US2014322269A1PendingUtilityA1
Engineered outer domain (eod) of hiv gp120 and mutants thereof
Est. expiryOct 12, 2031(~5.2 yrs left)· nominal 20-yr term from priority
C07K 14/005G01N 33/564C12N 2740/16122C12N 2740/16134A61K 39/12A61K 39/21A61K 38/00
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Abstract
The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.
Claims
exact text as granted — not AI-modified1 . A non-naturally occurring protein comprising an engineered outer domain (eOD) mutation advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs), wherein the protein comprises any one of:
(a) ODm1(D386)
RPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTGAGHCNISRAKWNN
TLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFNSTWFNSTWS
TEGSNNTEGSDTITLPCRPAPPPHCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWR
SE
(b) ODm1(N386)
RPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTGAGHCNISRAKWNN
TLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
TEGSNNTEGSDTITLPCRPAPPPHCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWR
SE
(c) c1
DTITLPCRPAPPPHCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWRSGLSGPVVST
QLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTGAGHCNISRAKWNNTLKQIA
SKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFNSTWFNSTWS
(d) c2
GEFFYCDSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRPAPPPHCSSNITGLLLTRDGG
NSNNESEIFRPGGGDMRDNWRSGLSGPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIV
QLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSF
NCG
(e) c1d1_N386D (also called “eOD_N386D”)
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFNSTWFNSTWS
(f) c1d1_b10disulf
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVCRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASC
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFNSTWFNSTWS
(g) c1d1_v2
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMAGMPRCGGGAVSTQLL
LNGSLAEEEVVCRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASCL
REQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFNSTWF
(h) c1d1_minglyc (also called “eOD_minglyc” and “c1d1_448_262 glycan”)
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLDTSVEIDCTGAGHCDISRAKWDNTLKQIASK
LREQFGNDKTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFDSTWFDSTWS
(i) c2d1
GEFFYCDSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRPAPPPHCSSNITGLILTRDGG
NSNNESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEEVVIRSVNFTDNAKSICV
QLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSF
NCG
(j) c2d2
GEFFYCDSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRPAPPPHCSSNITGLILTRDGG
NSNNESEIFRPGGGDMRCGARSGIAGTVVSTQLLLNGSLAEEEVVIRSVNFTDNAKCIIV
QLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSF
NCG
(k) c2d1_b10disulf
GEFFYCDSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRPAPPPHCSSNITGLILTRDGG
NSNNESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEEVVCRSVNFTDNAKSICV
QLNTSVEINCTGAGHCNISRAKWNNTLKQIASCLREQFGNNKTIIFKQSSGGDPEIVTHSF
NCG
or any combination thereof.
2 . A non-naturally occurring protein comprising an eOD mutation to improve binding of mature VRC01, wherein the protein comprises any one of:
(a) eOD
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(b) eODN276D (= “eOD_D(−)”)
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSV D FTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(c) eOD_N276D_N463D (= “eOD VD(−)”)
DTITLPCRPAPPPHCSSNITGLILTRDGGNSN D ESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSV D FTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(d) eOD_L260F
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
F LNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(e) eOD_L260F_N276D
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
F LNGSLAEEEVVIRSV D FTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(f) eOD_L260F_N276D_N463D
DTITLPCRPAPPPHCSSNITGLILTRDGGNSN D ESEIFRPGGGDMRDIARCQIAGTVVSTQL
F LNGSLAEEEVVIRSV D FTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(g) eOD_I478N
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRD N ARCQIAGTVVSTQ
LLLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIAS
KLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(h) eOD_Δ356
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(i) eOD_S387T
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCN T TQLFNSTWFNSTWS
(j) eOD_V270I
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEE I VIRSVNFTDNAKSICVQLNTSVE1NCTGAGHCNISRAKWNNTLKQIASKL
REQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(k) eOD_T257S_L260F_S375W
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVS S QL
F LNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTH W FNCGGEFFYCNSTQLFNSTWFNSTWS
(l) eOD_T257S_L260F_S375W_N276D
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVS S QL
F LNGSLAEEEVVIRSV D FTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTH W FNCGGEFFYCNSTQLFNSTWFNSTWS
(m) eOD_T257S_L260F_S375W_N276D_N463D
DTITLPCRPAPPPHCSSNITGLILTRDGGNSN D ESEIFRPGGGDMRDIARCQIAGTVVS S QL
F LNGSLAEEEVVIRSV D FTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTH W FNCGGEFFYCNSTQLFNSTWFNSTWS
or any combination thereof.
3 . The protein of claim 1 wherein the eOD mutation further improves germline VRC01 binding.
4 . A non-naturally occurring protein comprising an eOD variant engineered to improve binding to germline VRC01 and/or other VI-11-2 antibodies comprising any one of:
(a) eOD_VH1-2_v1.0
DTITLPCRPAPPPHCSSNITGLILTRDGGTSDDKTEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSEDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTWS
(b) eOD_VH1-2_v2.0
DTITLPCRPAPPPHCSSNITGLILTRGGGISDDKTEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSEDFRDNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTWS
(c) eOD_VH1-2_v2.1 (eOD_VH1-2_v2.0 + D276N + R278T)
DTITLPCRPAPPPHCSSNITGLILTRGGGISDDKTEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSE N F T DNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTWS
(d) eOD_VH1-2_v3.0 (eOD_VH1-2_v2.0 + G471S + S401#)
DTITLPCRPAPPPHC SSNITGLILTRGGGISDDKTEIFRP S GGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSEDFRDNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(e) eOD_VH1-2_v3.1 (eOD_VH1-2_v2.0 + K357R + S401#)
DTITLPCRPAPPPHCSSNITGLILTRGGGISDDKTEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSEDFRDNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN# R TIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(f) eOD_VH1-2_v4.0 (eOD_VH1-2_v3.0 + K464D + L260F + K357R)
DTITLPCRPAPPPHC SSNITGLILTRGGGISDD D TEIFRPSGGDMRDIARCQIAGTVVSTQL
F LNGSLAEEEVVIRSEDFRDNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN# R TIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(g) eOD_VH1-2_v4.1 (eOD_VH1-2_v3.0 + G457A + K464N + L260F + K357R)
DTITLPCRPAPPPHCSSNITGLILTR A GGISDD N TEIFRPSGGDMRDIARCQIAGTVVSTQL
F LNGSLAEEEVVIRSEDFRDNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN# R TIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(h) eOD_VH1-2_v4.2 (eOD_VH1-2_v3.0 + K464N + K357R)
DTITLPCRPAPPPHCSSNITGLILTRGGGISDDNTEIFRPSGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSEDFRDNSKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFSQSLGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(i) eOD_VH1-2_v5.0 (eOD_VH1-2_v4.0 + I460V + E275V + S281A + L365S)
DTITLPCRPAPPPHCSSNITGLILTRGGGVSDDDTEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFSQSSGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(j) eOD_VH1-2_v5.1
DTITLPCRPAPPPHCSSNITGLILTRGGGVSDDDTEIFRPAGGDMRDIARCQIAGTVVSTQ
LFLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIAS
KLREQFGN#RTIIFSQSSGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDSTW#
(k) eOD_VH1-2_v5.2 (truncated form of v5.0)
DTITLPCRPAPPPHCSSNITGLILTRGGGVSDDDTEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFSQSSGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFD####
(l) eOD_VH1-2_v6.0
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(m) eOD_VH1-2_v6.1 (v6.0 + V460N)
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(n) eOD_VH1-2_v6.2 (v6.0 + T465S)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDESEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(o) eOD_VH1-2_v6.3 (v6.0 + S471G)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPGGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(p) eOD_VH1-2_v6.4 (v6.0 + F260L)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(q) eOD_VH1-2_v6.5 (v6.0 + R278T)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(r) eOD_VH1-2_v6.6 (v6.0 + R357K)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(s) eOD_VH1-2_v6.7 (v6.0 + F371I)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEIVTHSFNCGGEFFYCDSTQLFNSTWFNST##
(t) eOD_VH1-2_v6.8 (v6.0 “minglyc”)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNDETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLDTSVEIDCTGAGHCDISRAKWDNTLKQIASK
LREQFGD#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFDSTWFDST##
(u) eOD_VH1-2_v7.0 (v6.0 + D463N + D386N)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(v) eOD_VH1-2_v7.1 (v7.0 + V460N)
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(w) eOD_VH1-2_v7.2 (v7.0 + T465S)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNESEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(x) eOD_VH1-2_v7.3 (v7.0 + S471G)
DTITLPCRPAPPPHC SSNITGLILTRDGGVSNNETEIFRPGGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(y) eOD_VH1-2_1
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(z) eOD_VH1-2_v7.5 (v7.0 + R278T)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(aa) eOD_VH1-2_v7.6 (v7.0 + R357K)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#KTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(bb) eOD_VH1-2_v7.7 (v7.0 + F371I)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(cc) eOD_VH1-2_v7.8 (v7.0 + D276N + R278T)
DTITLPCRPAPPPHCSSNITGLILTRDGGVSNNETEIFRPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(dd) eOD_RheVH1-2_v1.0
DTITLPCRPAPPPHCSSNITGLILTRAGGVSDNNTEIFFPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFSQSTGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(ee) eOD_RheVH1-2_v2.0
DTITLPCRPAPPPHCSSNITGLILGRAGGASDDNTEIFYPSGGDMRDIARCQIAGTVVSTQ
LFLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIAS
KLREQFGN#RTIIFSQSTGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTW#
(ff) eOD_RheVH1-2_v2.1
DTITLPCRPAPPPHCSSNITGLILTRAGGVSNNETEIFFPSGGDMRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGN#RTIIFKQSSGGDPEFVTHSFNCGGEFFYCNSTQLFNSTWFNST##
(gg) core_gp120_VH1-2_v1.0
VWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVELENVTENFNMWKNN
MVEQMHEDIISLWDQSLKPCVKLTGGSVITQACPKISFEPIPIHYCAPAGFAILKCKDKKF
NGKGPCSNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFADNAKTIIVQLNESVEI
NCTRPNNGGSGSGGDIRQAHCNLSRAKWNDTLNKIVIKLREQFGNKTIVFKHSSGGDPEI
VTHSFNCGGEFFYCNSTQLFNSTWNVTEESNNTVENNTITLPCRIKQIINMWQKVGRAM
YAPPIRGQIRCSSNITGLLLTRDGGPEDNKTEVFRPGGGDMRDNWRSELYKYKVVKIE
(hh) core_gp120_VH1-2_v2.0
VWKDATTTLFCASDAKAHETEVHNVWATHACVPTDPNPQEVELKNVTENFNMWKNN
MVEQMHEDIISLWDQSLKPCVKLTGGSVITQACPKVSFEPIPIHYCAPAGFAILKCKDKK
FNGKGPCSNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSEDFRNNAKIIIVQLNESVEI
NCTGAGHCNLSRAKWNDTLNKIVIKLREQFGNKTIVFKHSSGGDPEIVTHSFNCGGEFFY
CNSTQLFNSTWNVTEESNNTVENNTITLPCRIKQIINMWQEVGRAMYAPPIRGQIRCSSNI
TGLLLIRDGGPEDNKTEIFRPGGGDMRDNWRSELYKYKVVKIE
(ii) core_gp120_VH1-2_v2.1
VWKDATTTLFCASDAKAHETEVHNVWATHACVPTDPNPQEVELKNVTENFNMWKNN
MVEQMHEDIISLWDQSLKPCVKLTGGSVITQACPKVSFEPIPIHYCAPAGFAILKCKDKK
FNGKGPCSNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSEDFRNNAKIIIVQLNESVEI
NCTGAGHCNLSRAKWNDTLNKIVIKLREQFGNKTIVFSHSSGGDPEFVTHSFNCGGEFF
YCNSTQLFNSTWNVTEESNNTVENNTITLPCRIKQIINMWQEVGPIRGQIRCSSNITGLLLI
RDGGAEDNKTEIFRPGGGDMRDNWRSELYKYKVVKIE
(jj) full_gp120_BaL_VH1-2_v1.0
MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYYGVPVWKEATTTLFCA
SDAKAYDTEVHNVWATHACVPTDPNPQEVELENVTENFNMWKNNMVEQMHEDIISL
WDQSLKPCVKLTPLCVTLNCTDLRNATNGNDTNTTSSSREMMGGGEMKNCSFKITTNI
RGKVQKEYALFYELDIVPIDNNSNNRYRLISCNTSVITQACPKISFEPIPIHYCAPAGFAIL
KCKDKKFNGKGPCSNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFADNAKTIIV
QLNESVEINCTRPNNNTRKSIHIGPGRALYTTGEIIGDIRQAHCNLSRAKWNDTLNKIVIK
LREQFGNKTIVFKHSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWNVTEESNNTVENNT
ITLPCRIKQIINMWQKVGRAMYAPPIRGQIRCSSNITGLLLTRDGGPEDNKTEVFRPGGG
DMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQ
(kk) eOD_VH1-2_VH1-8_v1.0
DTITLPCRPAPPPHCSSNITGLILTRLGGVSNDETEIFKPSGGDWRDIARCQIAGTVVSTQL
FLNGSLAEEEVVIRSVDFRDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNRTIIFKQSSGGDPEFVTHSFNCGGEFFYCDSTQLFNSTWFNST
or any combination thereof.
5 . A non-naturally occurring protein comprising an eOD variant engineered to improve binding to germline VRC01 to eOD comprising at least one mutation relative to eOD (=c1d1) in the eOD variants in this section listed below, in both eOD numbering (left column) and HxB2 numbering (right column), wherein the HxB2 numbering uniquely defines a position in any HIV Env sequence once it has been aligned to the HxB2 sequence, wherein the mutation is selected from the table consisting of:
eOD_mut_id
eOD_numbering
HxB2_numbering
1
A84S
A281S
2
D27A
D457A
3
D27G
D457G
4
E34D
E464D
5
E34K
E464K
6
E34N
E464N
7
G41S
G471S
8
L63F
L260F
9
N30A
N460A
10
N30I
N460I
11
N30T
N460T
12
N30V
N460V
13
N32D
N462D
14
N33D
N463D
15
N79D
N276D
16
N92D
N289D
17
N98D
N295D
18
R39F
R469F
19
R39Y
R469Y
20
S35T
S465T
21
T25G
T455G
22
T81R
T278R
23
V78E
V275E
24
I145F
I371F
25
K131R
K357R
26
K136S
K362S
27
N106D
N332D
28
N113D
N339D
29
N129D
N355D
30
N130#
N356#
31
N160D
N386D
32
N166D
N392D
33
N171D
N397D
34
S139L
S365L
35
S139T
S365T
36
S172#
S398#
37
S175#
S401#
38
T173#
T399#
39
W174#
W400#
or any combination thereof.
6 . A non-naturally occurring protein comprising a mutation and/or modification in core_gp120_VH1-2_v2.0 and core_gp120_VH1-2_v2.1 relative to core_gp120_VH1-2_v1.0, wherein the mutation and/or modification improves binding of core gp120 to germline VH1-2 antibodies, wherein the mutation and/or modification is selected from the group consisting of:
(a) removing a glycosylation site at position 276 in any HIV Env construct from any strain (b) mutation to D at position 47 (c) mutation to H at position 61 (d) mutation to E at position 62 (e) mutation to K at position 87 (f) mutation to V at position 208 (g) mutation to D at position 276 (h) mutation to R at position 278 (i) mutation to N at position 279 (j) mutation to I at position 283 (k) mutation to S at position 362 (l) mutation to F at position 371 (m) mutation to E at position 429 (n) deletion of residues 432 to 437 (o) mutation to I at position 455 (p) mutation to I at position 467
or any combination thereof.
7 . A non-naturally occurring protein comprising an eOD variant, wherein the eOD variant is involved in glycan masking, wherein the eOD variant is selected from the group consisting of:
(a) “VD(−)” mutations N276D and N463D
(b) eOD_g2
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIA N C S IAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(c) eOD_g3
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQ N A S TVVSTQ
LLLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIAS
KLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(d) eOD_g4
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAG N V T STQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(e) eOD_g5
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LRE N F S NNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(f) eOD_g6
DTITLPC N P S PPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(g) eOD_g7
DTITLPCR N A T PPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQ
LLLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIAS
KLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(h) eOD_g8
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCG N E T FYCNSTQLFNSTWFNSTWS
(i) eOD_g3-6-8
DTITLPC N P S PPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIARCQ N A S TVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCG N E T FYCNSTQLFNSTWFNSTWS
(j) eOD_g2-6-8
DTITLPC N P S PPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIA N C S IAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCG N E T FYCNSTQLFNSTWFNSTWS
(k) eOD_g2-4-6-8
DTITLPC N P S PPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIA N C S IAG N V T STQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCG N E T FYCNSTQLFNSTWFNSTWS
(l) eOD_g2-5-6-8
DTITLPC N P S PPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIA N C S IAGTVVSTQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LRE N F S NNKTIIFKQSSGGDPEIVTHSFNCG N E T FYCNSTQLFNSTWFNSTWS
(m) eOD_g2-4-5-6-8
DTITLPC N P S PPPHCSSNITGLILTRDGGNSNNESEIFRPGGGDMRDIA N C S IAG N V T STQL
LLNGSLAEEEVVIRSVNFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LRE N F S NNKTIIFKQSSGGDPEIVTHSFNCG N E T FYCNSTQLFNSTWFNSTWS
or any combination thereof.
8 . A non-naturally occurring protein comprising an eOD variant fused with one or more multimerization domains, wherein the eOD variant is selected from the group consisting of:
(a) eOD_VD(−)_3 mer_1gcm_1
RMKQIEDKIEEILSKIYHIENEIARIKKLIGER GGSGGSGG DTITLPCRPAPPPHCSSNITGL
ILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEEVVIRSVDFTD
NAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGD
PEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(b) eOD_VD(−)_3 mer_1gcm_2
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
G RMKQIEDKIEEILSKIYHIENEIARIKKLIGER
(c) eOD_VD(−)_4 mer_1gcl_1
RMKQIEDKLEEILSKLYHIENELARIKKLLGER GGSGGSGG DTITLPCRPAPPPHC SSNIT
GLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEEVVIRSVDFT
DNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGG
DPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(d) eOD_VD(−)_4 mer_1gcl_2
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
G RMKQIEDKLEEILSKLYHIENELARIKKLLGER
(e) eOD_VD(−)_4mer_2b22_1
MKVKQLEDVVEELLSVNYHLENVVARLICKLVGER SGGSGGSGGG DTITLPCRPAPPPH
CSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEEVVI
RSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIF
KQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(f) eOD_VD(−)_4mer_2b22_2
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
GSGGG MKVKQLEDVVEELLSVNYHLENVVARLKKLVGER
(g) eOD_VD(−)_8 mer_1gcl
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
GSGGG RMKQIEDKLEEILSKLYHIENELARIKKLLGER GGSGGSGGSGGG DTITLPCRP
APPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAE
EEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNN
KTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(h) eOD VD(−)_8 mer_2b22
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
GSGGG MKVKQLEDVVEELLSVNYHLENVVARLKKLVGER GGSGGSGGSGGG DTITLP
CRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGS
LAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQF
GNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(i) eODVD(−)_24 mer_3vcd_1
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
GSGGSGGG MSQAIGILELTSIAAGMELGDAMLKSANVDLLVSKTISPGKFLLMLGGDIG
AIQQAIETGTSQAGELLVDSLVLANIHPSVLPAISGLNSVDKRQAVGIVETWSVAAAISA
ADRAVKGSDVTLVRVHMAFGIGGKAYMVVAGDVSDVALAVTVASSSAGAYGLLVYA
SLIPRPHEAMWRQMVEG
(j) eOD_VD(−)_24 mer_3vcd_2
MSQAIGILELTSIAAGMELGDAMLKSANVDLLVSKTISPGKFLLMLGGDIGAIQQAIETG
TSQAGELLVDSLVLANIHPSVLPAISGLNSVDKRQAVGIVETWSVAAAISAADRAVKGS
DVTLVRVHMAFGIGGKAYMVVAGDVSDVALAVTVASSSAGAYGLLVYASLIPRPHEA
MWRQMVEG GGSGGSGGSGGSGGG DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDES
EIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSV
EINCTGAGHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEF
FYCNSTQLFNSTWFNSTWS
(k) eOD_VD(−)_60 mer_1hqk_1
MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDAIVRHGGREEDITLVRVPGSWEIP
VAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRKPITFGVITADTLE
QAIERAGTKHGNKGWEAALSAIEMANLFKSLR GGSGGSGGSGGSGGG DTITLPCRPAP
PPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAEEE
VVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKVVNNTLKQIASKLREQFGNNKT
IIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(l) eOD_VD(−)_60 mer_1hqk_2
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GGSGGSG
GSGGSGGG MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDAIVRHGGREEDITLV
RVPGSWEIPVAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRKPITF
GVITADTLEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR
(m) eOD_VD(−)_60 mer_1hqk_3
MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDAIVRHGGREEDITLVRVPGSWEIP
VAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRKPITFGVITADTLE
QAIERAGTKHGNKGWEAALSAIEMANLFKSLR GSQYIIKANSKFIGITELSG DTITLPCRP
APPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQLLLNGSLAE
EEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASKLREQFGNN
KTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS
(n) eOD_VD(−)_60 mer_1hqk_4
DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARCQIAGTVVSTQL
LLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAKWNNTLKQIASK
LREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWS GSQYIKA
NSKFIGITELSG MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDAIVRHGGREEDI
TLVRVPGSWEIPVAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRK
PITFGVITADTLEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR
(o) eODVD(−)_180 mer_2eOz
VEYFEKLRSALLDGVNKGRSLLKHLPVTRIEGQSFRVDIIKFEDGVRVVKQEYKPIPLLK
KKFYVGIRELNDGTYDVSIATKAGELLVKDEESLVIREILSTEGIKKMKLSSWDNPEEAL
NDLMNALQEASDASAGPFGLIINPKRYAKLLKIYEKSGKMLVEVLKEIFRGGIIVTLNIDE
NKVIIFANTPAVLDVVVGQDVTLQELGPEGDDVAFLVSEAIGIRIKNPEAIVVLE GGSGG
SGGSGGSGGG DTITLPCRPAPPPHCSSNITGLILTRDGGNSNDESEIFRPGGGDMRDIARC
QIAGTVVSTQLLLNGSLAEEEVVIRSVDFTDNAKSICVQLNTSVEINCTGAGHCNISRAK
WNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFN
STWS
or any combination thereof.
9 . A protein having at least 90% homology or identity with the sequence of the protein of claim 1 .
10 . A protein having at least 95% homology or identity with the sequence of the protein of any one of claim 1 .
11 . A nucleic acid encoding the protein of claim 1 .
12 . A nucleic acid having at least 90% homology or identity with the sequence of the nucleic acid of claim 11 .
13 . A nucleic acid having at least 95% homology or identity with the sequence of the nucleic acid of claim 11 .
14 . A method for eliciting an immune response comprising systemically administering to an animal in need thereof an effective amount of the protein of claim 1 .
15 . The method of claim 14 , wherein the animal is a mammal.
16 . The method of claim 15 , wherein the mammal is a human.
17 . A non-naturally occurring protein comprising a HIV Env-based construct having improved binding to a germline VH1-2 antibody comprising one or more of the mutations or modifications selected from the group consisting of:
a) removing a glycosylation site at position 276 in any HIV Env construct from any strain b) mutation to D at position 47 c) mutation to H at position 61 d) mutation to E at position 62 e) mutation to K at position 87 f) mutation to V at position 208 g) mutation to D at position 276 h) mutation to R at position 278 i) mutation to N at position 279 j) mutation to I at position 283 k) mutation to S at position 362 l) mutation to F at position 371 m) mutation to E at position 429 n) deletion of residues 432 to 437 o) mutation to I at position 455 p) mutation to I at position 467 or any combination thereof.
18 . A non-naturally occurring protein comprising any HIV Env-based construct or sequence having improved binding to a germline VH 1-2 antibody comprising one or more of the mutations or modifications selected from the group consisting of:
(a) removing a glycosylation site at position 276 in any HIV Env construct from any strain (b) E47D (c) Y61H (d) D62E (e) E87K (f) 1208V (g) N276D (h) A278R or T278R (i) D279N (j) T283I (k) Replacement of RPNNGGSGSGGDIRQA with GAG (l) K362S (m) 1371F (n) K429E (o) Deletion of residues 432-437 (RAMYAP) (p) T455I (q) V467I
or any combination thereof.
19 . A non-naturally occurring protein comprising any HIV Env-based construct or sequence having improved binding to a germline VH1-2 antibody comprising a deletion of the glycosylation site at position 276 and/or deletion of glycosylation sites on a V5 loop at positions 460, 461, 462, or 463.Join the waitlist — get patent alerts
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