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2. Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens

Author

Crooks, Emma T., primary, Almanza, Francisco, additional, D’Addabbo, Alessio, additional, Duggan, Erika, additional, Zhang, Jinsong, additional, Wagh, Kshitij, additional, Mou, Huihui, additional, Allen, Joel D., additional, Thomas, Alyssa, additional, Osawa, Keiko, additional, Korber, Bette T., additional, Tsybovsky, Yaroslav, additional, Cale, Evan, additional, Nolan, John, additional, Crispin, Max, additional, Verkoczy, Laurent K., additional, and Binley, James M., additional

Published
2021
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3. Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens

Author

Crooks, Emma T, primary, Almanza, Francisco, additional, D’addabbo, Alessio, additional, Duggan, Erika, additional, Zhang, Jinsong, additional, Wagh, Kshitij, additional, Mou, Huihui, additional, Allen, Joel D, additional, Thomas, Alyssa, additional, Osawa, Keiko, additional, Korber, Bette T, additional, Tsybovsky, Yaroslav, additional, Cale, Evan, additional, Nolan, John, additional, Crispin, Max, additional, Verkoczy, Laurent K, additional, and Binley, James M, additional

Published
2021
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4. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env

Author

Do Kwon, Young, primary, Pancera, Marie, additional, Acharya, Priyamvada, additional, Georgiev, Ivelin S, additional, Crooks, Emma T, additional, Gorman, Jason, additional, Joyce, M Gordon, additional, Guttman, Miklos, additional, Ma, Xiaochu, additional, Narpala, Sandeep, additional, Soto, Cinque, additional, Terry, Daniel S, additional, Yang, Yongping, additional, Zhou, Tongqing, additional, Ahlsen, Goran, additional, Bailer, Robert T, additional, Chambers, Michael, additional, Chuang, Gwo-Yu, additional, Doria-Rose, Nicole A, additional, Druz, Aliaksandr, additional, Hallen, Mark A, additional, Harned, Adam, additional, Kirys, Tatsiana, additional, Louder, Mark K, additional, O'Dell, Sijy, additional, Ofek, Gilad, additional, Osawa, Keiko, additional, Prabhakaran, Madhu, additional, Sastry, Mallika, additional, Stewart-Jones, Guillaume B E, additional, Stuckey, Jonathan, additional, Thomas, Paul V, additional, Tittley, Tishina, additional, Williams, Constance, additional, Zhang, Baoshan, additional, Zhao, Hong, additional, Zhou, Zhou, additional, Donald, Bruce R, additional, Lee, Lawrence K, additional, Zolla-Pazner, Susan, additional, Baxa, Ulrich, additional, Schön, Arne, additional, Freire, Ernesto, additional, Shapiro, Lawrence, additional, Lee, Kelly K, additional, Arthos, James, additional, Munro, James B, additional, Blanchard, Scott C, additional, Mothes, Walther, additional, Binley, James M, additional, McDermott, Adrian B, additional, Mascola, John R, additional, and Kwong, Peter D, additional

Published
2015
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6. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals

Author

Tomaras, Georgia D., primary, Binley, James M., additional, Gray, Elin S., additional, Crooks, Emma T., additional, Osawa, Keiko, additional, Moore, Penny L., additional, Tumba, Nancy, additional, Tong, Tommy, additional, Shen, Xiaoying, additional, Yates, Nicole L., additional, Decker, Julie, additional, Wibmer, Constantinos Kurt, additional, Gao, Feng, additional, Alam, S. Munir, additional, Easterbrook, Philippa, additional, Abdool Karim, Salim, additional, Kamanga, Gift, additional, Crump, John A., additional, Cohen, Myron, additional, Shaw, George M., additional, Mascola, John R., additional, Haynes, Barton F., additional, Montefiori, David C., additional, and Morris, Lynn, additional

Published
2011
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8. Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1

Author

Kang, Yun (Kenneth), primary, Andjelic, Sofija, additional, Binley, James M., additional, Crooks, Emma T., additional, Franti, Michael, additional, Iyer, Sai Prasad N., additional, Donovan, Gerald P., additional, Dey, Antu K., additional, Zhu, Ping, additional, Roux, Kenneth H., additional, Durso, Robert J., additional, Parsons, Thomas F., additional, Maddon, Paul J., additional, Moore, John P., additional, and Olson, William C., additional

Published
2009
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9. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C

Author

Binley, James M., primary, Lybarger, Elizabeth A., additional, Crooks, Emma T., additional, Seaman, Michael S., additional, Gray, Elin, additional, Davis, Katie L., additional, Decker, Julie M., additional, Wycuff, Diane, additional, Harris, Linda, additional, Hawkins, Natalie, additional, Wood, Blake, additional, Nathe, Cory, additional, Richman, Douglas, additional, Tomaras, Georgia D., additional, Bibollet-Ruche, Frederic, additional, Robinson, James E., additional, Morris, Lynn, additional, Shaw, George M., additional, Montefiori, David C., additional, and Mascola, John R., additional

Published
2008
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12. A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120

