ライフサイエンスコーパス: VHH

1 VHH heterodimer toxin-neutralizing agents containing two

2 VHH proteins recognizing foot-and-mouth disease virus (F

3 VHH sequences were modified by inclusion of a C-terminal

4 VHH single-domain antibodies have been demonstrated to n

5 is highly divergent from previous anti-HIV-1 VHH and its own germline sequence.

6 Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptos

7 Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to t

8 All 16 VHHs were suitable primary reagents for the detection of

9 For 16 VHHs, the corresponding antigens were identified by affi

10 toxins can be promoted by coadministering a VHH-based toxin-neutralizing agent with an antitag monoc

11 HHs from an immunized alpaca and developed a VHH-based immunoassay using 3-phenoxybenzoic acid (3-PBA

12 extracts and more particularly to generate a VHH phage library against native Arabidopsis thaliana se

13 Here we describe the construction of a VHH phage display library against the cyanobacterial hep

14 port the discovery and characterization of a VHH single domain antibody (nanobody) isolated from a ll

15 In this study, a VHH phagemid library generated from a llama that was mul

16 X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 A resolution.

17 The structure reveals that the Aa1 VHH binds in the alpha-exosite of the BoNT/A Lc, far fro

18 This variable domain of an H chain-only Ab (VHH or nanobody) significantly inhibited both phosphoant

19 Furthermore, several of the anti-albumin VHHs were used successfully for storage protein localisa

20 All VHHs bind the capsid in the canyon at sites that extensi

21 olic expression of NP-specific VHHs (alphaNP-VHHs) disrupts virus replication at an early stage of th

22 Although VHH domains can function in the absence of an interloop

23 glycosylphosphatidylinositol (GPI)-anchored VHH JM2 and JM4 along with an E4 control and transduced

24 ly isolated (here referred to as VHH JM2 and VHH JM4, respectively).

25 Another VHH appears to recognize the LF C-terminal domain and ex

26 ized three single domain camelid antibodies (VHH) against cluster II.

27 e variable domain of heavy-chain antibodies (VHH) were isolated, transcribed to cDNA, and cloned into

28 loying His6-tagged single-domain antibodies (VHH).

29 ents of camelid heavy chain-only antibodies (VHH) conjugated to Pseudomonas exotoxin A to deplete mye

30 ble domains of llama heavy-chain antibodies (VHHs) as capture molecule, and a surface plasmon resonan

31 therapeutic use of single-chain antibodies (VHHs) is limited by their short half-life in the circula

32 two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bin

33 ated a panel of single-VH domain antibodies (VHHs) that recognize distinct epitopes within IpaD.

34 erapeutics such as single-domain antibodies (VHHs).

35 omains of llama heavy chain-only antibodies (VHHs) against ETEC to the Fc part of a porcine immunoglo

36 able domains of heavy-chain-only antibodies (VHHs) are becoming a salient option as immunoassay reage

37 fferent camelid heavy-chain only antibodies (VHHs) joined via peptide linkers have proven to have pot

38 ains of camelid heavy chain-only antibodies (VHHs) with affinity for PA were obtained from immunized

39 Nanobodies (single-domain antibodies, VHH) are the smallest antibody-based fragments possessin

40 chain interface of conventional antibodies, VHHs are not particularly apt to bind small analytes and

41 radiolabeled single-domain variable antibody VHH fragments (Nanobodies).

42 d in a natural camelid heavy-chain antibody (VHH) that binds to ribonuclease A.

43 ble domain of the heavy-chain-only antibody (VHH), are single-domain antigen-binding fragments derive

44 ed from a camelid heavy-chain-only antibody (VHH).

45 ing camelid single-domain antibodyfragments (VHHs) as capture agents.

46 Antiviral VHHs prevented nuclear import of viral ribonucleoprotein

47 We identified 19 antiviral VHHs that protect human A549 cells from lethal infection

48 been recently isolated (here referred to as VHH JM2 and VHH JM4, respectively).

49 ricin-specific VHH heterodimers, as well as VHH homodimers, and characterized them for their ability

50 chips with randomly immobilized biotinylated VHHs were compared to streptavidin-coated SPR chips, on

51 similar quantities of oriented biotinylated VHHs were non-covalently immobilized.

52 chanisms by which these so-called bispecific VHH heterodimers promote toxin neutralization remain poo

53 JKH-C7 and the receptor-blocking VHH class (JIK-B8) were expressed as a heterodimeric VHH

54 re further improved by using the phage borne VHH, IC(50) = 0.1 ng/mL and LOD = 0.01 ng/mL.

