ライフサイエンスコーパス: OspA

1 OspA also binds to itself, suggesting that spirochete-sp

2 OspA and OspB were not detected after day 5.

3 OspA and OspB were not found in the tissues of SCID mice

4 OspA has two globular domains that are connected via a u

5 OspA is produced as borreliae enter the tick vector and

6 OspA is required for normal tick colonization and has be

7 OspA is the major outer surface protein expressed in cul

8 OspA is up-regulated when the organism is in its tick ho

9 OspA vaccination of children aged 2 to 5 years was shown

10 OspA, OspB and OspC are the major outer surface proteins

11 OspA, which is a receptor for attaching spirochetes to t

12 OspA-mediated attachment in the tick provides a possible

13 OspA-vaccine recipients who acquired Lyme disease had si

14 rthritis resolution, but antisera to P37-42, OspA, GT, or six overlapping Arp peptide fragments did n

15 Outer surface lipoprotein A (OspA) and OspB both coimmunoprecipitate with P66, demons

16 lia burgdorferi outer surface lipoprotein A (OspA) was fused to calmodulin (CaM), a conserved eukaryo

17 orrelia burgdorferi outer surface protein A (OspA(161-175)) and with HLA-DR molecules that bind this

18 urgdorferi-specific outer surface protein A (OspA) (antibodies H5332 and H3TS) and B. burgdorferi-spe

19 ding B. burgdorferi outer surface protein A (OspA) and OspC.

20 d for repression of outer surface protein A (OspA) and OspD in the mammal.

21 f two lipoproteins [outer surface protein A (OspA) and outer surface protein C (OspC)] during transmi

22 rgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed

23 mic (PSAM) from the outer surface protein A (OspA) can form highly stable but soluble beta-rich self-

24 Outer surface protein A (OspA) coats the spirochetes from the time they enter tic

25 Borrelia outer surface protein A (OspA) contains a unique single-layer beta-sheet that con

26 Outer surface protein A (OspA) from Borrelia burgdorferi contains a three-strande

27 Outer surface protein A (OspA) from the Lyme disease spirochete Borrelia burgdorf

28 orrelia burgdorferi outer surface protein A (OspA) instead of its coat protein.

29 Outer surface protein A (OspA) is a borrelial protein important in colonization o

30 Outer surface protein A (OspA) is a major lipoprotein of the Borrelia burgdorferi

31 ccine consisting of outer surface protein A (OspA) is commercially available for vaccination of human

32 Outer surface (lipo)protein A (OspA) of Bb has been the most intensively studied of all

33 ctivity between the outer surface protein A (OspA) of Borellia burgdorferi and human leukocyte functi

34 tibody responses to outer surface protein A (OspA) of Borrelia burgdorferi may occur during periods o

35 Outer surface protein A (OspA) of the Lyme disease spirochete is primarily produc

36 ell response to BB: outer surface protein A (OspA) often develops during prolonged episodes of arthri

37 mmunization with Bb outer surface protein A (OspA) or infection with live Bb.

38 orrelia burgdorferi outer surface protein A (OspA) vaccine induces antibodies that prevent transmissi

39 The Lyme disease outer surface protein A (OspA) vaccine is a transmission-blocking vaccine that ta

40 antibodies against outer surface protein A (OspA) were shown to correlate with protection from infec

41 d thermodynamics of outer surface protein A (OspA), a key protein in the life-cycle of Borrelia burgd

42 were obtained using outer surface protein A (OspA), a naturally occurring triacylated lipoprotein ago

43 the tick, including outer surface protein A (OspA), Borrelia iron and copper-binding protein A (BicA)

44 or surface protein, outer surface protein A (OspA), can induce arthritis.

45 croscopy to express outer surface protein A (OspA), compared to only 5% of salivary gland spirochetes

46 a protein (P37-42), outer surface protein A (OspA), or glutathione S-transferase (GT) and then challe

47 d primarily against outer surface protein A (OspA), was readily produced by lymph node cells obtained

48 ase, down-regulates outer surface protein A (OspA), which is abundantly expressed in ticks, during in

49 ia burgdorferi (Bb) outer surface protein A (OspA).

