746. doi: 10.1016/s0264-410x(97)00219-3. PubMed DOI

Margos G, Fingerle V, Reynolds S. Borrelia bavariensis: vector switch, niche invasion, and geographical spread of a tick-borne bacterial parasite. Front Ecol Evol. 2019;7:401. doi: 10.3389/fevo.2019.00401. DOI

Melo R, Richer L, Johnson DL, Gomes-Solecki M. Oral immunization with OspC does not prevent tick-borne Borrelia burgdorferi infection. PLoS One. 2016;11:e0151850. doi: 10.1371/journal.pone.0151850. PubMed DOI PMC

Middelveen MJ, Sapi E, Burke J, Filush KR, Franco A, Fesler MC, Stricker RB. Persistent Borrelia infection in patients with ongoing symptoms of Lyme disease. Healthcare. 2018;6:2. doi: 10.3390/healthcare6020033. PubMed DOI PMC

Montgomery RR, Schreck K, Wang X, Malawista SE. Human neutrophil calprotectin reduces the susceptibility of Borrelia burgdorferi to penicillin. Infect Immun. 2006;74:2468–2472. doi: 10.1128/IAI.74.4.2468-2472.2006. PubMed DOI PMC

Moriarty TJ, Norman MU, Colarusso P, Bankhead T, Kubes P, Chaconas G. Real-time high resolution 3D imaging of the Lyme disease spirochete adhering to and escaping from the vasculature of a living host. PLoS Pathog. 2008;4:e1000090. doi: 10.1371/journal.ppat.1000090. PubMed DOI PMC

Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Agüero-Rosenfeld ME, Dennis DT, Wormser GP, Tick Bite Study Group Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345:79–84. doi: 10.1056/NEJM200107123450201. PubMed DOI

Narasimhan S, Schuijt TJ, Abraham NM, Rajeevan N, Coumou J, Graham M, Robson A, Wu M-J, Daffre S, Hovius JW, Fikrig E. Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization. Nat Commun. 2017;8:184. doi: 10.1038/s41467-017-00208-0. PubMed DOI PMC

Nigrovic LE, Thompson KM. The Lyme vaccine: a cautionary tale. Epidemiol Infect. 2007;135:1–8. doi: 10.1017/S0950268806007096. PubMed DOI PMC

Norman MU, Moriarty TJ, Dresser AR, Millen B, Kubes P, Chaconas G. Molecular mechanisms involved in vascular interactions of the Lyme disease pathogen in a living host. PLoS Pathog. 2008;4:e1000169. doi: 10.1371/journal.ppat.1000169. PubMed DOI PMC

Nuttall PA (2019) Tick saliva and its role in pathogen transmission. Wien Klin Wochenschr:1–12. 10.1007/s00508-019-1500-y PubMed PMC

Nuttall PA, Labuda M. Tick-host interactions: saliva-activated transmission. Parasitology. 2004;129(Suppl):S177–S189. doi: 10.1017/s0031182004005633. PubMed DOI

Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, Desilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, Fikrig E. TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi. Cell. 2004;119:457–468. doi: 10.1016/j.cell.2004.10.027. PubMed DOI

Parola P, Raoult D. Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis Off Publ Infect Dis Soc Am. 2001;32:897–928. doi: 10.1086/319347. PubMed DOI

Perez G, Bastian S, Agoulon A, Bouju A, Durand A, Faille F, Lebert I, Rantier Y, Plantard O, Butet A. Effect of landscape features on the relationship between Ixodes ricinus ticks and their small mammal hosts. Parasit Vectors. 2016;9:20. doi: 10.1186/s13071-016-1296-9. PubMed DOI PMC

Perner J, Kropáčková S, Kopáček P, Ribeiro JMC. Sialome diversity of ticks revealed by RNAseq of single tick salivary glands. PLoS Negl Trop Dis. 2018;12:e0006410. doi: 10.1371/journal.pntd.0006410. PubMed DOI PMC

Piesman J, Hojgaard A, Ullmann AJ, Dolan MC. Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted Lyme disease spirochete infection in a murine model. Antimicrob Agents Chemother. 2014;58:348–351. doi: 10.1128/AAC.01932-13. PubMed DOI PMC

Pothineni VR, Wagh D, Babar MM, Inayathullah M, Solow-Cordero D, Kim K-M, Samineni AV, Parekh MB, Tayebi L, Rajadas J. Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening. Drug Des Devel Ther. 2016;10:1307–1322. doi: 10.2147/DDDT.S101486. PubMed DOI PMC

