Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease. It is a zoonotic, vector-borne disease transmitted by ticks and is named after the researcher Willy Burgdorfer who first isolated the bacterium in 1982. B. burgdorferi is one of the few pathogenic bacteria that can survive without iron, having replaced all of its iron-sulfur cluster enzymes with enzymes that use manganese, thus avoiding the problem many pathogenic bacteria face in acquiring iron (Wiki: B. burgdorferi).
4. Microbial Pathogenesis
B. burgdorferi is deposited in skin lesions left by Ixodes ticks, and can then invade the bloodstream leading to dissemination throughout the body and cause problems in joints and nervous tissues (Salyers and Whitt., 2002).
5. Host Ranges and Animal Models
White footed mouse are the reservoir of B. burgdorferi. The bacteria are carried by ticks which vector the bacteria to other hosts such as humans, as well as small mammals such as voles and shrews. Animal models include rabbits, mice and dogs (Salyers and Whitt., 2002).
6. Host Protective Immunity
In most people B. burgdorferi is cleared from the bloodstream via antibodies and phagocytic cells (Salyers and Whitt., 2002).
>YP_003110629.1 decorin binding protein A (plasmid) [Borreliella burgdorferi 297]
MIKCNNKTFNNLLKLTILVNLLISCGLTGATKIKLESSAKAIVDEIDAIKKKAASMGVNFDAFKDKKTGS
GVSENPFILEAKVRATTVAEKFVIAIEEEATKLKETGSSGEFSAMYDLMFEVSKPLQELGIQEMTKTVSM
AAEENPPTTAQGVLEIAKKMREKLQRVHKKNQDTLKKKNTEDSTAKS
Molecule Role :
Protective antigen
Molecule Role Annotation :
Mice immunized with recombinant DbpA protein are protected against challenge with Borrelia burgdorferi (Hanson et al., 2000).
Molecule Role Annotation :
A flagella-less mutant of Borrelia burgdorferi (HB19Fla-) was attenuated in immunodeficient SCID mice. Mice were challenged 28 days later with virulent strain Sh. 2 and were protected from challenge (Sadziene et al., 1996).
>NP_045688.1 outer surface protein A (plasmid) [Borreliella burgdorferi B31]
MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGEMKVLVSKEKNKDGKYDLIATVDKLELKGTSDKN
NGSGVLEGVKADKSKVKLTISDDLGQTTLEVFKEDGKTLVSKKVTSKDKSSTEEKFNEKGEVSEKIITRA
DGTRLEYTGIKSDGSGKAKEVLKGYVLEGTLTAEKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAAT
KKTAAWNSGTSTLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEITKLDEIKNALK
Molecule Role :
Protective antigen
Molecule Role Annotation :
Mice immunized with recombinant OspA protein were protected from challenge with Borrelia burgdorferi (Probert and LeFebvre, 1994).
>NP_045689.2 outer surface protein B (plasmid) [Borreliella burgdorferi B31]
MRLLIGFALALALIGCAQKGAESIGSQKENDLNLEDSSKKSHQNAKQDLPAVTEDSVSLFNGNKIFVSKE
KNSSGKYDLRATIDQVELKGTSDKNNGSGTLEGSKPDKSKVKLTVSADLNTVTLEAFDASNQKISSKVTK
KQGSITEETLKANKLDSKKLTRSNGTTLEYSQITDADNATKAVETLKNSIKLEGSLVGGKTTVEIKEGTV
TLKREIEKDGKVKVFLNDTAGSNKKTGKWEDSTSTLTISADSKKTKDLVFLTDGTITVQQYNTAGTSLEG
SASEIKNLSELKNALK
Molecule Role :
Protective antigen
Molecule Role Annotation :
Mice immunized with recombinant OspB protein were protected from challenge with Borrelia burgdorferi (Probert and LeFebvre, 1994).
>NP_047005.1 outer surface protein C (plasmid) [Borreliella burgdorferi B31]
MKKNTLSAILMTLFLFISCNNSGKDGNTSANSADESVKGPNLTEISKKITDSNAVLLAVKEVEALLSSID
EIAAKAIGKKIHQNNGLDTENNHNGSLLAGAYAISTLIKQKLDGLKNEGLKEKIDAAKKCSETFTNKLKE
KHTDLGKEGVTDADAKEAILKTNGTKTKGAEELGKLFESVEVLSKAAKEMLANSVKELTSPVVAESPKKP
Molecule Role :
Protective antigen
Molecule Role Annotation :
Mice immunized with recombinant OspC protein were protected from challenge with Borrelia burgdorferi (Probert and LeFebvre, 1994).