50 eri and recombinant outer surface protein A (OspA).

51 segment of Borrelia outer surface protein A (OspA).

52 and another within outer surface protein A (OspA, beta-sheet) to have high sequence identity (80 and

53 evels of oxygen in the medium did not affect OspA production.

54 After OspA immunization, mice genetically deficient in either

55 ecrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression o

56 )) produced low titers of antibodies against OspA.

57 lop substantial titers of antibodies against OspA.

58 human monoclonal antibodies (HuMabs) against OspA.

59 arthritis develop an immune response against OspA, whereas those with acute Lyme disease usually do n

60 Although OspA(165-184) stimulated nearly all OspA-specific human T cell clones tested to proliferate

61 Although OspA is not a major antigen produced in the mammal, the

62 Although OspA(165-184) stimulated nearly all OspA-specific human

63 In this study, we created an OspA/B-deficient mutant of an infectious human isolate o

64 ue primarily to the inability to generate an OspA/B-deficient mutant from a virulent strain of Bb.

65 tion structure, dynamics and stability of an OspA fragment corresponding to beta-strands 1-12 (termed

66 lagellin antibody, but did not react with an OspA antibody specific to B. burgdorferi, by indirect fl

67 Here we describe studies with an OspA monoclonal antibody (C3.78) to understand the mecha

68 ulations comprised of naturally infected and OspA-vaccinated individuals (P < 0.05).

69 Spirochetes were harvested 2 days later, and OspA expression was assessed at the protein and transcri

70 ch involved stabilizing the modified MBP and OspA subdomains via external interactions with neighbori

71 ciated major outer surface proteins OspC and OspA in Borrelia burgdorferi, the Lyme disease spirochet

72 d to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 cu

73 LR2 or TLR6 inhibit the responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC, supporti

74 and TLR6 in the cellular response to STF and OspA-L in addition to S. epidermidis (PSM) Ags, and that

75 Anti-OspA borreliacidal antibody was detected in supernatants

76 All anti-OspA monoclonal antibodies that block Borrelia transmiss

77 rferi growth-inhibition assay (GIA) and anti-OspA ELISA to assess the antibody responses of vaccine r

78 Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma

79 In contrast, anti-OspA Ab production required the presence of alphabeta T

80 DR11-Tg mice developed higher titers of anti-OspA and anti-Bb antibodies, respectively, than did DR4-

81 d with this mutant developed a specific anti-OspA immune response, and the spirochetes were unable to

82 ly or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from liv

83 cannot be predicted by measuring total anti-OspA antibody.

84 t how TLR2 receptor complex ligands, such as OspA, are handled by the cell once delivered.

85 not recognize tick-specific proteins such as OspA.

86 cture suggests that the natural variation at OspA sequence position 208 in the first loop is a major

87 ermore, cross-reaction between the bacterial OspA and human LFA-1alpha(L) at the T cell level and the

88 Because OspA is normally downregulated when spirochetes moved fr

89 point mutations and deletions did not block OspA secretion, but rather restored one of the otherwise

90 he single-layer beta-sheet (SLB) in Borrelia OspA.

91 e single-layer beta-sheet region of Borrelia OspA protein.

92 The HLA-DRB1*0401 molecule bound both OspA(163-175) and hLFA-1alpha(L330-342) well.

93 ly important B. burgdorferi antigens in both OspA-vaccinated and nonvaccinated individuals.

94 e heterogeneous; many bacteria produced both OspA and OspC, whereas others produced only a single Osp

95 The DRB1*0101 molecule bound OspA(163-175) well, but hLFA-1alpha(L330-342) only weakl

96 folding intermediate of Borrelia burgdorferi OspA into two conformationally distinct species and dete

97 strategy, we dissected Borrelia burgdorferi OspA, a predominantly beta-sheet protein containing a un

98 d virulence factors of Borrelia burgdorferi, OspA and OspC, are not fully understood.

99 ified lipoprotein from Borrelia burgdorferi, OspA.

100 rendered the cells susceptible to killing by OspA-specific antiserum.

101 preferential gamma interferon production by OspA-specific CD4(+) T cells.

102 resulted in OspA seroconversion, confirming OspA expression in the host.

