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US 5,688,914 AGranted
Composition containing a B epitope of the envelope glycoprotein of a retrovirus and a T epitope of another distinct protein of this retrovirus
AssigneesInstitut Pasteur, Universite Pierre et Marie Curie (Paris VI)
InventorsMarc Girard, Jean-Claude Gluckman, El Mustapha Bahraoui
Life of this patent
Estimating the term…
Abstract
Compositions comprise one or more B epitopes of the envelope glycoprotein of a retrovirus and one or more T epitopes of the envelope glycoprotein from a distinct retrovirus, or a T epitope from a different protein of the same retrovirus as the B epitope. In particular, the retrovirus is a human immunodeficiency virus (HIV) or a simian immunodeficiency virus (SIV), human T-cell lymphotropic virus type 1 (HTLVI), or human T-cell lymphotropic virus type II (HTLVII).
Claims21
A hybrid molecule of
- (a) at least one peptide having a B epitope of env glycoprotein, which is a major neutralization epitope, of a virus selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIV), human T-cell lymphotropic virus 1 (HTLVI), and human T-cell lymphotropic virus type II (HTLV-II), wherein said peptide has at least one sequence selected from the group consisting of:
- (1) NTRKR IRIQRGPGRA FVTIGK-IGN;
- (2) NTRKK IRIQRGPGRA FVTIGK-IGN;
- (3) NTRGS IRIQRGPGRA FVTIGK-IGN;
- (4) NTRKS IYI--GPGRA FHTTGRIIGD;
- (5) NVRRS LSI--GPGRA FRTRE-IIGI;
- (6) NTRRG IHF--GPGQA LYTTGIV-GD;
- (7) NTRQR TPI--GLGQS LYTTRSR-SI;
- (8) NTRKS ITK--GPGRV IYATGQIIGD;
- (9) NTRKR ITM--GPGRV YYTTGQIIGD;
- (10) DKRQS TPI--GLGQA LYTTRGRTKI;
- (11) DKKR QSIRIGPGKV FYAKGG---I;
- (12) NTKKG IAI--GPGRT LYAREKIIGD;
- (13) HTRKR VTL--GPGRV WYTTGEILGN;
- (14) NTRRG SHF--GPGQA LYTTGIVGDI;
- (15) KITSRQQTPI--GLQA LYTTRIKGDI;
- (16) NVRRR HIHI-GPGRA FYTGEIRNI;
- (17) NTRQS TPI--GLGQA LYTTRTKSI;
- (8) NTTRS IHI--GPGRA FYATGDIIGTI;
- (19) NKRKR IHI--GPGRA FYTTKNIIGDI;
- (20) TRPNNNTRKR IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (21) TRPNN TRKS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (22) TRPNNNTRKK IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (23) TRPNNNTRGS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (24) TRPNNNTRKS IYI-GPGRA FHTTGRIIGD -IRKAH;
- (25) TRPYNNVRRS LSI--GPGRA FRTRE-IIGI IRQAH;
- (26) TRPGNNTRRG IHF--GPGQA LYTTGIV-GD -IRRAY;
- (27) ARPYQNTRQR TPI--GLGQS LYTTRSR-SI -IGQAH;
- (28) TRPNNNTRKS ITK-GPGRV IYATGQIIGD -IRKAH;
- (29) TRPNNNTRKR ITM--GPGRV YYTTGQIIGD -IRRAH;
- (30) TRPGSDKRQS TPI--GLGQA LYTTRGRTKI -IGQAH;
- (31) TRPGSDKKIT QSIRIGPGKV FYAKGG---I -TGQAH;
- and
- (32) TRPNNNTKKG IAI--GPGRT LYAREKIIGD -IRQAH;
- and
- (b) at least one peptide having a T epitope, wherein said peptide has at least one sequence of nef protein of HIV-1 BRU selected from the group consisting of:
- (1) GMDDP EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (2) CYKLV PVEPD KVEEA NKGEN TSLLH PVSLH GMDDP;
- (3) EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (4) DSRLA FHHVA RELHP EYFKN C;
- (5) CGYFP DWQNY TPGPG VRYPL TFGWC YKLVP VEPDK;
- (6) VEEAN KGENT SLLHP V;
- and
- (7) CKGGL EGLIH SQRRQ DILDL WIYHT QGYFP D.
41 more elements
A nucleotide sequence encoding an amino acid sequence for a B epitope, which is a major neutralization epitope, of env glycoprotein of a virus selected from the group consisting of a human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIV), human T-cell lymphotropic virus type 1 (HTLV-I), and human T-cell lymphotropic virus type II (HTLV-II), wherein said B epitope is selected from the group consisting of:
- (1) NTRKR IRIQRGPGRA FVTIGK-IGN;
- (2) NTRKK IRIQRGPGRA FVTIGK-IGN;
- (3) NTRGS IRIQRGPGRA FVTIGK-IGN;
- (4) NTRKS IYI--GPGRA FHTTGRIIGD;
- (5) NVRRS LSI--GPGRA FRTRE-IIGI;
- (6) NTRRG IHF--GPGQA LYTTGIV-GD;
- (7) NTRQR TPI--GLGQS LYTTRSR-SI;
- (8) NTRKS ITK--GPGRV IYATGQIIGD;
- (9) NTRKR ITM--GPGRV YYTTGQIIGD;
- (10) DKRQS TPI--GLGQA LYTTRGRTKI;
- (11) DKKIR QSIRIGPGKV FYAKGG---I;
- (12) NTKKG IAI--GPGRT LYAREKIIGD;
- (13) HTRKR VTL--GPGRV WYTTGEILGN;
- (14) NTRRG SHF--GPGQA LYTTGIVGDI;
- (15) KITSRQQTPI--GLQA LYTTRIKGDI;
- (16) NVRRR HIHI-GPGRA FYTGEIRNI;
- (17) NTRQS TPI--GLGQA LYTTRTKSI;
- (18) NTTRS IHI--GPGRA FYATGDIIGTI;
- (19) NKRKR IHI--GPGRA FYTTKNIIGDI;
- (20) TRPNNNTRKR IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (21) TRPNN TRKS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (22) TRPNNNTRKK IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (23) TRPNNNTRGS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (24) TRPNNNTRKS IYI--GPGRA FHTTGRIIGD -IRKAH;
- (25) TRPYNNVRRS LSI--GPGRA FRTRE-IIGI IRQAH;
- (26) TRPGNNTRRG IHF--GPGQA LYTTGIV-GD -IRRAY;
- (27) ARPYQNTRQR TPI--GLGQS LYTTRSR-SI -IGQAH;
- (28) TRPNNNTRKS ITK--GPGRV IYATGQIIGD -IRKAH;
- (29) TRPNNNTRKR ITM--GPGRV YYTTGQIIGD -IRRAH;
- (30) TRPGSDKRQS TPI--GLGQA LYTTRGRTKI -IGQAH;
- (31) TRPGSDKKIT QSIRIGPGKV FYAKGG---I -TGQAH;
- and
- (32) TRPNNNTKKG IAI--GPGRT LYAREKIIGD -IRQAH.
30 more elements
A nucleotide sequence encoding an amino acid sequence for a T epitope of nef protein of HIV-1 BRU, wherein said T epitope is selected from the group consisting of:
- (1) GMDDP EREVL EWRFD SRLAF HHVAR ELKPE YFKNC;
- (2) CYKLV PVEPD KVEEA NKGEN TSKKH PVSLH GMDDP;
- (3) EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (4) DSRLA FHHVA RELHP EYFKN C;
- (5) CGYFP DWQNY TPGPG VRYPL TFGWC YKLVP VEPDK;
- and
- (6) VEEAN KGENT SLLHP V.