Vaccination Protocol:
Mice were immunized by intraperitoneal injection of 10 μg of DbpAN40, 10 μg of OspAN40, 5 μg of DbpAN40 plus 5 μg of OspAN40, or 2.5 μg of E. coli protein extract with complete Freund's adjuvant and then, 4 weeks later, were given a second immunization of protein in incomplete Freund's adjuvant (Hanson et al., 2000).
Challenge Protocol:
At week 6, five of the mice in each immunization group were challenged by subcutaneous injection, into the dorsolateral thorax, of cloned B. burgdorferi N40 (Hanson et al., 2000).
Efficacy:
All mice immunized with the combined DbpAN40-OspAN40 vaccine (5 μg of each antigen) were protected against even the highest challenge dose of 10^6 spirochetes (Hanson et al., 2000).
Vaccination Protocol:
Mice were immunized by intraperitoneal injection of 10 μg of DbpAN40, 10 μg of OspAN40, 5 μg of DbpAN40 plus 5 μg of OspAN40, or 2.5 μg of E. coli protein extract with complete Freund's adjuvant and then, 4 weeks later, were given a second immunization of protein in incomplete Freund's adjuvant (Hanson et al., 2000).
Challenge Protocol:
At week 6, five of the mice in each immunization group were challenged by subcutaneous injection, into the dorsolateral thorax, of cloned B. burgdorferi N40 (Hanson et al., 2000).
Efficacy:
Mice immunized with recombinant DbpA protein are protected against challenge with Borrelia burgdorferi. Nearly all mice immunized with 10 μg of DbpAN40 were protected from challenge with 10^3 or 10^4 spirochetes (Hanson et al., 2000).
3. B. burgdorferi DNA vaccine encoding strain B31 OspA
Vaccination Protocol:
Female C3H/HeN mice (6-10 weeks old) were injected with plasmid diluted in sterile 0.9% saline. Each mouse received intramuscular injections into left and right rectus femoris muscles with 50 J-lg of plasmid in 50 J-lL of saline. For immunization with protein, mice were injected in the back with purified B31 rOspA lipoprotein (Luke et al., 1997).
Vaccine Immune Response Type:
VO_0000286
Immune Response:
Sera from mice immunized with the ospA-bearing plasmid DNA had high levels of antibody that recognized both native and rOspA lipoprotein (Luke et al., 1997).
Challenge Protocol:
Mice were challenged intradermally by injecting 100 x ID50 of the infectious isolate at the base of the tail (Luke et al., 1997).
Efficacy:
Immunization with VR2210 protected 100% of mice against infection with Sh-2-82 or N40, 2 infectious strains of B. burgdorferi (Luke et al., 1997).
4. B. burgdorferi DNA vaccine pCMV-ZS7/TPA encoding OspC from Borrelia burgdorferi sensu lato
Immune Response:
Both i.d. injection and gene-gun application of plasmid DNA encoding the ospC gene induced a reliable humoral response with high antibody titers, antigen-specific cellular responses and, most importantly, provided effective protection (Scheiblhofer et al., 2003).
Challenge Protocol:
Control groups received challenge doses B. burgdorferi strain ZS7 of 10^4, 10^3, 10^2, and 10 live spirochetes per animal (Scheiblhofer et al., 2003).
Efficacy:
The protection rate after challenge with 10 B. burgdorferi organisms per mouse was between 80% and 100% for all groups. These results demonstrate that a DNA vaccine encoding OspC of B. burgdorferi is suitable for inducing protection against Lyme borreliosis (Scheiblhofer et al., 2003).
Vaccination Protocol:
Four-week-old female mice were primed intraperitoneally with 20 μg of each immunogen in 200 μL of complete Freund's adjuvant. Three boosts containing the same amount of immunogen in incomplete Freund's adjuvant were administered at 2, 5, and 8 weeks following the initial injection (Probert and LeFebvre, 1994).
Challenge Protocol:
Ten days following the final boost, mice received a subcutaneous inoculation containing 10^7 SON 188 organisms in 100 μl of BSK II medium (Probert and LeFebvre, 1994).
Efficacy:
Mice immunized with recombinant OspA protein were protected from challenge with Borrelia burgdorferi (Probert and LeFebvre, 1994).
Vaccination Protocol:
Four-week-old female mice were primed intraperitoneally with 20 μg of each immunogen in 200 μL of complete Freund's adjuvant. Three boosts containing the same amount of immunogen in incomplete Freund's adjuvant were administered at 2, 5, and 8 weeks following the initial injection (Probert and LeFebvre, 1994).
Challenge Protocol:
Ten days following the final boost, mice received a subcutaneous inoculation containing 107 SON 188 organisms in 100 μl of BSK II medium (Probert and LeFebvre, 1994).
Efficacy:
Mice immunized with recombinant OspB protein were protected from challenge with Borrelia burgdorferi (Probert and LeFebvre, 1994).
Vaccination Protocol:
Four-week-old female mice were primed intraperitoneally with 20 μg of each immunogen in 200 μL of complete Freund's adjuvant. Three boosts containing the same amount of immunogen in incomplete Freund's adjuvant were administered at 2, 5, and 8 weeks following the initial injection (Probert and LeFebvre, 1994).
Challenge Protocol:
Ten days following the final boost, mice received a subcutaneous inoculation containing 107 SON 188 organisms in 100 μl of BSK II medium (Probert and LeFebvre, 1994).
Efficacy:
Mice immunized with recombinant OspC protein were protected from challenge with Borrelia burgdorferi (Hanson et al., 1998).
Live, attenuated vaccine; Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Gray wolf
IV. References
1. Brandt et al., 2014: Brandt KS, Patton TG, Allard AS, Caimano MJ, Radolf JD, Gilmore RD. Evaluation of the Borrelia burgdorferi BBA64 protein as a protective immunogen in mice. Clinical and vaccine immunology : CVI. 2014; 21(4); 526-533. [PubMed: 24501342].
2. Bryksin et al., 2005: Bryksin AV, Godfrey HP, Carbonaro CA, Wormser GP, Aguero-Rosenfeld ME, Cabello FC. Borrelia burgdorferi BmpA, BmpB, and BmpD proteins are expressed in human infection and contribute to P39 immunoblot reactivity in patients with Lyme disease. Clinical and diagnostic laboratory immunology. 2005; 12(8); 935-940. [PubMed: 16085911].
3. Floden et al., 2013: Floden AM, Gonzalez T, Gaultney RA, Brissette CA. Evaluation of RevA, a fibronectin-binding protein of Borrelia burgdorferi, as a potential vaccine candidate for lyme disease. Clinical and vaccine immunology : CVI. 2013; 20(6); 892-899. [PubMed: 23595502].
4. Hanson et al., 1998: 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. Infection and immunity. 1998; 66(5); 2143-2153. [PubMed: 9573101].
5. Hanson et al., 2000: 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. Infection and immunity. 2000; 68(11); 6457-6460. [PubMed: 11035759].
6. Labandeira-Rey et al., 2001: Labandeira-Rey M, Baker EA, Skare JT. VraA (BBI16) protein of Borrelia burgdorferi is a surface-exposed antigen with a repetitive motif that confers partial protection against experimental Lyme borreliosis. Infection and immunity. 2001; 69(3); 1409-1419. [PubMed: 11179306].
7. Probert and LeFebvre, 1994: Probert WS, LeFebvre RB. Protection of C3H/HeN mice from challenge with Borrelia burgdorferi through active immunization with OspA, OspB, or OspC, but not with OspD or the 83-kilodalton antigen. Infection and immunity. 1994; 62(5); 1920-1926. [PubMed: 8168958].
8. Sadziene et al., 1996: Sadziene A, Thompson PA, Barbour AG. A flagella-less mutant of Borrelia burgdorferi as a live attenuated vaccine in the murine model of Lyme disease. The Journal of infectious diseases. 1996; 173(5); 1184-1193. [PubMed: 8627071].
9. Salyers and Whitt., 2002: Abigail A. Salyers, Dixie D. Whitt. The Spirochetes: Borrelia burgdorferi and Treponema pallidum. 187-199. Bacterial Pathogenesis: A Molecular Approach. 2002. ASM Press, Washington D.C. USA.
10. Ulbrandt et al., 2001: Ulbrandt ND, Cassatt DR, Patel NK, Roberts WC, Bachy CM, Fazenbaker CA, Hanson MS. Conformational nature of the Borrelia burgdorferi decorin binding protein A epitopes that elicit protective antibodies. Infection and immunity. 2001; 69(8); 4799-4807. [PubMed: 11447153].