103 to outer membrane proteins, including DbpA, OspA, and OspC, suggests that the remarkable protection

104 significant changes in the levels of either OspA or P66.

105 icto 50772, which lacks the plasmid encoding OspA and OspB, or a full-length recombinant OspC protein

106 Flow cytometry was also utilized to evaluate OspA protein expression on individual spirochetes.

107 This decoration of the cells with exogenous OspA did not affect cell's viability.

108 When the ospC mutant was modified to express OspA under control of the ospC regulatory elements, it r

109 r to feeding spirochetes in nymphs expressed OspA but not OspC.

110 er, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became

111 amounts of these antigens were negative for OspA and OspC.

112 OPN was not required for OspA-induced cytokine production; however, macrophages f

113 , as well as cloned human cells specific for OspA(165-184), the immunodominant epitope, from five DRB

114 the importance of the antigen stability for OspA's vaccine efficacy.

115 ecific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein Osp

116 T cells from OspA-immunized and Bb-infected DR11-Tg mice had defectiv

117 OspC is very different from OspA and similar to the extracellular domain of the bact

118 FTK-OspA did not stimulate human or mouse DR4-restricted, WT

119 ation trials, as both C3H/HeJ and BALB/c FTK-OspA-vaccinated mice were protected from Bb infection.

120 how here that the protective efficacy of FTK-OspA is indistinguishable from that of WT-OspA in vaccin

121 We generated a form of rOspA, FTK-OspA, in which the LFA-1alpha(L)/rOspA crossreactive T c

122 th concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean

123 However, OspA/B function was essential for Bb colonization of and

124 Although differences in OspA mRNA levels were observed between cultured and tick

125 ults provide a rationale for improvements in OspA-based vaccines and suggest possible designs for mor

126 Our analysis of 15N relaxation parameters in OspA shows that the putative-binding region contains and

127 H mice to infected C3H-scid mice resulted in OspA seroconversion, confirming OspA expression in the h

128 veral B. burgdorferi lipoproteins, including OspA and VlsE, could substitute for OspC at the initial

129 (Pam(3)Cys)-modified lipoproteins, including OspA from the Lyme disease spirochete Borrelia burgdorfe

130 matory in vivo environment show an increased OspA expression relative to B. burgdorferi kept under no

131 kin tissue of SCID mice; moreover, increased OspA, OspE or VlsE expression allowed the mutant to caus

132 l-length wild-type (wt) OspA or to an intact OspA N-terminal "tether" peptide retained their competen

133 patients had at least one of the seven known OspA peptide-binding DR molecules compared with 46% of t

134 ted) or lipidated outer surface protein A (L-OspA) augmented their SOCS1/SOCS3 mRNA and protein expre

135 HBb, LPS, and L-OspA yielded similar kinetics of cytokine production.

136 cell line and recombinant lipidated OspA (L-OspA) as the model target cell and stimulant, respective

137 e and purified recombinant lipidated OspA (L-OspA) were used as the model target cell and stimulant,

138 on of IL-10 by THP-1 cells stimulated with L-OspA was autoregulated by a negative feedback mechanism

139 1 and its avirulent derivative B313 (lacking OspA and DbpA) conferred highly significant protection a

140 Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is deriv

141 ly derivatized forms of both the full length OspA lipoprotein delivered as a recombinant soluble CD14

142 s significantly smaller than the full-length OspA, and thus it is expected to facilitate studies of t

143 ficantly reduced with respect to full-length OspA.

144 than the corresponding region in full-length OspA.

145 onocytic cell line and recombinant lipidated OspA (L-OspA) as the model target cell and stimulant, re

146 cell line and purified recombinant lipidated OspA (L-OspA) were used as the model target cell and sti

147 thin the tether of major surface lipoprotein OspA results in its inefficient translocation across the

148 ia burgdorferi monomeric surface lipoprotein OspA was dependent on residues in the N-terminal "tether

149 imeras between the outer surface lipoprotein OspA, the periplasmic oligopeptide-binding lipoprotein O

150 ed by sonicated bacteria, by the lipoprotein OspA, and by factors released into the BSKII medium duri

151 dorferi outer surface protein A lipoprotein (OspA-L).