55 xposed to elevated temperatures, the camelid VHH antibodies retained more reactivity than a polyclona

56 alternates is demonstrated for three camelid VHH domain-porcine alpha-amylase interactions.

57 in complexes with four 80S-specific camelid VHHs (Nanobodies).

58 thermodynamics for an anti-caffeine camelid (VHH) antibody.

59 gen recognition and, in particular, camelid (VHH) domains.

60 Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity.

61 A (89)Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as

62 y of the variable domain of the heavy chain (VHH).

63 better efficacy than the separate component VHHs.

64 the sole neutralizing anti-RTB VHH to create VHH "heterodimers." As compared with equimolar concentra

65 antibody fragments, such as camelid-derived VHHs, can serve as inhibitors or activators of intracell

66 tion on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K(d)) from

67 We identified 25 distinct VHH families binding trimeric Env, of which 6 neutralize

68 a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from he

69 aller antibody fragments, the single-domain (VHH) version of JM4 neutralized less well than the full-

70 ion of a camelid heavy-chain-only VH domain (VHH)-based neutralizing agent (VNA) targeting Stx1 and S

71 in complex with the antigen binding domains (VHH) of five unique single-chain monoclonal antibodies t

72 agged, heavy chain-only antibody VH domains (VHHs) specific for the ricin enzymatic (RTA) and binding

73 role of an additional hallmark of dromedary VHHs, i.e. the extra disulfide bond between the first an

74 nding surface on the VHHs is unique for each VHH.

75 ed anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the ant

76 r mouse and human red blood cells to express VHHs against botulinum neurotoxin A (BoNT/A) on their su

77 We expressed VHHs from an immunized alpaca and developed a VHH-based

78 e that engineered red blood cells expressing VHHs can provide prolonged prophylactic protection again

79 in vivo antibody maturation process favoring VHH domains with an interloop disulfide bond.

80 All five VHHs bind deep in the virus canyon at similar sites that

81 ound to participate in binding with all five VHHs.

82 Rather, the five VHHs had overlapping structural epitopes on the surface

83 ngly extensive) surface for each of the five VHHs.

84 e peptide (3 kDa) containing the epitope for VHH recognition was tested, much larger effects of captu

85 In this way, four VHH-IgG and four VHH-IgA antibodies were produced to levels of about 3% a

86 In this way, four VHH-IgG and four VHH-IgA antibodies were produced to lev

87 Interestingly, although the four VHHs bind to the same site, the structures of the expand

88 We generated single-domain Ab fragments (VHHs) specific for class II MHC (MHCII), CD11b, and CD36

89 id-derived single-domain antibody fragments (VHHs or nanobodies) offer a possible solution to this ch

90 id-derived single-domain antibody fragments (VHHs) against influenza virus nucleoprotein (NP), a vira

91 PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratum

92 rary of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that binds TgCDPK1

93 looctyne was reacted to azide functionalized VHH domains, using click chemistry.

94 GPI-VHH JM4, but not GPI-VHH JM2, in transduced CD4(+) cell

95 Finally, GPI-VHH JM4-transduced human primary CD4 T cells efficiently

96 Expression of GPI-VHH JM4, but not GPI-VHH E4 and JM2, on the surface of transduced TZM.bl cell

97 GPI-VHH JM4, but not GPI-VHH JM2, in transduced CD4(+) cell lines and human prima

98 Expression of GPI-VHH JM4, but not GPI-VHH E4 and JM2, on the surface of t

99 CR5 cells with GPI-VHH JM4, but not with GPI-VHH E4, confers resistance to both cell-free and T cell-

100 r, transduction of CEMss-CCR5 cells with GPI-VHH JM4, but not with GPI-VHH E4, confers resistance to

101 anel of heavy-chain-only antibody (Ab) V(H) (VHH) domains that neutralize Stx1 and/or Stx2 in cell-ba

102 the variable domain of heavy chain of HCAbs (VHH).

103 s (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent (VNA2-PA).

104 ively, these data suggest that heterodimeric VHH-based neutralizing agents may function through the f

105 nction, but functional testing of identified VHHs is laborious.

106 a lentiviral screening approach to identify VHHs that elicit a phenotype when expressed intracellula

107 over, structural elucidation of several IpaD-VHH complexes provided critical insights into tip comple

108 d camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emissi

109 eveloped a method to site-specifically label VHHs [the variable domain (VH) of a camelid heavy-chain

110 r even single-domain antibody fragments like VHHs will be reviewed.

