ライフサイエンスコーパス: bnAb

1 bnAbs appear very late, and patients are typically not p

2 bnAbs are therefore expected to evolve only when the B c

3 We describe two genetically similar V(H)6-1 bnAb clonotypes from the same individual that exhibit di

4 circumvent the difficult roadblocks in HIV-1 bnAb induction by vaccination.

5 hemagglutinin nanoparticle elicited group 1 bnAbs, but only in IGHV1-69 mice.

6 lbow region are frequently observed in HIV-1 bnAbs and MD simulations show that such FWR mutations al

7 mined the maturation pathway of select HIV-1 bnAbs from acute infection through neutralizing antibody

8 s alter interdomain flexibility in two HIV-1 bnAbs.

9 diverse precursors of CD4 binding site HIV-1 bnAbs.

10 duction of affinity-matured and potent HIV-1 bnAbs.

11 (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of muc

12 Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co

13 e set of potential antibody precursors for a bnAb with dominant HCDR3 contacts.

14 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agon

15 ative study of the therapeutic efficacy of a bnAb in acutely and chronically SHIV-infected macaques.

16 Structures of a bnAb precursor, a bnAb, and the vaccine-elicited antibod

17 f incomplete neutralization the ability of a bnAb to mediate sterilizing protection diminishes.

18 Structures of a bnAb precursor, a bnAb, and the vaccine-elicited antibody revealed the pre

19 hat influence the evolution of high-affinity bnAbs remain elusive.

20 lly influence the evolution of high-affinity bnAbs.

21 virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antige

22 velope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing divers

23 Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to th

24 on of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza

25 broadly neutralizing monoclonal antibodies (bnAbs).

26 ge in human broadly neutralizing antibodies (bnAbs) against both HIV and influenza virus, suggesting

27 s to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains.

28 Broadly neutralizing antibodies (bnAbs) against HIV-1 protect from infection and reduce v

29 Broadly neutralizing antibodies (bnAbs) against HIV-1 provide critical insights into co-e

30 a class of broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV).

31 rization of broadly neutralizing antibodies (bnAbs) against influenza virus identified the conserved

32 on of human broadly neutralizing antibodies (bnAbs) against influenza virus provide valuable insights

33 nduction of broadly neutralizing antibodies (bnAbs) against this diversity by vaccination likely requ

34 a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protec

35 iters by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C in

36 target for broadly neutralizing antibodies (bnAbs) and the focus for design of an antibody-based HIV

37 rized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities fo

38 Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccinati

39 tigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies

40 HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against HIV infe

41 nduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse vari

42 Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents.

43 Broadly neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals

44 r target of broadly neutralizing antibodies (bnAbs) developed during infection in some individuals.

45 ials, HIV-1 broadly neutralizing antibodies (bnAbs) effectively lower plasma viremia and delay virus

46 Broadly neutralizing antibodies (bnAbs) elicited in HIV-1(+) elite neutralizers typically

47 review how broadly neutralizing antibodies (bnAbs) exploit these evolutionary constraints to protect

48 it broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine develo

49 HIV broadly neutralizing antibodies (bnAbs) have been shown to occasionally display unusual v

50 er of HIV-1 broadly neutralizing antibodies (bnAbs) have demonstrated remarkable efficacy as prophyla

51 Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus's enve

52 volution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vacc

53 nduction of broadly neutralizing antibodies (bnAbs) inform most current vaccine strategies for influe

54 rs of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but curre

55 nduction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal.

56 citation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal.

57 hat trigger broadly neutralizing antibodies (bnAbs) is a priority as bnAbs are considered key to elic

58 ren develop broadly neutralizing antibodies (bnAbs) more frequently and earlier than adults do.

59 nduction of broadly neutralizing antibodies (bnAbs) targeting conserved epitopes following vaccinatio

60 rity of the broadly neutralizing antibodies (bnAbs) targeting HIV-1 have been isolated from non-subty

61 etection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a si

62 on of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of

63 Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophyla

64 tanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infe

65 nduction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge.

66 tanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop

67 ely require broadly neutralizing antibodies (bnAbs) with maximum breadth and potency to ensure therap

68 l vaccines, broadly neutralizing antibodies (bnAbs), and therapeutics.