4 more elements
An immunogenic hybrid molecule having
- (a) at least one B epitope of env glycoprotein, which is a major neutralization epitope, of a virus selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIV), human T-cell lymphotropic virus type 1 (HTLVI), and human T-cell lymphotropic virus type II (HTLVII), said at least one B epitope is selected from the group consisting of:
- (1) NTRKR IRIQRGPGRA FVTIGK-IGN;
- (2) NTRKS IRIQRGPGRA FVTIGK-IGN;
- (3) NTRKK IRIQRGPGRA FVTIGK-IGN;
- (4) NTRGS IRIQRGPGRA FVTIGK-IGN;
- (5) NTRKS IYI--GPGRA FHTTGRIIGD;
- (6) NVRRS LSI--GPGRA FRTRE-IIGI;
- (7) NTRRG IHF--GPGQA LYTTGIV-GD;
- (8) NTRQR TPI--GLGQS LYTTRSR-SI;
- (9) NTRKS ITK--GPGRV IYATGQIIGD;
- (10) NTRKR ITM--GPGRV YYTTGQIIGD;
- (11) DKRQS TPI--GLGQA LYTTRGRTKI;
- (12) DKKIR QSIRIGPGKV FYAKGG---I;
- (13) NTKKG IAI--GPGRT LYAREKIIGD;
- (14) HTRKR VTL--GPGRV WYTTGEILGN;
- (15) NTRRG SHF--GPGQA LYTTGIVGDI;
- (16) KITSRQTPI--GLGQA LYTTRIKGDI;
- (17) NVRRR HIHI-GPGRA FYTGEIRNI;
- (18) NTRQS TPI--GLGQA LYTTRTKSI;
- (19) NTTRS IHI--GPGRA FYATGDIIGTI;
- (20) NKRKR IHI--GPGRA FYTTKNIIGDI;
- (21) TRPNNNTRKR IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (22) TRPNNNTRKS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (23) TRPNNNTRKK IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (24) TRPNNNTRGS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (25) TRPNNNTRKS IYI--GPGRA FHTTGRIIGD -IRKAH;
- (26) TRPYNNVRRS LSI--GPGRA FRTRE-IIGI -IRQAH;
- (27) TRPGNNTRRG IHF--GPGQA LYTTGIV-GD -IRRAY;
- (28) ARPYQNTRQR TPI--GLGQS LYTTRSR-SI -IGQAH;
- (29) TRPNNNTRKS ITK--GPGRV IYATGQIIGD -IRKAH;
- (30) TRPNNNTRKR ITM--GPGRV YYTTGQIIGD -IRRAH;
- (31) TRPGSDKRQS TPI--GLGQA LYTTRGRTKI -IGQAH;
- (32) TRPGSDKKIR QSIRIGPGKV FYAKGG--I -TGQAH;
- and
- (33) TRPNNNTKKG IAI-GPGRT LYAREKIIGD -IRQAH;
- wherein said at least one B epitope is chemically coupled to
- (b) at least one T epitope of nef protein of BIV-1 BRU selected from the group consisting of:
- (1) GMDDP EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (2) CYKLV PVEPD KVEEA NKGEN TSLLH PVSLH GMDDP;
- (3) EREVL EWRFD SRLAF HHVAR ELBPE YFKNC;
- (4) DSRLA FHHVA RELHP EYFKN C;
- (5) CGYFP DWQNY TPGPG VRYPL TFGWC YKLVP VEPDK;
- (6) VEEAN KGENT SLLHP V;
- and
- (7) CKGGL EGLIH SQRRQ DILDL WIYHT QGYFP D;
- wherein said immunogenic hybrid molecule induces in vivo production of antibodies against said virus.
43 more elements
An immunogenic composition comprising a hybrid molecule of
- (a) at least one peptide comprising a B epitope of env glycoprotein, which is a major neutralization epitope, of a virus selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIV), human T-cell lymphotropic virus type 1 (HTLVI), and human T-cell lymphotropic virus type II (HTLV-II), wherein said peptide comprises at least one sequence selected from the group consisting of:
- (1) NTRKR IRIQRGPGRA FVTIGK-IGN;
- (2) NTRKK IRIQRGPGRA FVTIGK-IGN;
- (3) NTRGS IRIQRGPGRA FVTIGK-IGN;
- (4) NTRKS IYI--GPGRA FHTTGRIIGD;
- (5) NVRRS LSI--GPGRA FRTRE-IIGI;
- (6) NTRRG IHF--GPGQA LYTTGIV-GD;
- (7) NTRQR TPI--GLGQS LYTTRSR-SI;
- (8) NTRKS ITK--GPGRV IYATGQIIGD;
- (9) NTRKR ITM--GPGRV YYTTGQIIGD;
- (10) DKRQS TPI--GLGQA LYTTRGRTKI;
- (11) DKKIR QSIRIGPGKV FYAKGG---I;
- (12) NTKKG IAI--GPGRT LYAREKIIGD;
- (13) HTRKR VTL--GPGRV WYTTGEILGN;
- (14) NTRRG SHF--GPGQA LYTTGIVGDI;
- (15) KITSRQQTPI--GLQA LYTTRIKGDI;
- (16) NVRRR HIHI-GPGRA FYTGEIRNI;
- (17) NTRQS TPI--GLGQA LYTTRTKSI;
- (18) NTTRS IHI--GPGRA FYATGDIIGTI;
- (19) NKRKR IHI--GPGRA FYTTKNIIGDI;