111 dy validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and ident

112 en coupled to antigenic payloads, anti-MHCII VHH primed Ab responses against GFP, ubiquitin, an OVA p

113 rationale for the development of multivalent VHHs that target both toxins and are broadly neutralizin

114 For clinical applications, nanobodies (VHH) derived from heavy chain only antibodies from Camel

115 hage display vector and selected nanobodies (VHHs) against native Arabidopsis seed proteins.

116 A second neutralizing VHH (JKH-C7) recognizes a novel epitope.

117 lico modeling suggests that the neutralizing VHH binds the same residues on the Vgamma9Vdelta2 TCR as

118 ntially targeted by the broadly neutralizing VHHs as determined by competition ELISAs and 3D models o

119 structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at res

120 uctions of poliovirus with five neutralizing VHHs.

121 Two classes of neutralizing VHHs were identified recognizing distinct, non-overlappi

122 ents containing two linked Stx1-neutralizing VHHs or two Stx2-neutralizing VHHs were generally much m

123 1-neutralizing VHHs or two Stx2-neutralizing VHHs were generally much more potent at Stx neutralizati

124 rine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spo

125 consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against l

126 Cotransformation of VHH-IgA with the porcine joining chain and secretory com

127 sed vaccines and supports the development of VHH as anti-HIV-1 microbicides.

128 mined by competition ELISAs and 3D models of VHH-Env complexes derived from negative stain electron m

129 The crystal structure at 2.1-A resolution of VHH JM4 bound to HIV-1 YU2 gp120 stabilized in the CD4-b

130 ng demonstrates the increased versatility of VHH antibodies.

131 were obtained by promoting the isolation of VHHs with the slowest koff (off-rate selection).

132 iven the ease of manufacture and labeling of VHHs, we believe that this method could transform the ma

133 ells to prolong the circulatory half-life of VHHs.

134 ood cells by expressing chimeric proteins of VHHs with Glycophorin A or Kell.

135 Selection of VHHs recognizing BDE-47 was achieved by panning under ca

136 This set of VHHs should facilitate development of new therapeutic VN

137 cted for different nonoverlapping subsets of VHHs, allowing one to optimize the immunodetection of th

138 Recently, we reported on VHHs with in vivo activity against the protective antige

139 One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 stra

140 Of note, one VHH heterodimer could reduce Shigella hemolytic activity

141 argeted, but not antigen expression level or VHH affinity.

142 Nanobodies, or VHHs, that recognize poliovirus type 1 have previously b

143 by comparing sensors with randomly oriented VHH (with multiple exposed azide groups) to sensors with

144 e groups) to sensors with uniformly oriented VHH (with only a single azide group).

145 The two other VHHs, E1 and V1C7, bind epitopes adjacent to V5E1 but di

146 A phage VHH library was constructed, and seven VHH clones were s

147 The most potent VHH (Aa1) had a solution K(d) for BoNT/A Lc of 1.47 x 10

148 Here we present VHHs against botulinum neurotoxin A (BoNT/A) on the surf

149 Radiolabeled VHHs rapidly cleared the circulation (t1/2 approximately

150 The cross-reactive VHHs block binding of EF/LF to the protective antigen C-

151 ght gain compared with the piglets receiving VHH-IgG producing (dose 80 mg/d per pig) or wild-type se

152 ity were compared using the FMDV-recognizing VHH.

153 nes, producing varying levels of recombinant VHH or single-chain Fv antibody fragments fused to the h

154 inate current assay development, recombinant VHHs have a high potential as alternative reagents for t

155 The variable regions (VHH) in these heavy chain-only Abs demonstrate comparabl

156 we developed GPI-anchored variable regions (VHHs) of two heavy chain-only antibodies, JM2 and JM4, f

157 The variable regions (VHHs) of two heavy chain-only antibodies, JM2 and JM4, f

158 ide spacer to the sole neutralizing anti-RTB VHH to create VHH "heterodimers." As compared with equim

159 ntary neutralization pattern of two selected VHHs in combination covers 19 out of 21 HIV-1 strains fr

160 conclusion, a highly specific and sensitive VHH for 3-PBA was developed using sequences from immuniz

161 phage VHH library was constructed, and seven VHH clones were selected by competitive binding with 3-P

162 acids, we selected and characterized several VHHs that retain antigen binding capacity.