Probert WS, Johnson BJ. Identification of a 47 kDa fibronectin-binding protein expressed by Borrelia burgdorferi isolate B31. Mol Microbiol. 1998;30:1003–1015. doi: 10.1046/j.1365-2958.1998.01127.x. PubMed DOI

Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature. 2005;436:573–577. doi: 10.1038/nature03812. PubMed DOI PMC

Rand PW, Lubelczyk C, Holman MS, Lacombe EH, Smith RP. Abundance of Ixodes scapularis (Acari: Ixodidae) after the complete removal of deer from an isolated offshore island, endemic for Lyme disease. J Med Entomol. 2004;41:779–784. doi: 10.1603/0022-2585-41.4.779. PubMed DOI

Rego ROM, Trentelman JJA, Anguita J, Nijhof AM, Sprong H, Klempa B, Hajdusek O, Tomás-Cortázar J, Azagi T, Strnad M, Knorr S, Sima R, Jalovecka M, Fumačová Havlíková S, Ličková M, Sláviková M, Kopacek P, Grubhoffer L, Hovius JW. Counterattacking the tick bite: towards a rational design of anti-tick vaccines targeting pathogen transmission. Parasit Vectors. 2019;12:229. doi: 10.1186/s13071-019-3468-x. PubMed DOI PMC

Ribeiro JM, Mather TN, Piesman J, Spielman A. Dissemination and salivary delivery of Lyme disease spirochetes in vector ticks (Acari: Ixodidae) J Med Entomol. 1987;24:201–205. doi: 10.1093/jmedent/24.2.201. PubMed DOI

Richer LM, Brisson D, Melo R, Ostfeld RS, Zeidner N, Gomes-Solecki M. Reservoir targeted vaccine against Borrelia burgdorferi: a new strategy to prevent Lyme disease transmission. J Infect Dis. 2014;209:1972–1980. doi: 10.1093/infdis/jiu005. PubMed DOI PMC

Rollend L, Fish D, Childs JE. Transovarial transmission of Borrelia spirochetes by Ixodes scapularis: a summary of the literature and recent observations. Ticks Tick-Borne Dis. 2013;4:46–51. doi: 10.1016/j.ttbdis.2012.06.008. PubMed DOI

Rudenko N, Golovchenko M, Kybicova K, Vancova M. Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters. Parasit Vectors. 2019;12:237. doi: 10.1186/s13071-019-3495-7. PubMed DOI PMC

Rudenko N, Golovchenko M, Vancova M, Clark K, Grubhoffer L, Oliver JH. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis. Clin Microbiol infect. 2016;22:267–e9–15. doi: 10.1016/j.cmi.2015.11.009. PubMed DOI

Schröder NWJ, Schombel U, Heine H, Göbel UB, Zähringer U, Schumann RR. Acylated cholesteryl galactoside as a novel immunogenic motif in Borrelia burgdorferi sensu stricto. J Biol Chem. 2003;278:33645–33653. doi: 10.1074/jbc.M305799200. PubMed DOI

Schuijt TJ, Coumou J, Narasimhan S, Dai J, Deponte K, Wouters D, Brouwer M, Oei A, Roelofs JJTH, van Dam AP, van der Poll T, Van’t Veer C, Hovius JW, Fikrig E. A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the Lyme disease agent. Cell Host Microbe. 2011;10:136–146. doi: 10.1016/j.chom.2011.06.010. PubMed DOI PMC

Schwameis M, Kündig T, Huber G, von Bidder L, Meinel L, Weisser R, Aberer E, Härter G, Weinke T, Jelinek T, Fätkenheuer G, Wollina U, Burchard G-D, Aschoff R, Nischik R, Sattler G, Popp G, Lotte W, Wiechert D, Eder G, Maus O, Staubach-Renz P, Gräfe A, Geigenberger V, Naudts I, Sebastian M, Reider N, Weber R, Heckmann M, Reisinger EC, Klein G, Wantzen J, Jilma B. Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial. Lancet Infect Dis. 2017;17:322–329. doi: 10.1016/S1473-3099(16)30529-1. PubMed DOI

Shaffer L. Inner workings: Lyme disease vaccines face familiar challenges, both societal and scientific. Proc Natl Acad Sci U S A. 2019;116:19214–19217. doi: 10.1073/pnas.1913923116. PubMed DOI PMC

Shapiro ED, Wormser GP. Prophylaxis with topical azithromycin against Lyme borreliosis. Lancet Infect Dis. 2017;17:246–248. doi: 10.1016/S1473-3099(16)30551-5. PubMed DOI

Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Antimicrob Agents Chemother. 2015;59:4616–4624. doi: 10.1128/AAC.00864-15. PubMed DOI PMC

Shi J, Hu Z, Deng F, Shen S. Tick-borne viruses. Virol Sin. 2018;33:21–43. doi: 10.1007/s12250-018-0019-0. PubMed DOI PMC

Slunge D, Boman A. Learning to live with ticks? The role of exposure and risk perceptions in protective behaviour against tick-borne diseases. PLoS One. 2018;13:6. doi: 10.1371/journal.pone.0198286. PubMed DOI PMC

Smith R, Takkinen J. Lyme borreliosis: Europe-wide coordinated surveillance and action needed? Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull. 2006;11:E060622.1. PubMed

Sprong H, Trentelman J, Seemann I, Grubhoffer L, Rego RO, Hajdušek O, Kopáček P, Šíma R, Nijhof AM, Anguita J, Winter P, Rotter B, Havlíková S, Klempa B, Schetters TP, Hovius JW. ANTIDotE: anti-tick vaccines to prevent tick-borne diseases in Europe. Parasit Vectors. 2014;7:77. doi: 10.1186/1756-3305-7-77. PubMed DOI PMC

Stanek G, Strle F. Lyme borreliosis-from tick bite to diagnosis and treatment. FEMS Microbiol Rev. 2018;42:233–258. doi: 10.1093/femsre/fux047. PubMed DOI

Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet Lond Engl. 2012;379:461–473. doi: 10.1016/S0140-6736(11)60103-7. PubMed DOI

Steere AC. Lyme disease. N Engl J Med. 2001;345:115–125. doi: 10.1056/NEJM200107123450207. PubMed DOI

Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, Steele FM. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum. 1977;20:7–17. doi: 10.1002/art.1780200102. PubMed DOI

Stricker RB, Middelveen MJ. Better drugs for Lyme disease: focus on the spirochete. Infect Drug Resist. 2018;11:1437–1439. doi: 10.2147/IDR.S176831. PubMed DOI PMC

Strnad M, Elsterová J, Schrenková J, Vancová M, Rego ROM, Grubhoffer L, Nebesářová J. Correlative cryo-fluorescence and cryo-scanning electron microscopy as a straightforward tool to study host-pathogen interactions. Sci Rep. 2015;5:18029. doi: 10.1038/srep18029. PubMed DOI PMC

Strnad M, Hönig V, Růžek D, Grubhoffer L, Rego ROM. Europe-wide meta-analysis of Borrelia burgdorferi sensu lato prevalence in questing Ixodes ricinus ticks. Appl Environ Microbiol. 2017;83:15. doi: 10.1128/AEM.00609-17. PubMed DOI PMC

Stübs G, Fingerle V, Wilske B, Göbel UB, Zähringer U, Schumann RR, Schröder NWJ. Acylated cholesteryl galactosides are specific antigens of borrelia causing Lyme disease and frequently induce antibodies in late stages of disease. J Biol Chem. 2009;284:13326–13334. doi: 10.1074/jbc.M809575200. PubMed DOI PMC

E. Tabor Ala. Ticks and Tick-Borne Pathogens. 2019. The Enigma of Identifying New Cattle Tick Vaccine Antigens.

Tanner T, Marks R. Delivering drugs by the transdermal route: review and comment. Skin Res Technol Off J Int Soc Bioeng Skin ISBS Int Soc Digit Imaging Skin ISDIS Int Soc Skin Imaging ISSI. 2008;14:249–260. doi: 10.1111/j.1600-0846.2008.00316.x. PubMed DOI

Tappe J, Jordan D, Janecek E, Fingerle V, Strube C. Revisited: Borrelia burgdorferi sensu lato infections in hard ticks (Ixodes ricinus) in the city of Hanover (Germany) Parasit Vectors. 2014;7:441. doi: 10.1186/1756-3305-7-441. PubMed DOI PMC

Timmaraju VA, Theophilus PAS, Balasubramanian K, Shakih S, Luecke DF, Sapi E. Biofilm formation by Borrelia burgdorferi sensu lato. FEMS Microbiol Lett. 2015;362:fnv120. doi: 10.1093/femsle/fnv120. PubMed DOI

van Duijvendijk G, Coipan C, Wagemakers A, Fonville M, Ersöz J, Oei A, Földvári G, Hovius J, Takken W, Sprong H. Larvae of Ixodes ricinus transmit Borrelia afzelii and B. miyamotoi to vertebrate hosts. Parasit Vectors. 2016;9:97. doi: 10.1186/s13071-016-1389-5. PubMed DOI PMC