152 e is based on the outer-surface lipoprotein (OspA) of the pathogen Borrelia burgdorferi, and 95% of v

153 er peptides of Borrelia surface lipoproteins OspA and Vsp1.

154 g among the major outer surface lipoproteins OspA, OspC, and VlsE at different stages of the infectio

155 e four randomly chosen surface lipoproteins, OspA, OspE, VlsE or DbpA, fully protected the ospC mutan

156 more, host-adapted B. burgdorferi with a low OspA phenotype upregulates OspA expression when transfer

157 immunizations than did age- and sex-matched OspA recipients without Lyme disease.

158 n which CaM was fused to truncated or mutant OspA N-terminal tether peptides were targeted to the per

159 (iv) Like native OspA, the recombinant OspA decorating the cells was acce

160 to the mammalian host expresses little or no OspA.

161 <.001) and was observed in 18 (78%) of 23 of OspA-responsive subjects.

162 , host complement did enhance the ability of OspA antibody to block larvae from acquiring spirochetes

163 To further understand the consequences of OspA production in the host, we created a Borrelia burgd

164 population in the gut, a subset depleted of OspA entered the salivary glands and stably infected the

165 mbinant chimeric borrelia proteins devoid of OspA (rNon-OspA) that can be used to detect antibodies t

166 art, by residues in the C-terminal domain of OspA that are largely inaccessible to solvent in all X-r

167 ce-exposed loops of the C-terminal domain of OspA that are on the tip of the elongated molecule most

168 ational epitopes in the C-terminal domain of OspA, suggesting the possibility of using the C-terminal

169 Rrp2-RpoN-RpoS pathway and downregulation of OspA form a positive feedback loop that allows spirochae

170 , which is involved in the downregulation of OspA when B. burgdorferi is grown in a mammalian host-ad

171 Thus, the effects of OspA antibody on nymphal transmission and larval acquisi

172 Here we report the engineering of OspA variants that contain larger single-layer beta-shee

173 es an important protective B-cell epitope of OspA against which protective sera have strong levels of

174 pologically analogous to the LA-2 epitope of OspA and is centered around OspB Lys-253, a residue esse

175 The immunodominant epitope of OspA in the context of HLA-DRB1*0401 corresponds to amin

176 We have now mapped the LA-2 epitope of OspA using both NMR chemical-shift perturbation measurem

177 d T cell crossreactivity between epitopes of OspA and lymphocyte function-associated antigen 1alpha(L

178 evealed that the heterogeneous expression of OspA and OspC displayed by spirochete populations during

179 by feeding ticks and decreased expression of OspA in B. burgdorferi recovered from ticks that fed on

180 orferi and result in increased expression of OspA.

181 tether feature leads to premature folding of OspA in the periplasm and thereby prevents secretion thr

182 Both forms of OspA are internalized in a similar manner to acetylated

183 We prepared a C-terminal fragment of OspA by removing approximately 45% of residues from the

184 otic-refractory arthritis had frequencies of OspA(161-175)-specific CD4(+) T cells in peripheral bloo

185 l samples were available, the frequencies of OspA(161-175)-specific T cells declined to low or undete

186 mer reagents to determine the frequencies of OspA(161-175)-specific T cells in samples of PBMC and sy

187 itis initially have increased frequencies of OspA(161-175)-specific T cells.

188 However, the precise function of OspA (along with that of its close relative and operonic

189 To further study the importance of OspA during tick colonization, we constructed a form of

190 Inhibition of internalization of OspA via treatment with cytochalasin D or of the lipohex

191 There were no changes in the levels of OspA, NapA, P66, and three other OppA orthologs.

192 ross-linking of bacteria or cross-linking of OspA molecules was not required for protection because C

193 of mRFP1 to short N-terminal lipopeptides of OspA, and surprisingly OppAIV, were targeted to the spir

194 Localization of OspA and OppAIV point mutants showed that Borrelia lipop

195 We observe co-localization of OspA with lysosomes but not with the Golgi complex.

196 The magnitude of OspA(163-175) binding correlated well with the frequenci

197 The parallel occurrence of OspA antibodies and arthritic episodes suggests that Osp

198 and a strain that produces OspB in place of OspA within ticks.

199 ospA, our findings suggest that reduction of OspA can also activate this pathway.

200 To elucidate the role of OspA in the vector, we created an insertional deletion o

201 en speculated about the potential role(s) of OspA in the life cycle of Bb.

202 This is in contrast to the structure of OspA, a major surface protein mainly present when spiroc

203 and then challenged by syringe or tick, only OspA conferred protection.

204 Assays with LFA- or OspA-DR4 monomers revealed that higher concentrations of

205 evels of either the synthetic lipopeptide or OspA lipoprotein agonist.

206 B. burgdorferi proteins, including the OspC, OspA, and Erp proteins, indicated that each protein is r

207 ression of the outer surface proteins (Osps) OspA and OspC by use of quantitative Western blotting.

208 ic test would be useful independent of prior OspA vaccination status.

209 B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and ma

210 homogeneous population that mainly produced OspA only.

211 We conclude that spirochetes producing OspA and B from the flaB promoter in immunocompetent mic

212 Although the spirochetal protein OspA is capable of stimulating immune cells in a CD14- a

213 egy by using Borrelia outer surface protein (OspA) whose single-layer beta-sheet located between two

214 OspC and the outer membrane proteins OspA and OspB were prominent at the earliest time point,

215 els of B. burgdorferi outer surface proteins OspA and OspC were measured, OspC protein and mRNA level

216 P-Lys(B30) as adjuvant, are shown to provoke OspA-specific antibody responses with a strong Th1-bias

217 Antigens included recombinant OspA and OspC (all strain B31) and human LFA-1 peptide (

218 i in aluminum hydroxide, but not recombinant OspA.

219 ed with 30, 60, or 120 microg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B

220 A Lyme disease vaccine based on recombinant OspA has been approved for human use.

221 (i) Purified recombinant OspA or OspD lipoproteins associated with Borrelia burgd

222 (iv) Like native OspA, the recombinant OspA decorating the cells was accessible to antibodies a

223 ve been rendered obsolete by the recombinant OspA Lyme disease vaccine.

224 individuals vaccinated with the recombinant OspA vaccine had an antibody response to the C6 peptide.

225 rategy should be useful for further refining OspA-based vaccines and developing recombinant vaccines

226 feri mutant that was unable to down regulate OspA.

227 tting, stationary-phase spirochetes released OspA, OspB, and flagellin.

228 apularis ticks, and many spirochetes repress OspA production during the feeding process.

229 Thus, B. burgdorferi-derived RNA, OspA, and non-nucleic acid ligands present in both sonic

230 meric borrelia proteins devoid of OspA (rNon-OspA) that can be used to detect antibodies to diagnosti

231 ata demonstrate that this new sensitive rNon-OspA ELISA can be used for the laboratory detection of B

232 However, the rNon-OspA assay can differentiate between populations compris

233 The rNon-OspA assay is as sensitive and specific as the whole-cel

234 The rNon-OspA test was compared with two commercially available w

235 s associated with false-positive serologies, OspA-vaccinated individuals, and healthy high-risk worke

236 Upon serum starvation, OspA shows some localization to the Golgi apparatus wher

237 ed the signaling pathway in response to STF, OspA-L, and PSM in TLR2-transfected HMEC.

238 t corresponding to beta-strands 1-12 (termed OspA[27-163]), which lacks a majority of the C-terminal

239 We conclude that OspA serves a critical antibody-shielding role during ve

240 It has recently been demonstrated that OspA specifically binds to the gut of the intermediate t

241 ger available, in part because of fears that OspA causes arthritis in people.

242 an isolate of Bb (strain 297) and found that OspA/B function was not required for either Bb infection

243 ese correlations support the hypothesis that OspA(163-175) is the critical epitope in triggering anti

244 orferi CONCLUSIONS: Our study indicates that OspA-specific HuMabs can prevent the transmission of Bor

245 and extend previous studies indicating that OspA both protects spirochetes within ticks from mammali

246 hat do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, whi

247 bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin.

248 We propose that OspA antibody binding to the surface of spirochetes bloc

249 Here we show that OspA mediates spirochete attachment to the tick gut by b

250 user effect (NOE) connectivities showed that OspA[27-163] is folded except the 12th and final beta-st

251 Furthermore, they suggest that OspA emerges tail-first on the bacterial surface, yet in

252 he salivary gland, our findings suggest that OspA-expressing midgut spirochetes may be particularly s

253 ibodies and arthritic episodes suggests that OspA expression is upregulated during infection with B.

254 This preferential expression suggests that OspA may have an important function in the vector.

255 The OspA single-layer beta-sheet achieves efficient hydropho

256 ld function as the adjuvant receptor for the OspA vaccine.

257 The removal of ineffective parts from the OspA antigen may reduce side effects and lead to a safer

258 ence in the beta-hairpin conformation in the OspA protein provide a tractable experimental system for

259 that may be responsible for maintaining the OspA-negative state of spirochetes during infection.

260 tures describing the energy landscape of the OspA backbone are derived from the temperature dependenc

261 Mutagenesis of the OspA N-terminus defined less than five N-terminal amino

262 me disease in patients who have received the OspA vaccine.

263 s were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1-0.8]).

264 Surprisingly, however, antibodies to OspA and BicA have been noted in American patients with

265 immune responses were found as frequently to OspA as to OspC and FlaB.

266 may account for human hyporesponsiveness to OspA vaccination.

267 to outer surface protein (Osp) C, but not to OspA.

268 -) mice responded normally to PGN but not to OspA.

269 Proliferation to OspA was detected in 11 (28%) of 39 of subjects presenti

270 Reactivity to OspA and LFA-1 was significantly correlated (P<.001) and

271 3-loaded HLA-DRB1*0401 tetramers, respond to OspA and hLFA1alpha with a different cytokine profile, s

272 To analyze the nature of response to OspA and LFA-1alpha(L), we used OspA-specific T cell hyb

273 mportance of TLR2 in the humoral response to OspA was confirmed, because overall levels of immunoglob

274 T cell response to OspA was similar between cases and vaccine controls, as

275 disease vaccination, and immune responses to OspA were not significantly more common in arthritis cas

276 arthritis commonly had antibody responses to OspA, BicA, and OspD.

277 ges from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responde

278 Nearly 100 unique OspA-specific HuMabs were generated, and 4 HuMabs (221-7

279 Unlipidated OspA was not immunogenic in wild-type or TLR2-deficient

280 sion under these conditions, but unlipidated OspA was ineffective.

281 orferi with a low OspA phenotype upregulates OspA expression when transferred to an inflammatory in v

282 response to OspA and LFA-1alpha(L), we used OspA-specific T cell hybrids from DR4 transgenic mice, a

283 tope, from five DRB1*0401(+) patients, using OspA-MHC class II tetramers.

284 entify inflammation as a mediator of in vivo OspA expression in host-adapted B. burgdorferi, providin

285 ting for internalization with OspA even when OspA is delivered as a rsCD14 complex.

286 P66, demonstrating that P66 associates with OspA and OspB in B. burgdorferi.

287 not humoral reactivity was often found with OspA.

288 of viable B. burgdorferi and B. hermsii with OspA rendered the cells susceptible to killing by OspA-s

289 orferi and found significant homologies with OspA protein.

290 In experiments with mice hyperimmunized with OspA, complement was not required to kill spirochetes wi

291 man immunoglobulin genes were immunized with OspA from B. burgdorferi to generate human monoclonal an

292 apable of competing for internalization with OspA even when OspA is delivered as a rsCD14 complex.

293 tients had marginal antibody reactivity with OspA.

294 ra obtained from individuals vaccinated with OspA.

295 Vaccination with OspA generates an immune response that can prevent bacte

296 CaM was fused to full-length wild-type (wt) OspA or to an intact OspA N-terminal "tether" peptide re

297 stimulate antibody responses specific for WT-OspA that were similar to mice vaccinated WT-OspA.

298 TK-OspA is indistinguishable from that of WT-OspA in vaccination trials, as both C3H/HeJ and BALB/c F

299 stimulate human or mouse DR4-restricted, WT-OspA-specific T cells, whereas it did stimulate antibody

300 OspA that were similar to mice vaccinated WT-OspA.