69 target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited

70 cts develop broadly neutralizing antibodies (bnAbs), such as the potent VRC01-class bnAbs, that neutr

71 ies, called broadly neutralizing antibodies (bnAbs), that have a high breadth and can neutralize mult

72 us-known as broadly neutralizing antibodies (bnAbs)-could protect against highly mutable pathogens.

73 that induce broadly neutralizing antibodies (bnAbs).

74 v V3/glycan broadly neutralizing antibodies (bnAbs).

75 or inducing broadly neutralizing antibodies (bnAbs).

76 n (Env) for broadly neutralizing antibodies (bnAbs).

77 ents evolve broadly neutralizing antibodies (bnAbs).

78 generating broadly neutralizing antibodies (bnAbs).

79 t to elicit broadly neutralizing antibodies (bnAbs).

80 lls and HIV broadly neutralizing antibodies (bnAbs).

81 zed by most broadly neutralizing antibodies (bnAbs).

82 on of HIV-1 broadly neutralizing antibodies (bnAbs).

83 ross-reactive broadly neutralizing antibody (bnAb) and not by nonneutralizing antibodies.

84 on of passive broadly neutralizing antibody (bnAb) infusion and active vaccination promises to provid

85 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 prim

86 cacy of HIV-1 broadly neutralizing antibody (bnAb) therapies may be compromised by the preexistence o

87 elopment of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens becau

88 The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to preve

89 t from an HIV broadly neutralizing antibody (bnAb), PG9.

90 HIV-specific broadly neutralizing antibody (bnAb), using computational methods developed specificall

91 y, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env.

92 of immunization strategies to induce V2 apex bnAb responses.

93 The evolution of apex bnAbs from one donor (CAP256) has been studied in detail

94 ation approaches capable of inducing V2-apex bnAbs against HIV-1.

95 lite neutralizers are susceptible to V2-apex bnAbs.

96 ralizing antibodies (bnAbs) is a priority as bnAbs are considered key to elicitation of a protective

97 afforded by analyses of recombinant Ig-based bnAb structures, it became apparent that key functional

98 tocol allows many evolving B cells to become bnAbs via diverse evolutionary paths.

99 ructural studies can define contacts between bnAbs and Env, only functional studies can define mutati

100 nt of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination.

101 infection, we used LSEVh-LS-F, a bispecific bnAb targeting the CD4 binding site and CD4-induced epit

102 Env interaction, we showed that the broadest bnAbs targeted more conserved epitopes (Spearman's rho =

103 ere screened on the basis of high binding by bnAbs and low binding by nonneutralizing antibodies.

104 The variable recognition of FP by bnAbs thus provides insights for vaccine design.

105 t different conformations for recognition by bnAbs, which enables approach to Env from diverse angles

106 s currently in clinical trial as a candidate bnAb vaccine priming immunogen.

107 We conclude that infusion of CD4bs bnAb CH31 at birth does not interfere with de novo antib

108 single infusion of CD4 binding site (CD4bs) bnAb administered at birth on de novo antibody responses

109 Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict

110 mise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on

111 single intravenous coadministration of CH31 bnAb at birth.

112 Because many VRC01-class bnAb SHMs are not required for broad neutralization, hig

113 Mature VRC01-class bnAbs, including VRC-PG04, accumulate very high SHM leve

114 dies (bnAbs), such as the potent VRC01-class bnAbs, that neutralize diverse HIV-1 strains.

115 breadth and antiviral efficacy by combining bnAbs for therapeutic indications.

116 wever, some HIV-infected individuals develop bnAbs after approximately 2-4 years of infection, enabli

117 receptor usage restriction and the different bnAb susceptibilities.

118 orientation interfered with V3 loop-directed bnAb binding.

119 A smaller proportion of the head-directed bnAbs were polyreactive.

120 profiles of a set of stem and head-directed bnAbs.

121 cially to variable loop 3 (V3 loop)-directed bnAbs, than exclusively CCR5-utilizing strains in some,

122 ramework for development of HA stem-directed bnAbs, sequence differences in CDR H3 junctional regions

123 To date, most of the discovered bnAbs bind either to conserved sites in the stem region

124 nogens/regimens for effectiveness in driving bnAb responses.

125 d diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolut

126 t mice resulting in the expansion of durable bnAb memory and long-lived plasma cells.

127 l flexibility and paratope plasticity during bnAb development.

128 aracteristics in infected infants with early bnAb responses will provide key information about antige

129 identify viral factors associated with early bnAb responses.

130 to date, no vaccination regimen has elicited bnAbs against this region.

131 nAb development, the challenges of eliciting bnAbs via immunizations, and the putative central roles

132 e review the progress to date in elucidating bnAb B cell lineages in HIV-1 infection, discuss new res

133 mbled into variable region exons that encode bnAb precursors), have been engineered to evaluate novel

134 ould, in principle, support germline-encoded bnAb elicitation using a single recombinant hemagglutini

135 vaccine strategies that specifically engage bnAb precursors and subsequently select for improbable m

136 During their evolution, bnAbs acquire an abundance of improbable amino acid subs

137 specificities approaching those of existing bnAbs.

138 ely need to incorporate strategies to expand bnAb precursor pools.

139 se IgH and IgL loci has been used to express bnAbs in mice.

140 ch B cell developmental blocks by expressing bnAbs conditionally in mature B cells.

141 imers suitable for use as antigenic bait for bnAb isolation, structural studies, and use as potential

142 functional improbable mutations critical for bnAb development.

143 We discuss implications of our findings for bnAb affinity maturation mechanisms.

144 ct for key improbable mutations required for bnAb development.

145 omplete neutralization is not imperative for bnAbs to prevent infection but that with increasing leve

146 e and demonstrate that this would select for bnAbs.

147 Here, we review insights gained from bnAb KI studies regarding the regulation and induction o

148 lex maturation pathways required to generate bnAbs from these precursors.

149 ls of either a CD4 binding site or V3-glycan bnAb lineage.

150 Similar to human V3/glycan bnAbs, certain monoclonal antibodies (mAbs) elicited by

151 post-infection suggesting factors governing bnAb induction in infants are distinct from adults.

152 n vivo, to further facilitate vaccine-guided bnAb induction studies.

153 zing antibodies (non-nAbs), which may hinder bnAb induction.

154 known about the immunological process of HIV bnAb development, the challenges of eliciting bnAbs via

155 Here, we show that HIV bnAb-engineered primary mouse B cells can be adoptively

156 iking amount of somatic hypermutation in HIV bnAbs led to the hypothesis that T follicular helper (Tf

157 mework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibo

158 The generation of HIV bnAbs may be one of the greatest feats of the human immu

159 as a strategy for durable elicitation of HIV bnAbs to protect against infection and as a contributor

160 pected to prove useful for the design of HIV bnAbs, where the computation of the potency must be acco

161 of Tfh cells and GC in the generation of HIV bnAbs.

162 However, bnAb-lipid interactions are often studied in systems tha

163 to immunize mouse models that express human bnAb precursors and assess whether the vaccine can conve

164 serum neutralizing HIV-1 antibodies in human bnAb precursor knock-in mice and wild-type macaques vacc

165 Antibody sequences elicited in human bnAb precursor knock-in mice encoded functional improbab

166 IGHV1-69, which shows biased usage in human bnAbs targeting the hemagglutinin stalk of group 1 influ

167 ementarity-determining region loops of human bnAbs FI6v3 and CR9114 against the HA stem.

168 d pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture

169 most potent and most broadly reactive human bnAbs, RVC20, in complex with its target domain III of t

170 M structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also

171 In bnAb precursor knock-in mice, we isolated a vaccine-elic

172 of the GC and Tfh-cell processes involved in bnAb generation, including the difficulty of quantifying

173 ion of tier 2 HIV-1 does not always indicate bnAb induction.

174 In some HIV-1-infected individuals, bnAbs evolved from precursor antibodies through affinity

175 distant variants is shown to robustly induce bnAbs that focus on conserved elements of the target epi

176 However no vaccine was able so far to induce bnAbs demanding their expensive biotechnological product

177 urrent vaccine strategies have yet to induce bnAbs in humans.

178 To induce bnAbs, a vaccine must mediate a similar antibody maturat

179 ctural analyses reveal that, for this infant bnAb, substitutions in the kappa chain were critical for

180 lation between the fast clearance of infused bnAbs and the treatment failure in the acute period of S

181 lation between the fast clearance of infused bnAbs and treatment failure during the acute period of i

182 cquired improbable mutations, could initiate bnAb B cell lineages and select for key improbable mutat

183 accine can convert precursor antibodies into bnAbs.

184 capable of identifying impediments limiting bnAb induction and ranking vaccine strategies for their

185 immunologic tolerance mechanisms in limiting bnAb development.

186 allowed immune tolerance mechanisms limiting bnAb production to be elucidated and strategies to overc

187 modeling suggested that the primary V3 loop bnAb epitope is equally accessible among CCR5- and CXCR4

188 erminant does not directly influence V3 loop bnAb sensitivity.

189 ope V1 loop and the antibody impacts V3 loop bnAb susceptibility in some cases.

190 models may be useful for predicting V3 loop bnAb therapy efficacy.

191 sma virus level, respectively, after V3 loop bnAb treatment.

192 respectively, after treatment with a V3 loop bnAb.

193 that predict treatment efficacy with V3 loop bnAbs.IMPORTANCE The efficacy of HIV-1 broadly neutraliz

194 ble, especially to variable loop 3 (V3 loop) bnAbs in some, but not all, instances.

195 increase thermal stability while maintaining bnAb antigenicity.

196 Many bnAbs isolated from HIV-1-infected individuals are encod

197 (designed to bind progressively more mature bnAb precursors) to initiate affinity maturation.

198 ced precursor V(D)J rearrangements of mature bnAbs or unrearranged germline V, D, J segments (that ca

199 n an early intermediate and affinity-matured bnAb against autologous and heterologous Tier-2 viruses,

200 ggest that an effective strategy to maximize bnAb evolution is through a sequential immunization prot

201 uction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain compl

202 For most bnAbs, mutations at only a small fraction of structurall

203 ficity of lipid interactions of an anti-MPER bnAb (4E10) in an intact membrane context, we determine

204 ar mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived g

205 in Env affect neutralization of HIV by nine bnAbs targeting five epitopes.

206 infections.IMPORTANCE Currently, there is no bnAb-based monotherapy that has been reported to clear t

207 This study evaluates the novel bnAb N6-LS alone or in combination with the bnAb PGT121,

208 wnselection after hierarchical clustering of bnAb neutralization titers.

209 ht into immunologic mechanisms of control of bnAb development.

210 elected panels to represent the diversity of bnAb neutralization profiles and Env neutralization sens

211 The efficacy of bnAb-based therapies and vaccines depends in part on how

212 monstrated the safety and the feasibility of bnAb administration to achieve biologically relevant lev

213 understanding the immunologic mechanisms of bnAb induction, and address issues relevant to the use o

214 From these studies has come a picture of bnAb development that has led to new insights in host-pa

215 y be attributed to the unusual properties of bnAb variable regions, such as poly-reactivity and long

216 ore explore the functional sequence space of bnAb C05, which targets the receptor-binding site (RBS)

217 -electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, wit

218 incomplete neutralization for the ability of bnAbs to mediate protective effects in vivo, however, is

219 ys epitopes recognized by a diverse array of bnAbs.

220 Several classes of bnAbs directed to the conserved HA stem were found in mu

221 A recent study reports the development of bnAbs in an elite controller that, along with the help o

222 time of HIV-1 transmission to development of bnAbs.

223 al tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more va

224 Under such circumstances the evolution of bnAbs is much more consistent.

225 that entropically disfavor the evolution of bnAbs.

226 rtoire markedly facilitates the evolution of bnAbs.

227 by vaccination may speed up the evolution of bnAbs.

228 distances may best promote the evolution of bnAbs.

229 nipulate the production and/or expression of bnAbs in vivo, to further facilitate vaccine-guided bnAb

230 ame apparent that key functional features of bnAbs often are problematic for their elicitation in mic

231 pt has emerged that one path to induction of bnAbs is to define the viral and immunologic events that

232 Induction of bnAbs requires vaccine strategies that specifically enga

233 es regarding the regulation and induction of bnAbs, and discuss new Ig KI methodologies to manipulate

234 ell maturation pathways towards induction of bnAbs.

235 e mechanism for the disparate performance of bnAbs in different periods of SHIV infection, we used LS

236 rotection strategies, we assessed a range of bnAbs and nnAbs for their potential to block ex vivo cha

237 Mapping the epitope specificities of bnAbs provides useful information for vaccine design.

238 ould be important for the therapeutic use of bnAbs and eventually towards the functional cure of HIV/

239 tant implications for the therapeutic use of bnAbs to treat acute HIV infections.IMPORTANCE Currently

240 be generally applicable for expressing other bnAbs that are under negative selection during B cell de

241 accination and that a combination of passive bnAb infusion and active HIV-1 Env vaccination is a viab

242 d animals and was linked to declining plasma bnAb levels over time.

243 Plasma bnAbs targeting V2-apex on the env are predominant in in

244 Infected infants develop plasma bnAbs frequently and as early as 1-year post-infection s

245 Herein, we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants a

246 ivariant infection is associated with plasma bnAbs targeting diverse autologous viruses.

247 The Env mutations selected by two pooled bnAbs were similar to those expected from the combinatio

248 Some of the most potent bnAbs target a quaternary epitope at the apex of the sur

249 a mouse model and bound a range of potential bnAb-precursor human naive B cells in ex vivo screens.

250 esis of Env to play out all of the potential bnAb escape strategies and in doing so define the functi

251 cine strategies for their ability to promote bnAb development.

252 d immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a rang

253 In this regard, bnAb KI models expressing deduced precursor V(D)J rearra

254 nd CD4-induced epitopes, as a representative bnAb and assessed its potential therapeutic benefit in c

255 Because stem-directed serum bnAbs are much less abundant than head-directed ones, we

256 breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human

257 in nonhuman primates, in contrast to single bnAbs.

258 ns for focusing immune responses to specific bnAb epitopes.

259 The solid protection provided by specific bnAbs clearly demonstrates their superior potential over

260 CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking

261 members of a family of oligomannose-specific bnAbs and their putative common germline precursor when

262 enic mimicry to elicit oligomannose-specific bnAbs to HIV-1.

263 the interactions and mechanism of anti-stem bnAb CR6261, we selected and optimized small molecules t

264 ected ones, we hypothesized that the HA stem bnAbs may be autoreactive and thus eliminated through th

265 Although several stem bnAbs are being evaluated in clinical trials, antibodies

266 Most of the stem bnAbs we examined bound autoantigens; several showed sta

267 owever, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated.

268 at the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher

269 nother donor who developed V2-apex targeting bnAbs.

270 The tested bnAbs show lower thermostability than their unmutated an

271 major problem with such mouse models is that bnAb expression often hinders B cell development.

272 ions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the

273 e of somatic hypermutation in broadening the bnAb response.

274 onses were not significantly enhanced in the bnAb-treated animals compared to control animals, arguin

275 and optimized small molecules that mimic the bnAb functionality.

276 eal that the lead compound recapitulates the bnAb hotspot interactions.

277 bnAb N6-LS alone or in combination with the bnAb PGT121, in rhesus macaques that were chronically in

278 t allowed for complete neutralization by the bnAbs.

279 o those expected from the combination of the bnAbs's independent action.

280 the neutralizing potency displayed by these bnAbs.

281 ne of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance.

282 that bind with moderate to high affinity to bnAb B cell precursors, and with higher affinity to prec

283 We found that sites corresponding to bnAb epitopes were as variable as other accessible, non-

284 l bifurcation, with only one path leading to bnAb development.

285 ibody generation, and how this is related to bnAb development, and considers the implications for HIV

286 ir acquisition represents a key roadblock to bnAb development.

287 tro, these immunogens bound more strongly to bnAb precursors once the precursor acquired the desired

288 t binds to pockets in the HA stem similar to bnAbs FI6v3 and CR9114, cyclic peptide P7, and small-mol

289 In the current study, we selected two bnAbs, PGT121 and 3BNC117, as they incompletely neutrali

290 ing complex glycosylation of Env affected V2 bnAb recognition, as previously described, but also nota

291 A number of Env-stabilizing mutations and V2 bnAb-enhancing mutations were identified in Env, but the

292 ions together increased neutralization by V2 bnAb and eliminated binding by V3 crown antibodies.

293 that when mutations outside V2 increased V2 bnAb recognition, they often also increased Env stabilit

294 e stability of mutant Envs and the MPN of V2 bnAb, PG9, as well as an inverse correlation between sta

295 relates to neutralization sensitivity to V2 bnAbs and V3 crown antibodies that engage subunit interf

296 ow region reversion mutations in a glycan-V3 bnAb modestly reduces potency against an autologous viru

297 In addition to the effect on plasma viremia, bnAb administration resulted in significantly reduced pr

298 ted common ancestor (UCA) of the human VRC26 bnAb in transgenic mice.

299 Despite much work, the mechanisms by which bnAbs emerge remain uncertain.

300 While bnAbs are highly effective against cell-free virus, they