Vancová M, Rudenko N, Vaněček J, Golovchenko M, Strnad M, Rego ROM, Tichá L, Grubhoffer L, Nebesářová J. Pleomorphism and viability of the Lyme disease pathogen Borrelia burgdorferi exposed to physiological stress conditions: a correlative cryo-fluorescence and cryo-scanning electron microscopy study. Front Microbiol. 2017;8:596. doi: 10.3389/fmicb.2017.00596. PubMed DOI PMC

Vechtova P, Sterbova J, Sterba J, Vancova M, Rego ROM, Selinger M, Strnad M, Golovchenko M, Rudenko N, Grubhoffer L. A bite so sweet: the glycobiology interface of tick-host-pathogen interactions. Parasit Vectors. 2018;11:594. doi: 10.1186/s13071-018-3062-7. PubMed DOI PMC

Wagemakers Alex, Coumou Jeroen, Schuijt Tim J., Oei Anneke, Nijhof Ard M., van ‘t Veer Cornelis, van der Poll Tom, Bins Adriaan D., Hovius Joppe W.R. An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement. Vector-Borne and Zoonotic Diseases. 2016;16(4):223–228. doi: 10.1089/vbz.2015.1901. PubMed DOI

Walker AR. Ticks and associated diseases: a retrospective review. Med Vet Entomol. 2014;28(Suppl 1):1–5. doi: 10.1111/mve.12031. PubMed DOI

Wallich R, Siebers A, Jahraus O, Brenner C, Stehle T, Simon MM. DNA vaccines expressing a fusion product of outer surface proteins a and C from Borrelia burgdorferi induce protective antibodies suitable for prophylaxis but not for resolution of Lyme disease. Infect Immun. 2001;69:2130–2136. doi: 10.1128/IAI.69.4.2130-2136.2001. PubMed DOI PMC

Wang D, Bayliss S, Meads C. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses. Health Technol assess winch Engl. 2011;15:iii–iv–i1–124. doi: 10.3310/hta15050. PubMed DOI PMC

Wang Y, Kern A, Boatright NK, Schiller ZA, Sadowski A, Ejemel M, Souders CA, Reimann KA, Hu L, Thomas WD, Klempner MS. Pre-exposure prophylaxis with OspA-specific human monoclonal antibodies protects mice against tick transmission of Lyme disease spirochetes. J Infect Dis. 2016;214:205–211. doi: 10.1093/infdis/jiw151. PubMed DOI PMC

Warshafsky S, Lee DH, Francois LK, Nowakowski J, Nadelman RB, Wormser GP. Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis. J Antimicrob Chemother. 2010;65:1137–1144. doi: 10.1093/jac/dkq097. PubMed DOI

Wilske B, Preac-Mursic V, Göbel UB, Graf B, Jauris S, Soutschek E, Schwab E, Zumstein G. An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis. J Clin Microbiol. 1993;31:340–350. doi: 10.1128/JCM.31.2.340-350.1993. PubMed DOI PMC

Wormser GP, Shapiro ED, Strle F. Studies that report unexpected positive blood cultures for Lyme Borrelia-- are they valid? Diagn Microbiol Infect Dis. 2017;89:178–181. doi: 10.1016/j.diagmicrobio.2017.07.009. PubMed DOI PMC

Wressnigg N, Pöllabauer E-M, Aichinger G, Portsmouth D, Löw-Baselli A, Fritsch S, Livey I, Crowe BA, Schwendinger M, Brühl P, Pilz A, Dvorak T, Singer J, Firth C, Luft B, Schmitt B, Zeitlinger M, Müller M, Kollaritsch H, Paulke-Korinek M, Esen M, Kremsner PG, Ehrlich HJ, Barrett PN. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial. Lancet Infect Dis. 2013;13:680–689. doi: 10.1016/S1473-3099(13)70110-5. PubMed DOI

Zhong W, Gern L, Stehle T, Museteanu C, Kramer M, Wallich R, Simon MM. Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC. Eur J Immunol. 1999;29:946–957. doi: 10.1002/(SICI)1521-4141(199903)29:03<946::AID-IMMU946>3.0.CO;2-P. PubMed DOI

Zingg S, Dolle P, Voordouw MJ, Kern M. The negative effect of wood ant presence on tick abundance. Parasit Vectors. 2018;11:164. doi: 10.1186/s13071-018-2712-0. PubMed DOI PMC

Newest 20 citations...

See more in
Medvik | PubMed

Pathogenicity and virulence of Borrelia burgdorferi

. 2023 Dec ; 14 (1) : 2265015. [epub] 20231009

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...