163 nking the VHHs with a GPI attachment signal, VHHs are targeted to the lipid rafts of the plasma membr

164 nking the VHHs with a GPI attachment signal, VHHs are targeted to the lipid rafts of the plasma membr

165 pite similar binding of Ly-6C/Ly-6G-specific VHH immunotoxin to granulocytes and monocytes, granulocy

166 ecific VHH, and one Stx1/Stx2 cross-specific VHH--was effective in preventing all symptoms of intoxic

167 produced a new collection of ricin-specific VHH heterodimers, as well as VHH homodimers, and charact

168 e-tagged VHH heterotrimer--one Stx1-specific VHH, one Stx2-specific VHH, and one Stx1/Stx2 cross-spec

169 er--one Stx1-specific VHH, one Stx2-specific VHH, and one Stx1/Stx2 cross-specific VHH--was effective

170 he facile identification of antigen-specific VHHs and their beneficial biochemical and economic prope

171 These prefusion F-specific VHHs represent promising antiviral agents against RSV.

172 Cytosolic expression of NP-specific VHHs (alphaNP-VHHs) disrupts virus replication at an ear

173 Among the 20 unique ricin-specific VHHs we identified, six had toxin-neutralizing activity:

174 Three neutralizing RTA-specific VHHs were each linked via a short peptide spacer to the

175 ralizing agent consisting of a double-tagged VHH heterotrimer--one Stx1-specific VHH, one Stx2-specif

176 The neutralizing Vgamma9Vdelta2 TCR VHH identified in this study might provide a novel appro

177 Thus, we conclude that VHH JM4, when targeted to the lipid rafts of the plasma

178 The VHH harbors remarkable amino acid substitutions in the f

179 The VHH heterodimers did differ from the homodimers in their

180 onstant domain and a reshaped surface at the VHH side, which normally associates with L chains in con

181 RTA interactions were influenced most by the VHH CDR3 (CDR, complementarity-determining region) eleme

182 ly the piglets receiving feed containing the VHH-IgA-based antibodies (dose 20 mg/d per pig) were pro

183 consists of one antigen-binding domain, the VHH, and two constant domains.

184 iosensors, and azides were introduced in the VHH to function as bioorthogonal reactive groups.

185 Moreover, the VHH heterodimers that were most effective at promoting r

186 Ala scanning of the VHH revealed only three "hot spot" side chains and addit

187 The versatility of the VHH scaffold and sortase-mediated covalent attachment of

188 properties of GO with the versatility of the VHH scaffold in the context of a flow system provides a

189 Piglets receiving the VHH-IgA-based antibodies in the feed showed a progressiv

190 and applicability, strongly suggest that the VHH antibody format will play a more prominent role in f

191 We demonstrate that the VHH heterodimers, but not homodimers were able to comple

192 philic, hence more soluble, character to the VHH but decrease the intrinsic stability of the domain.

193 In addition, the VHHs prevent RSV replication and lung infiltration of in

194 In all four complexes, the VHHs bind to a site on the top surface of the capsid pro

195 We show that by genetically linking the VHHs with a GPI attachment signal, VHHs are targeted to

196 We report that by genetically linking the VHHs with a GPI attachment signal, VHHs are targeted to

197 The neutralizing mechanisms of the VHHs and their potential use as quality control agents f

198 None of the VHHs made direct contact with residues involved in RTA's

199 A subset of the VHHs neutralized against EF and/or LF in murine macropha

200 Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the ca

201 The binding surfaces on the VHHs are surprisingly extensive, but despite the use of

202 ces on the virus, the binding surface on the VHHs is unique for each VHH.

203 These VHHs recognized the in situ tip complex and modulated th

204 Six of these VHHs are cross-reactive against both EF and LF and recog

205 Crystal structures of these VHHs in complex with prefusion F show that they recogniz

206 best immunoassay developed with one of these VHHs showed an IC(50) of 1.4 ng/mL (limit of detection (

207 One of these VHHs, V5E1, ranks as one of the most potent ricin-neutra

208 Based on their specificity, these VHHs fall into two distinct groups.

209 We show that these VHHs can target NP in living cells and perturb NP's func

210 The use of this VHH antibody reagent immobilized onto a Au electrode for

211 ciated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early in

212 ir respective monovalent monomers, all three VHH heterodimers had higher affinities for ricin and, in

213 -ray crystal structures of each of the three VHHs (E1, V1C7, and V5E1) in complex with RTA.

214 negative-sense RNA viruses are vulnerable to VHHs uniquely specific for their respective nucleoprotei

215 rved in which the final complex includes two VHH domains for every caffeine molecule.

216 tag present at two sites on each of the two VHH heterodimer molecules that bind to each toxin molecu

217 Two VHHs were tested in this study: one recognizing foot-and

218 We used VHHs to explore the possibility of imaging inflammation

219 We tested T cell activation using VHHs that target distinct APC populations; anti-MHCII ad

220 antibody composed of 2 heavy-chain-only VH (VHH) binding domains against both TcdA and TcdB (designa

221 izing unique structures of expanded virions, VHH binding permitted a more detailed view of the virus

222 Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked t