The development of an HIV-1 vaccine has been frustrated in part by
the difficulty of eliciting neutralizing antibodies active against
clinical HIV-1 isolates (3, 4, 6, 14, 28, 29, 41, 42, 57, 76,
79). To date, no defined immunogen has proven better than the
gp120 glycoprotein, which generates primary virus-neutralizing activity
only after an aggressive immunization protocol involving many boosts
(3, 4, 14, 28, 29, 41, 42, 57, 76). Immunization of
specific transgenic mice with mixtures of cells expressing envelope
glycoproteins and receptors has been reported to yield antibodies able
to neutralize a broad range of primary HIV-1 isolates
(37); however, despite extensive efforts, the relevant
immunogen has not been defined and the reproducibility and general
applicability of the results have not been demonstrated. Our results
indicate that soluble, stabilized trimers are more effective than gp120
at eliciting antibodies that neutralize HIV-1. Such trimers may
represent more faithful mimics of the functional envelope glycoprotein
complex, may retain relevant conformations more stably in vivo, and may
present multiple, cross-linked epitopes to responding B lymphocytes.
Our results suggest that the HIV-1 strain from which the soluble,
stabilized trimers are derived can influence the elicitation of primary
virus-neutralizing activity. The trimers derived from the primary YU2
isolate generated better neutralizing responses against clinical HIV-1
isolates than did trimers from a TCLA virus. This suggests that some
primary virus trimers can elicit antibodies that recognize structures
common to several primary isolates and at least one TCLA HIV-1 isolate.
The neutralizing antibodies generated by the TCLA virus trimer,
although quite potent against the homologous TCLA isolate, were not
generally active against the primary isolates tested. Despite the
similarity of recognition of the YU2 and HXBc2 trimers by antibodies
directed against conserved epitopes (85), the neutralizing
antibody response to the TCLA virus trimer appears to be dominated by
reactivity with more strain-specific elements. The properties that
render soluble, stabilized trimers from certain HIV-1 strains more
effective as immunogens merit further investigation.
Although soluble, stabilized trimers appeared to elicit some
qualitatively desirable neutralizing antibody responses, efforts to
improve the titer and breadth of these responses are clearly merited.
The titers of primary-virus-neutralizing antibodies observed in our
immunized mice were low. Furthermore, the breadth of neutralization was
limited to a subset of clade B viruses. These limitations may reflect
intrinsic immunogenic properties of the HIV-1 envelope glycoprotein
complexes. Alternatively, the soluble stabilized trimers may
imperfectly mimic the functional virion envelope glycoprotein spikes.
Further modifications of the immunogens and methods of antigen
presentation to the immune system may lead to improved neutralizing
antibody responses.
We thank E. Myers for assistance with animal handling. We also
thank Y. McLaughlin and S. Farnum for manuscript preparation.
This work was supported by NIH grants AI24755, AI31783, and AI39420 to
J.S. and NIH CFAR grant AI28691. We also acknowledge the support of the
G. Harold and Leila Mathers Foundation, the Friends 10, Douglas and
Judith Krupp, and the late William F. McCarty-Cooper.
| 1.
|
Alkhatib, G.,
C. Combadiere,
C. C. Broder,
Y. Feng,
P. E. Kennedy,
P. M. Murphy, and E. A. Berger.
1996.
CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
Science
272:1955-1958[Abstract].
|
| 2.
|
Allan, J. S.,
J. E. Coligan,
F. Barin,
J. Sodroski,
C. A. Rosen,
W. A. Haseltine,
T.-H. Lee, and M. Essex.
1985.
Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III.
Science
228:1091-1094[Abstract/Free Full Text].
|
| 3.
|
Barnett, S. W.,
S. Rajasekar,
H. Legg,
B. Doe,
D. H. Fuller,
J. R. Haynes,
C. M. Walker, and K. S. Steimer.
1997.
Vaccination with HIV-1 gp120 DNA induces immune responses that are boosted by a recombinant gp120 protein subunit.
Vaccine
15:869-873[CrossRef][Medline].
|
| 4.
|
Belshe, R. B.,
G. J. Gorse,
M. J. Mulligan,
T. G. Evans,
M. C. Keefer,
J.-L. Excler,
A. M. Duliege,
J. Tartaglia,
W. I. Cox,
J. McNamara,
K.-L. Hwang,
A. Bradney,
D. C. Montefiori, and K. J. Weinhold.
1998.
Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers.
AIDS
12:2407-2415[CrossRef][Medline].
|
| 5.
|
Berkower, I.,
G. Smith,
C. Giri, and D. Murphy.
1989.
Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.
J. Exp. Med.
170:1681-1695[Abstract/Free Full Text].
|
| 6.
|
Berman, P. W.,
T. J. Gregory,
L. Riddle,
G. R. Nakamura,
M. A. Champe,
J. P. Porter,
F. M. Wurm,
R. D. Hershberg,
E. K. Cobb, and J. W. Eichberg.
1990.
Protection of chimpanzees from infections by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160.
Nature
345:622-625[CrossRef][Medline].
|
| 7.
|
Binley, J. M.,
R. W. Sanders,
B. Clas,
N. Schuelke,
A. Master,
Y. Guo,
F. Kajumo,
D. J. Anselma,
P. J. Maddon,
W. C. Olson, and J. P. Moore.
2000.
A recombinant immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp 120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure.
J. Virol.
74:627-643[Abstract/Free Full Text].
|
| 8.
|
Bou-Habib, D. C.,
G. Roderiquez,
T. Oravecz,
P. W. Berman,
P. Luzzo, and M. Norcross.
1994.
Cryptic nature of envelope V3 region epitopes protects primary monocytotropic human immunodeficiency virus type 1 from antibody neutralization.
J. Virol.
68:6006-6013[Abstract/Free Full Text].
|
| 9.
|
Broder, C. C.,
P. L. Earl,
D. Long,
S. T. Abedon,
B. Moss, and R. W. Doms.
1994.
Antigenic implications of human immunodeficiency virus type 1 envelope quatemary structure: oligomer-specific and -sensitive monoclonal antibodies.
Proc. Natl. Acad. Sci. USA
91:11699-11703[Abstract/Free Full Text].
|
| 10.
|
Burton, D. R.,
J. Pyati,
R. Koduri,
G. B. Thornton,
L. S. W. Sawyer,
R. M. Hendry,
N. Dunlop,
P. L. Nara,
M. Lamacchia,
E. Garratty,
E. R. Stiehm,
Y. J. Bryson,
J. P. Moore,
D. D. Ho, and C. F. Barbas, III.
1994.
Efficient neutralization of primary isolates of HIV-1 by a recombinant monoclonal antibody.
Science
266:1024-1027[Abstract/Free Full Text].
|
| 11.
|
Chan, D. C.,
D. Fass,
J. M. Berger, and P. S. Kim.
1997.
Core structure of gp41 from the HIV envelope glycoprotein.
Cell
89:263-273[CrossRef][Medline].
|
| 12.
|
Chan, D. C., and P. S. Kim.
1998.
HIV entry and its inhibition.
Cell
93:681-684[CrossRef][Medline].
|
| 13.
|
Choe, H.,
M. Farzan,
Y. Sun,
N. Sullivan,
B. Rollins,
P. D. Ponath,
L. Wu,
C. R. Mackay,
G. LaRosa,
W. Newman,
N. Gerard,
C. Gerard, and J. Sodroski.
1996.
The -chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.
Cell
85:1135-1148[CrossRef][Medline].
|
| 14.
|
Connor, R. I.,
B. T. Korber,
B. S. Graham,
B. H. Hahn,
D. D. Ho,
R. D. Walker,
A. U. Neumann,
S. H. Vermund,
J. Mestecky,
S. Jackson,
E. Fenamore,
Y. Cao,
F. Gao,
S. Kalam,
K. J. Kunstman,
D. McDonald,
N. McWilliams,
A. Trkola,
J. P. Moore, and S. M. Wolinsky.
1998.
Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant subunit vaccines.
J. Virol.
72:1552-1576[Abstract/Free Full Text].
|
| 15.
|
Daar, E. S.,
X. L. Li,
T. Moudgil, and D. D. Ho.
1990.
High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates.
Proc. Natl. Acad. Sci. USA
87:6574-6578[Abstract/Free Full Text].
|
| 16.
|
Dalgleish, A. G.,
P. C. Beverley,
P. R. Clapham,
D. H. Crawford,
M. F. Greaves, and R. A. Weiss.
1984.
The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.
Nature
312:763-767[CrossRef][Medline].
|
| 17.
|
Deng, H.,
R. Liu,
W. Ellmeier,
S. Choe,
D. Unutmaz,
M. Burkhart,
P. Di Marzio,
S. Marmon,
R. E. Sutton,
C. M. Hill,
C. B. Davis,
S. C. Peiper,
T. J. Schall,
D. R. Littman, and N. R. Landau.
1996.
Identification of a major co-receptor for primary isolates of HIV-1.
Nature
381:661-666[CrossRef][Medline].
|
| 18.
|
Ditzel, H. J.,
J. M. Binley,
J. P. Moore,
J. Sodroski,
N. Sullivan,
L. Sawyer,
R. M. Hendry,
W. Yang,
C. F. Barbas III, and D. R. Burton.
1995.
Neutralizing recombinant human antibodies to a conformational V2- and CD4-binding site-sensitive epitope of HIV-1 gp120 isolated by using an epitope-masking procedure.
J. Immunol.
154:893-906[Abstract].
|
| 19.
|
Doranz, B. J.,
J. Rucker,
Y. Yi,
R. J. Smyth,
M. Samson,
S. C. Peiper,
M. Parmentier,
R. G. Collman, and R. W. Doms.
1996.
A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors.
Cell
85:1149-1158[CrossRef][Medline].
|
| 20.
|
Dragic, T.,
V. Litwin,
G. P. Allaway,
S. R. Martin,
Y. Huang,
K. A. Nagashima,
C. Cayanan,
P. J. Maddon,
R. A. Koup,
J. P. Moore, and W. A. Paxton.
1996.
HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC- CKR-5.
Nature
381:667-673[CrossRef][Medline].
|
| 21.
|
Earl, P. L.,
C. C. Broder,
D. Long,
S. A. Lee,
J. Peterson,
S. Chakrabarti,
R. W. Doms, and B. Moss.
1994.
Native oligomeric human immunodeficiency virus type 1 envelope glycoprotein elicits diverse monoclonal antibody reactivities.
J. Virol.
68:3015-3026[Abstract/Free Full Text].
|
| 22.
|
Earl, P. L.,
R. W. Doms, and B. Moss.
1990.
Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein.
Proc. Natl. Acad. Sci. USA
87:648-652[Abstract/Free Full Text].
|
| 23.
|
Earl, P. L.,
B. Moss, and R. W. Doms.
1991.
Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein.
J. Virol.
65:2047-2055[Abstract/Free Full Text].
|
| 24.
|
Farzan, M.,
H. Choe,
E. Desjardins,
Y. Sun,
J. Kuhn,
J. Cao,
D. Archambault,
P. Kolchinsky,
M. Koch,
R. Wyatt, and J. Sodroski.
1998.
Stabilization of human immunodeficiency virus type 1 envelope glycoprotein trimers by disulfide bonds introduced into the gp41 glycoprotein ectodomain.
J. Virol.
72:7620-7625[Abstract/Free Full Text].
|
| 25.
|
Feng, Y.,
C. C. Broder,
P. E. Kennedy, and E. A. Berger.
1996.
HIV-1 entry cofactor: functional cDNA cloning of a seven- transmembrane, G protein-coupled receptor.
Science
272:872-877[Abstract].
|
| 26.
|
Gelderblom, H. R.,
H. Reupke, and G. Pauli.
1985.
Loss of envelope antigens of HTLV-III/LAV, a factor in AIDS pathogenesis?
Lancet
ii:1016-1017.
|
| 27.
|
Gorny, M. K.,
J. P. Moore,
A. J. Conley,
S. Karwowska,
J. Sodroski,
C. Williams,
S. Burda,
L. J. Boots, and S. Zolla-Pazner.
1994.
Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1.
J. Virol.
68:8312-8320[Abstract/Free Full Text].
|
| 28.
|
Graham, B. S.,
M. J. McElrah,
R. I. Conner,
D. H. Schwartz,
G. J. Gorse,
M. C. Keefer,
M. J. Mulligan,
T. J. Mathews,
S. W. Wolinsky,
D. C. Montefiori,
S. H. Vermund,
J. S. Lambert,
L. Corey,
R. B. Belshe,
R. Dolin,
P. F. Wrightt,
B. T. Korber,
M. C. Wolff, and P. E. Fast.
1998.
Analysis of intercurrent human immunodeficiency virus type 1 infections in phase I and II trials of current AIDS vaccines.
J. Infect. Dis.
177:310-319[Medline].
|
| 29.
|
Haigwood, N. L.,
P. Nara,
E. Brooks,
G. Van Nest,
G. Ott,
K. Higgins,
N. Dunlop,
C. Scandella,
J. Eichberg, and K. Steimer.
1992.
Native but not denatured recombinant human immunodeficiency type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons.
J. Virol.
66:172-182[Abstract/Free Full Text].
|
| 30.
|
Harbury, P. B.,
T. Zhang,
P. S. Kim, and T. Alber.
1993.
A switch between two-three-, and four-stranded coiled coils in GCN4 leucine zipper mutants.
Science
262:1401-1407[Abstract/Free Full Text].
|
| 31.
|
Ho, D. D.,
J. McKeating,
X. L. Li,
T. Moudgil,
E. Daar,
N. C. Sun, and J. Robinson.
1991.
Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody.
J. Virol.
65:489-493[Abstract/Free Full Text].
|
| 32.
|
Karwowska, S.,
M. Gorny,
A. Buchbinder,
V. Gianakakos,
C. Williams,
T. Fuerst, and S. Zolla-Pazner.
1992.
Production of human monoclonal antibodies specific for conformational and linear non-V3 epitopes of gp120.
AIDS Res. Hum. Retroviruses
8:1099-1106[Medline].
|
| 33.
|
Klaniecki, J.,
T. Dykers,
B. Travis,
R. Schmitt,
M. Wain,
A. Watson,
P. Sridhar,
J. McClure,
B. Morein, and J. T. Ulrich.
1991.
Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus.
AIDS Res. Hum. Retroviruses
7:791-798[Medline].
|
| 34.
|
Klatzmann, D.,
E. Chamoagne,
S. Chamaret,
J. Gruest,
D. Guetard,
T. Hercend,
J. C. Gluckman, and L. Montagnier.
1984.
T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV.
Nature
312:767-768[CrossRef][Medline].
|
| 35.
|
Kwong, P. D.,
R. Wyatt,
J. Robinson,
R. W. Sweet,
J. Sodroski, and W. A. Henderickson.
1998.
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.
Nature
393:648-659[CrossRef][Medline].
|
| 36.
|
Kwong, P. D.,
R. Wyatt,
E. Desjardins,
J. Robinson,
J. Culp,
B. D. Hellmig,
R. W. Sweet,
J. Sodroski, and W. Hendrickson.
1999.
Probability analysis of variational crystallization and its application to gp120, the exterior envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1).
J. Biol. Chem.
274:4115-4123[Abstract/Free Full Text].
|
| 37.
|
LaCasse, R. A.,
K. E. Follis,
M. Trahey,
J. Scarborough,
D. R. Littman, and J. H. Nunberg.
1999.
Fusion-competent vaccines: broad neutralization of primary isolates of HIV.
Science
283:357-362[Abstract/Free Full Text].
|
| 38.
|
Li, Y.,
J. Kappes,
J. Conway,
R. W. Price,
G. Shaw, and B. Hahn.
1991.
Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes.
J. Virol.
65:3973-3985[Abstract/Free Full Text].
|
| 39.
|
Lu, M.,
S. Blackow, and P. Kim.
1995.
A trimeric structural domain of the HIV-1 transmembrane glycoprotein.
Nat. Struct. Biol.
2:1075-1082[CrossRef][Medline].
|
| 40.
|
Mascola, J. R.,
J. Louwagie,
F. McCutchan,
C. Fischer,
P. Hegerick,
K. Wagner,
A. K. Fowler,
J. G. McNeil, and D. S. Burke.
1994.
Two antigenically distinct subtypes of human immunodeficiency virus type 1: viral genotype predicts neutralization serotype.
J. Infect. Dis.
169:48-54[Medline].
|
| 41.
|
Mascola, J. R.,
S. W. Snyder,
O. S. Weislow,
S. M. Belay,
R. B. Belshe,
D. H. Schwartz,
M. L. Clements,
R. Dolin,
B. S. Graham,
G. J. Gorse,
M. C. Keefer,
M. J. McElrath,
M. C. Walker,
K. F. Wagner,
J. G. McNeil,
F. E. McCutchan, and D. S. Burke.
1996.
Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group.
J. Infect. Dis.
173:340-348[Medline].
|
| 42.
|
Matthews, T. J.
1994.
Dilemma of neutralization resistance of HIV-1 field isolates and vaccine development.
AIDS Res. Hum. Retroviruses
10:631-632[Medline].
|
| 43.
|
McDougal, J. S.,
J. K. Nicholson,
G. D. Cross,
S. P. Cort,
M. S. Kennedy, and A. C. Mawle.
1986.
Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry.
J. Immunol.
137:2937-2944[Abstract].
|
| 44.
|
McKeating, J. A.,
A. McKnight, and J. P. Moore.
1991.
Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization.
J. Virol.
65:852-860[Abstract/Free Full Text].
|
| 45.
|
McKeating, J.,
C. Shotton,
J. Cordell,
S. Graham,
P. Balfe,
N. Sullivan,
M. Charles,
M. Page,
A. Bolmstedt,
S. Olofsson,
S. Kayman,
Z. Wu,
A. Pinter,
C. Dean,
J. Sodroski, and R. Weiss.
1993.
Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120.
J. Virol.
67:4932-4944[Abstract/Free Full Text].
|
| 46.
|
Moore, J. P.,
J. McKeating,
Y. Huang,
A. Ashkenazi, and D. D. Ho.
1992.
Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive ones.
J. Virol.
66:235-243[Abstract/Free Full Text].
|
| 47.
|
Moore, J. P.,
Q. J. Sattentau,
H. Yoshiyama,
M. Thali,
M. Charles,
N. Sullivan,
S. W. Poon,
M. S. Fung,
F. Traincard,
M. Pinkus,
G. Robey,
J. E. Robinson,
D. D. Ho, and J. Sodroski.
1993.
Probing the structure of the V2 domain of human immunodeficiency virus type 1 surface glycoprotein gp120 with a panel of eight monoclonal antibodies: human immune response to the V1 and V2 domains.
J. Virol.
67:6136-6151[Abstract/Free Full Text].
|
| 48.
|
Moore, J. P., and D. D. Ho.
1995.
HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells.
AIDS
9(Suppl. A):S117-S136.
|
| 49.
|
Moore, J. P.,
A. Trkola,
B. Korber,
L. Boots,
J. Kessler,
F. E. McCutchan,
J. Mascola,
D. D. Ho,
J. Robinson, and A. J. Conley.
1995.
A human monoclonal antibody to a complex epitope in the V3 region of gp120 of human immunodeficiency virus type 1 has broad reactivity within and outside clade B.
J. Virol.
69:122-130[Abstract].
|
| 50.
|
Moore, J. P.,
Y. Cao,
L. Qing,
Q. J. Sattentau,
J. Pyati,
R. Koduri,
J. Robinson,
C. F. Barbas III,
D. R. Burton, and D. D. Ho.
1995.
Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120.
J. Virol.
69:101-109[Abstract].
|
| 51.
|
O'Brien, W. A.,
S. H. Mao,
Y. Cao, and J. P. Moore.
1994.
Macrophage-tropic and T-cell line-adapted chimeric strains of human immunodeficiency virus type 1 differ in their susceptibilities to neutralization by soluble CD4 at different temperatures.
J. Virol.
68:5264-5269[Abstract/Free Full Text].
|
| 52.
|
Ohno, T.,
M. Terada,
Y. Yoneda,
K. W. Shea,
R. F. Chambers,
D. M. Stroka,
M. Nakamura, and D. W. Kufe.
1991.
A broadly neutralizing monoclonal antibody that recognizes the V3 region of human immunodeficiency virus type 1 glycoprotein gp120.
Proc. Natl. Acad. Sci. USA
88:10726-10729[Abstract/Free Full Text].
|
| 53.
|
Posner, M. R.,
T. Hideshima,
T. Cannon,
M. Mukherjee,
K. Mayer, and R. Byrn.
1991.
An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection.
J. Immunol.
146:4325-4332[Abstract].
|
| 54.
|
Profy, A. T.,
P. Salinas,
L. Eckler,
N. Dunlop,
P. Nara, and S. D. Putney.
1990.
Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individuals.
J. Immunol.
144:4641-4647[Abstract].
|
| 55.
|
Rao, Z.,
A. S. Belyaev,
E. Fry,
P. Roy,
I. M. Jones, and D. I. Stuart.
1995.
Crystal structure of SIV matrix antigen and implications for virus assembly.
Nature
378:743-74[CrossRef][Medline].
|
| 56.
|
Robey, W. G.,
B. Safai,
S. Oroszian,
L. Q. Arthur,
M. A. Gonda,
R. C. Gallo, and P. J. Fischinger.
1985.
Characterization of envelope and core gene products of HTLV-III with sera from AIDS patients.
Science
228:593-595[Abstract/Free Full Text].
|
| 57.
|
Rusche, J. R.,
D. Lynn,
M. Robert-Guroff,
A. Langlois,
H. Lyerly,
H. Carson,
K. Krohn,
A. Ranki,
R. Gallo,
D. Bolognesi, and S. Putney.
1987.
Humoral immune response to the entire human immunodeficiency virus envelope glycoprotein made in insect cells.
Proc. Natl. Acad. Sci. USA
84:6924-6928[Abstract/Free Full Text].
|
| 58.
|
Rusche, J. R.,
K. Javaherian,
C. McDanal,
J. Petro,
D. Lynn,
R. Grimaila,
A. Langlois,
R. C. Gallo,
L. Arthur,
P. J. Fischinger,
D. Bolognesi, and S. Putney.
1988.
Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120.
Proc. Natl. Acad. Sci. USA
85:3198-3202[Abstract/Free Full Text].
|
| 59.
|
Sawyer, L. S.,
M. T. Wrin,
L. Crawford-Miksza,
B. Potts,
Y. Wu,
P. A. Weber,
R. D. Alfonso, and C. V. Hanson.
1994.
Neutralization sensitivity of human immunodeficiency virus type 1 is determined in part by the cell in which the virus is propagated.
J. Virol.
68:1342-1349[Abstract/Free Full Text].
|
| 60.
|
Schotton, C.,
C. Arnold,
Q. Sattentau,
J. Sodroski, and J. McKeating.
1995.
Identification and characterization of monoclonal antibodies specific for polymorphic antigenic determinants within the V2 region of the human immunodeficiency virus type 1 envelope glycoprotein.
J. Virol.
69:222-230[Abstract].
|
| 61.
|
Schutten, M.,
A. McKnight,
R. C. Huisman,
M. Thali,
J. McKeating,
J. Sodroski,
J. Goudsmit, and A. D. Osterhaus.
1993.
Further characterization of an antigenic site of HIV-1 gp120 recognized by virus neutralizing human monoclonal antibodies.
AIDS
7:919-923[Medline].
|
| 62.
|
Schutten, M.,
A. C. Andeweg,
M. L. Bosch, and A. D. Osterhaus.
1995.
Enhancement of infectivity of a non-syncytium inducing HIV-1 by sCD4 and by human antibodies that neutralize syncytium inducing HIV-1.
Scand. J. Immunol.
41:18-22[CrossRef][Medline].
|
| 63.
|
Schutten, M.,
A. C. Andeweg,
G. Rimmelzwaan, and A. D. Osterhaus.
1997.
Modulation of primary HIV-1 envelope glycoprotein mediated entry by human antibodies.
J. Gen. Virol.
78:999-1006[Abstract].
|
| 64.
|
Sodroski, J.
1999.
HIV-1 entry inhibitors in the side pocket.
Cell
99:243-246[CrossRef][Medline].
|
| 65.
|
Steimer, K. S.,
C. J. Scandella,
P. V. Stiles, and N. L. Haigwood.
1991.
Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to Gp120.
Science
254:105-108[Abstract/Free Full Text].
|
| 66.
|
Sullivan, N.,
Y. Sun,
J. Li,
W. Hofmann, and J. Sodroski.
1995.
Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates.
J. Virol.
69:4413-4422[Abstract].
|
| 67.
|
Sullivan, N.,
Y. Sun,
J. Binley,
J. Lee,
C. F. Barbas III,
P. W. Parren,
D. R. Burton, and J. Sodroski.
1998.
Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies.
J. Virol.
72:6332-6338[Abstract/Free Full Text].
|
| 68.
|
Sullivan, N.,
Y. Sun,
Q. Sattentau,
M. Thali,
D. Wu,
G. Denisova,
J. Gershoni,
J. Robinson,
J. Moore, and J. Sodroski.
1998.
CD4-induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization.
J. Virol.
72:4694-4703[Abstract/Free Full Text].
|
| 69.
|
Tan, K.,
J.-H. Lee,
J.-H. Wang,
S. Shen, and M. Lu.
1997.
Atomic structure of a thermostable subdomain of HIV-1 gp41.
Proc. Natl. Acad. Sci. USA
94:12303-12308[Abstract/Free Full Text].
|
| 70.
|
Thali, M.,
U. Olshevsky,
C. Furman,
D. Gabuzda,
M. Posner, and J. Sodroski.
1991.
Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody.
J. Virol.
65:6188-6193[Abstract/Free Full Text].
|
| 71.
|
Thali, M.,
C. Furman,
D. D. Ho,
J. Robinson,
S. Tilley,
A. Pinter, and J. Sodroski.
1992.
Discontinuous, conserved neutralization epitopes overlapping the CD4-binding region of human immunodeficiency virus type 1 gp120 envelope glycoprotein.
J. Virol.
66:5635-5641[Abstract/Free Full Text].
|
| 72.
|
Thali, M.,
J. P. Moore,
C. Furman,
M. Charles,
D. D. Ho,
J. Robinson, and J. Sodroski.
1993.
Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.
J. Virol.
67:3978-3988[Abstract/Free Full Text].
|
| 73.
|
Tilley, S. A.,
W. J. Honnen,
M. Racho,
M. Hilgartner, and A. Pinter.
1991.
A human monoclonal antibody against the CD4-binding site of HIV-1 gp120 exhibits potent, broadly neutralizing activity.
Res. Virol.
142:247-259[CrossRef][Medline].
|
| 74.
|
Trkola, A.,
T. Dragic,
J. Arthos,
J. M. Binley,
W. C. Olson,
G. P. Allaway,
C. Cheng-Mayer,
J. Robinson,
P. J. Maddon, and J. P. Moore.
1996.
CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5.
Nature
384:184-187[CrossRef][Medline].
|
| 75.
|
VanCott, T. C.,
J. R. Mascola,
R. W. Kaminski,
V. Kalyaraman,
P. L. Hallberg,
P. R. Burnett,
J. T. Ulrich,
D. J. Rechtman, and D. L. Birx.
1997.
Antibodies with specificity to native gp120 and neutralization activity against primary human immunodeficiency virus type 1 isolates elicited by immunization with oligomeric gp160.
J. Virol.
71:4319-4330[Abstract].
|
| 76.
|
VanCott, T. C.,
J. R. Mascola,
L. D. Loomis-Price,
F. Sinangil,
N. Zitomersky,
J. McNeil,
M. L. Robb,
D. L. Birx, and S. Barnett.
1999.
Cross-subtype neutralizing antibodies induced in baboons by a subtype E gp120 immunogen based on an R5 primary human immunodeficiency virus type 1 envelope.
J. Virol.
73:4640-4650[Abstract/Free Full Text].
|
| 77.
|
Veronese, F. D.,
A. L. DeVico,
T. D. Copeland,
S. Oroszlan,
R. S. Gallo, and M. G. Sarngadharan.
1985.
Characterization of gp41 as the transmembrane protein coded by the HTLV-III/LAV envelope gene.
Science
229:1402-1405[Abstract/Free Full Text].
|
| 78.
|
Weissenhorn, W.,
A. Dessen,
S. C. Harrison,
J. J. Skehel, and D. C. Wiley.
1997.
Atomic structure of the ectodomain from HIV-1 gp41.
Nature
387:426-430[CrossRef][Medline].
|
| 79.
|
Wrin, T., and J. H. Nunberg.
1994.
HIV-1 MN recombinant gp120 vaccine serum, which fails to neutralize primary isolates of HIV-1, does not antagonize neutralization by antibodies from infected individuals.
AIDS
8:1622-1623[CrossRef][Medline].
|
| 80.
|
Wrin, T.,
T. P. Loh,
J. C. Vennari,
H. Schuitemaker, and J. H. Nunberg.
1995.
Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera.
J. Virol.
69:39-48[Abstract].
|
| 81.
|
Wu, L.,
N. P. Gerard,
R. Wyatt,
H. Choe,
C. Parolin,
N. Ruffing,
A. Borsetti,
A. A. Cardoso,
E. Desjardins,
W. Newman,
C. Gerard, and J. Sodroski.
1996.
CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5.
Nature
384:179-183[CrossRef][Medline].
|
| 82.
|
Wyatt, R., and J. Sodroski.
1998.
The human immunodeficiency virus (HIV-1) envelope glycoproteins: fusogens, antigens and immunogens.
Science
280:1884-1888[Abstract/Free Full Text].
|
| 83.
|
Wyatt, R.,
P. D. Kwong,
E. Desjardins,
R. W. Sweet,
J. Robinson,
W. A. Hendrickson, and J. G. Sodroski.
1998.
The antigenic structure of the HIV gp120 envelope glycoprotein.
Nature
393:705-711[CrossRef][Medline].
|
| 84.
|
Yang, X.,
L. Florin,
M. Farzan,
P. Kolchinsky,
P. Kwong,
J. Sodroski, and R. Wyatt.
1999.
Modifications that stabilize human immunodeficiency virus envelope glycoproteins trimers in solution.
J. Virol.
74:4746-4754[Abstract/Free Full Text].
|
| 85.
|
Yang, X.,
M. Farzan,
R. Wyatt, and J. Sodroski.
2000.
Characterization of stable, soluble trimers containing the complete ectodomains of the human immunodeficiency virus type 1 envelope glycoproteins.
J. Virol.
74:5716-5725[Abstract/Free Full Text].
|
| 86.
|
Zhang, Y.,
R. Fredriksson,
J. McKeating, and E. M. Fenyo.
1997.
Passage of HIV-1 molecular clones into different cells lines confers differential sensitivity to neutralization.
Virology
238:254-264[CrossRef][Medline].
|