- (20) TRPNNNTRKR IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (21) TRPNN TRKS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (22) TRPNNNTRKK IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (23) TRPNNNTRGS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (24) TRPNNNTRKS IYI--GPGRA FHTTGRIIGD -IRKAH;
- (25) TRPYNNVRRS LSI--GPGRA FRTRE-IIGI IRQAH;
- (26) TRPGNNTRRG IHF--GPGQA LYTTGIV-GD -IRRAY;
- (27) ARPYQNTRQR TPI--GLGQS LYTTRSR-SI -IGQAH;
- (28) TRPNNNTRKS ITK--GPGRV IYATGQIIGD -IRKAH;
- (29) TRPNNNTRKR ITM--GPGRV YYTTGQIIGD -IRRAH;
- (30) TRPGSDKRQS TPI--GLGQA LYTTRGRTKI -IGQAH;
- (31) TRPGSDKKIT QSIRIGPGKV FYAKGG---I -TGQAH;
- and
- (32) TRPNNNTKKG IAI--GPGRT LYAREKIIGD -IRQAH;
- and
- (b) at least one peptide comprising a T epitope, wherein said peptide comprises at least one sequence of nef protein of HIV-1 BRU selected from the group consisting of:
- (1) GMDDP EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (2) CYKLV PVEPD KVEEA NKGEN TSLLH PVSLH GMDDP;
- (3) EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (4) DSRLA FHHVA RELHP EYFKN C;
- (5) CGYFP DWQNY TPGPG VRYPL TFGWC YKLVP VEPDK;
- (6) VEEAN KGENT SLLHP V;
- and
- (7) CKGGL EGLIH SQRRQ DILDL WIYHT QGYFP D.
41 more elements
A method of preparing a hybrid molecule comprising
- coupling at least one peptide comprising a B epitope of env glycoprotein, which is a major neutralization epitope, of a virus selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIV), human T-cell lymphotropic virus type 1 (HTLVI), and human T-cell lymphotropic virus type II (HTLV-II), wherein said peptide comprises at least one sequence selected from the group consisting of:
- (1) NTRKR IRIQRGPGRA FVTIGK-IGN;
- (2) NTRKK IRIQRGPGRA FVTIGK-IGN;
- (3) NTRGS IRIQRGPGRA FVTIGK-IGN;
- (4) NTRKS IYI--GPGRA FHTTGRIIGD;
- (5) NVRRS LSI--GPGRA FRTRE-IIGI;
- (6) NTRRG IHF--GPGQA LYTTGIV-GD;
- (7) NTRQR TPI--GLGQS LYTTRSR-SI;
- (8) NTRKS ITK--GPGRV IYATGQIIGD;
- (9) NTRKR ITM--GPGRV YYTTGQIIGD;
- (10) DKRQS TPI--GLGQA LYTTRGRTKI;
- (11) DKKIR QSIRIGPGKV FYAKGG---I;
- (12) NTKKG IAI--GPGRT LYAREKIIGD;
- (13) HTRKR VTL--GPGRV WYTTGEILGN;
- (14) NTRRG SHF--GPGQA LYTTGIVGDI;
- (15) KITSRQQTPI--GLQA LYTTRIKGDI;
- (16) NVRRR HIHI-GPGRA FYTGEIRNI;
- (17) NTRQS TPI--GLGQA LYTTRTKSI;
- (18) NTTRS IHI--GPGRA FYATGDIIGTI;
- (19) NKRKR IHI--GPGRA FYTTKNIIGDI;
- (20) TRPNNNTRKR IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (21) TRPNN TRKS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (22) TRPNNNTRKK IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (23) TRPNNNTRGS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (24) TRPNNNTRKS IYI--GPGRA FHTTGRIIGD -IRKAH;
- (25) TRPYNNVRRS LSI--GPGRA FRTRE-IIGI IRQAH;
- (26) TRPGNNTRRG IHF--GPGQA LYTTGIV-GD -IRRAY;
- (27) ARPYQNTRQR TPI--GLGQS LYTTRSR-SI -IGQAH;
- (28) TRPNNNTRKS ITK--GPGRV IYATGQIIGD -IRKAH;
- (29) TRPNNNTRKR ITM--GPGRV YYTTGQIIGD -IRRAH;
- (30) TRPGSDKRQS TPI--GLGQA LYTTRGRTKI -IGQAH;
- (31) TRPGSDKKIT QSIRIGPGKV FYAKGG---I -TGQAH;
- and
- (32) TRPNNNTKKG IAI--GPGRT LYAREKIIGD -IRQAH;
- with at least one peptide comprising a T epitope, wherein said peptide comprises at least one sequence of nef protein of HIV-1 BRU selected from the group consisting of:
- (1) GMDDP EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (2) CYKLV PVEPD KVEEA NKGEN TSLLH PVSLH GMDDP;
- (3) EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (4) DSRLA FHHVA RELHP EYFKN C;
- (5) CGYFP DWQNY TPGPG VRYPL TFGWC YKLVP VEPDK;
- (6) VEEAN KGENT SLLHP V;
- and
- (7) CKGGL EGLIH SQRRQ DILDL WIYHT QGYFP D.
40 more elements
A method of preparing a hybrid molecule comprising the steps of transforming a host cell with a nucleotide sequence coding for a hybrid molecule of
- (a) at least one peptide comprising a B epitope of env glycoprotein, which is a major neutralization epitope, of a virus selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIV), human T-cell lymphotropic virus type 1 (HTLVI), and human T-cell lymphotropic virus type II (HTLV-II), wherein said peptide comprises at least one sequence selected from the group consisting of:
- (1) NTRKR IRIQRGPGRA FVTIGK-IGN;
- (2) NTRKK IRIQRGPGRA FVTIGK-IGN;
- (3) NTRGS IRIQRGPGRA FVTIGK-IGN;
- (4) NTRKS IYI--GPGRA FHTTGRIIGD;
- (5) NVRRS LSI--GPGRA FRTRE-IIGI;
- (6) NTRRG IHF--GPGQA LYTTGIV-GD;
- (7) NTRQR TPI--GLGQS LYTTRSR-SI;
- (8) NTRKS ITK--GPGRV IYATGQIIGD;
- (9) NTRKR ITM--GPGRV YYTTGQIIGD;
- (10) DKRQS TPI--GLGQA LYTTRGRTKI;
- (11) DKKIR QSIRIGPGKV FYAKGG---I;
- (12) NTKKG IAI--GPGRT LYAREKIIGD;
- (13) HTRKR VTL--GPGRV WYTTGEILGN;
- (14) NTRRG SHF--GPGQA LYTTGIVGDI;
- (15) KITSRQQTPI--GLQA LYTTRIKGDI;
- (16) NVRRR HIHI--GPGRA FYTGEIRNI;
- (17) NTRQS TPI--GLGQA LYTTRTKSI;
- (18) NTTRS IHI--GPGRA FYATGDIIGTI;
- (19) NKRKR IHI--GPGRA FYTTKNIIGDI;
- (20) TRPNNNTRKR IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (21) TRPNN TRKS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (22) TRPNNNTRKK IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (23) TRPNNNTRGS IRIQRGPGRA FVTIGK-IGN M-RQAH;
- (24) TRPNNNTRKS IYI--GPGRA FHTTGRIIGD -IRKAH;
- (25) TRPYNNVRRS LSI--GPGRA FRTRE-IIGI IRQAH;
- (26) TRPGNNTRRG IHF--GPGQA LYTTGIV-GD -IRRAY;
- (27) ARPYQNTRQR TPI--GLGQS LYTTRSR-SI -IGQAH;
- (28) TRPNNNTRKS ITK--GPGRV IYATGQIIGD -IRKAH;
- (29) TRPNNNTRKR ITM--GPGRV YYTTGQIIGD -IRRAH;
- (30) TRPGSDKRQS TPI--GLGQA LYTTRGRTKI -IGQAH;
- (31) TRPGSDKKIT QSIRIGPGKV FYAKGG---I -TGQAH;
- and
- (32) TRPNNNTKKG IAI--GPGRT LYAREKIIGD -IRQAH;
- and
- (b) at least one peptide comprising a T epitope, wherein said peptide comprises at least one sequence of nef protein of HIV-1 BRU selected from the group consisting of:
- (1) GMDDP EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (2) CYKLV PVEPD KVEEA NKGEN TSLLH PVSLH GMDDP;
- (3) EREVL EWRFD SRLAF HHVAR ELHPE YFKNC;
- (4) DSRLA FHHVA RELHP EYFKN C;
- (5) CGYFP DWQNY TPGPG VRYPL TFGWC YKLVP VEPDK;
- (6) VEEAN KGENT SLLHP V;
- and
- (7) CKGGL EGLIH SQRRQ DILDL WIYHT QGYFP D;
- detecting the presence of the expressed hybrid molecule;
- and isolating said hybrid molecule.
43 more elements
Dependencies are inferred from the claim text.