Author

Crooks, Emma T., primary, Moore, Penny L., additional, Franti, Michael, additional, Cayanan, Charmagne S., additional, Zhu, Ping, additional, Jiang, Pengfei, additional, de Vries, Robbert P., additional, Wiley, Cheryl, additional, Zharkikh, Irina, additional, Schülke, Norbert, additional, Roux, Kenneth H., additional, Montefiori, David C., additional, Burton, Dennis R., additional, and Binley, James M., additional

Published
2007
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13. An Affinity-Enhanced Neutralizing Antibody against the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 Recognizes an Epitope between Those of 2F5 and 4E10

Author

Nelson, Josh D., primary, Brunel, Florence M., additional, Jensen, Richard, additional, Crooks, Emma T., additional, Cardoso, Rosa M. F., additional, Wang, Meng, additional, Hessell, Ann, additional, Wilson, Ian A., additional, Binley, James M., additional, Dawson, Philip E., additional, Burton, Dennis R., additional, and Zwick, Michael B., additional

Published
2007
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14. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIV SF162P4 and Heterologous HIV-1 Infection

Author

Derby, Nina R., primary, Kraft, Zane, additional, Kan, Elaine, additional, Crooks, Emma T., additional, Barnett, Susan W., additional, Srivastava, Indresh K., additional, Binley, James M., additional, and Stamatatos, Leonidas, additional

Published
2007
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15. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIV SF162P4 and Heterologous HIV-1 Infection

Author

Derby, Nina R., primary, Kraft, Zane, additional, Kan, Elaine, additional, Crooks, Emma T., additional, Barnett, Susan W., additional, Srivastava, Indresh K., additional, Binley, James M., additional, and Stamatatos, Leonidas, additional

Published
2006
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17. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1

Author

Moore, Penny L., primary, Crooks, Emma T., additional, Porter, Lauren, additional, Zhu, Ping, additional, Cayanan, Charmagne S., additional, Grise, Henry, additional, Corcoran, Paul, additional, Zwick, Michael B., additional, Franti, Michael, additional, Morris, Lynn, additional, Roux, Kenneth H., additional, Burton, Dennis R., additional, and Binley, James M., additional

Published
2006
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18. Characterizing anti-HIV monoclonal antibodies and immune sera by defining the mechanism of neutralization.

Author

Crooks, Emma T., Moore, Penny L., Richman, Douglas, Robinson, James, Crooks, Jeffrey A., Franti, Michael, Schülke, Norbert, and Binley, James M.

Subjects
*VIRAL vaccines, *AIDS vaccines, *MONOCLONAL antibodies, *IMMUNOGLOBULINS, *BLOOD plasma
Abstract

Understanding the nature of neutralization may provide information for crafting improvements in HIV vaccines. Using JR-FL as a prototype primary pseudovirus, we first investigated anti-HIV monoclonal antibodies (mAbs) in several neutralization formats designed to elucidate the timing of neutralization. MAb b12 was most effective before receptor binding, 2G12 neutralized effectively even after CD4 binding, and X5 and a V3 loop mAb (LE311) were inactive in a standard format but were induced by sCD4. Consistent with this latter finding, native PAGE indicated that X5 and V3 mAb binding to Envelope trimers was dependent on sCD4 binding. In contrast, 2F5 and 4E10 were active even post-CD4/CCR5 engagement. We next analyzed the neutralization mechanism of a panel of HIV+ donor plasmas of various potencies. All mediated high levels of post-CD4 neutralization that was not associated with activity in the standard format. None, however, neutralized effectively in the post-CD4/CCR5 format, suggesting that 2F5/4E10-like Abs were absent or at low concentrations. Finally, we analyzed a non-neutralizing plasma spiked with mAbs b12, 2G12 or 2F5, which resulted in increases in neutralization titers consistent with the activities of the mAbs. We conclude that these methods, together with other mapping approaches, may provide a better understanding of neutralization that could be useful in vaccine research. [ABSTRACT FROM AUTHOR]

Published
2005

19. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection.

Author

Derby, Nina R., Kraft, Zane, Kan, Elaine, Crooks, Emma T., Barnett, Susan W., Srivastava, Indresh K., Binley, James M., and Stamatatos, Leonidas

Subjects
*RHESUS monkeys, *MACAQUES, *HIV, *HTLV, *VIRUSES
Abstract

The antibody responses elicited in rhesus macaques immunized with soluble human immunodeficiency virus (HIV) Env gp140 proteins derived from the R5-tropic HIV-1 SF162 virus were analyzed and compared to the broadly reactive neutralizing antibody responses elicited during chronic infection of a macaque with a simian/human immunodeficiency virus (SHIV) expressing the HIV-1 SF162 Env, SHIVSF162P4, and humans infected with heterologous HIV-1 isolates. Four gp140 immunogens were evaluated: SF162gp140, ΔV2gp140 (lacking the crown of the V2 loop), ΔV3gp140 (lacking the crown of the V3 loop), and ΔV2 ΔV3gp140 (lacking both the V2 and V3 loop crowns). SF162gp140 and ΔV2gp140 have been previously evaluated by our group in a pilot study, but here, a more comprehensive analysis of their immunogenic properties was performed. All four gp140 immunogens elicited stronger anti-gp120 than anti-gp41 antibodies and potent homologous neutralizing antibodies (NAbs) that primarily targeted the first hypervariable region (V1 loop) of gp120, although SF162gp140 also elicited anti-V3 NAbs. Heterologous NAbs were elicited by SF162gp140 and ΔV2gp140 but were weak in potency and narrow in specificity. No heterologous NAbs were elicited by ΔV3gp140 or ΔV2 ΔV3gp140. In contrast, the SHIVSF162P4-infected macaque and HIV-infected humans generated similar titers of anti-gp120 and anti-gp41 antibodies and NAbs of significant breadth against primary HIV-1 isolates, which did not target the V1 loop. The difference in V1 loop immunogenicity between soluble gp140 and virion-associated gp160 Env proteins derived from SF162 may be the basis for the observed difference in the breadth of neutralization in sera from the immunized and infected animals studied here. [ABSTRACT FROM AUTHOR]

Published
2006
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20. Impact of Glycan Depletion, Glycan Debranching and Increased Glycan Charge on HIV-1 Neutralization Sensitivity and Immunogenicity.

Author

D'Addabbo A, Tong T, Crooks ET, Osawa K, Xu J, Thomas A, Allen JD, Crispin M, and Binley JM

Abstract

Broadly neutralizing antibodies (bNAbs) isolated from HIV-1 infected donors are vaccine paradigms. These bNAbs recognize envelope glycoprotein trimers that carry 75-90 oligomannose and complex-type glycans. Although bNAbs and their precursors must navigate past glycans, they usually also make some glycan contacts. Glycan-modified vaccines may therefore be useful to initiate and guide bNAb development. Here, we describe two ways to modify Env glycans for possible vaccine use: 1) using a cocktail of glycosidases (termed "NGAF3" (Neuraminidase, β-Galactosidase, N-Acetylglucosaminidase, endoglycosidase F3 (endo F3)) to deplete complex glycans to try to minimize bNAb-glycan clashes and 2) co-expressing β-1,4-galactosyltransferase 1 (B4G) and β-galactoside α-2,6 sialyltransferase 1 (ST6) during Env biosynthesis, creating bNAb-preferred glycan structures. Mass spectrometry revealed that NGAF3 removed glycan heads at 3/7 sites occupied by complex glycans. B4G overexpression resulted in hybrid glycan development whenever complex glycans were closely spaced. The glycan at position 611 in of Env's gp41 transmembrane subunit was uniquely isolated from the effects of both endo F3 and B4G. B4G and ST6 co-expression increased hybrid and sialylated glycan abundance, reducing glycan complexity. In rabbit vaccinations, B4G + ST6 virus-like particles (VLPs) induced less frequent, weaker titer NAbs, implying that ST6-mediated increased Env charge dampens vaccine antibodies. In some cases, vaccine sera preferentially neutralized B4G + ST6-modified pseudovirus. HIV-1+ donor plasma NAbs were generally more effective against B4G + ST6 modified pseudovirus, suggesting a preference for less complex and/or α-2,6 sialylated Env trimers. Collectively, our data suggest that B4G and ST6 Env modifications are best suited for intermediate or late vaccine shots., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2024
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21. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.

Author

Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Gorman J, Joyce MG, Guttman M, Ma X, Narpala S, Soto C, Terry DS, Yang Y, Zhou T, Ahlsen G, Bailer RT, Chambers M, Chuang GY, Doria-Rose NA, Druz A, Hallen MA, Harned A, Kirys T, Louder MK, O'Dell S, Ofek G, Osawa K, Prabhakaran M, Sastry M, Stewart-Jones GB, Stuckey J, Thomas PV, Tittley T, Williams C, Zhang B, Zhao H, Zhou Z, Donald BR, Lee LK, Zolla-Pazner S, Baxa U, Schön A, Freire E, Shapiro L, Lee KK, Arthos J, Munro JB, Blanchard SC, Mothes W, Binley JM, McDermott AB, Mascola JR, and Kwong PD

Subjects
CD4 Antigens immunology, Crystallography, X-Ray, Epitopes immunology, HEK293 Cells, HIV Infections virology, HIV-1 chemistry, HIV-1 immunology, Humans, Models, Molecular, Protein Conformation, Protein Multimerization, Virus Internalization, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV Infections immunology, HIV-1 physiology, env Gene Products, Human Immunodeficiency Virus chemistry, env Gene Products, Human Immunodeficiency Virus immunology
Abstract

As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones. We coupled these compatibility considerations with binding antigenicity to engineer conformationally fixed Envs, including a 201C 433C (DS) variant specifically recognized by broadly neutralizing antibodies. DS-Env retained nanomolar affinity for the CD4 receptor, with which it formed an asymmetric intermediate: a closed trimer bound by a single CD4 without the typical antigenic hallmarks of CD4 induction. Antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like-particle and soluble formats providing a new generation of vaccine antigens.

Published
2015
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