Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells and Reagents
2.2. Design and Production of Immunoadhesins
2.3. ELISA
2.4. Indirect Immunofluorescence and Flow Cytometry
2.5. Cytotoxicity Assay
2.6. Neutralization Assays
2.7. Ab-Dependent Phagocytosis
3. Results
3.1. Production and Characterization of Immunoadhesins
3.2. Binding of Immunoadhesins to Antigen
3.3. Immunoconjugate Cytotoxicity
3.4. HIV Neutralization
3.5. Ab-Dependent Phagocytosis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Klasse, P.J.; Ozorowski, G.; Sanders, R.W.; Moore, J.P. Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immuno-gens? Cell Host Microbe 2020, 27, 507–518. [Google Scholar] [CrossRef]
- Haynes, B.F.; Burton, D.R.; Mascola, J.R. Multiple roles for HIV broadly neutralizing antibodies. Sci. Transl. Med. 2019, 11, eaaz2686. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sok, D.; Burton, D.R. Recent progress in broadly neutralizing antibodies to HIV. Nat. Immunol. 2018, 19, 1179–1188. [Google Scholar] [CrossRef] [PubMed]
- Kwong, P.D.; Mascola, J.R. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity 2018, 48, 855–871. [Google Scholar] [CrossRef] [Green Version]
- Ward, A.B.; A Wilson, I. The HIV-1 envelope glycoprotein structure: Nailing down a moving target. Immunol. Rev. 2017, 275, 21–32. [Google Scholar] [CrossRef] [PubMed]
- Julg, B.; Liu, P.-T.; Wagh, K.; Fischer, W.M.; Abbink, P.; Mercado, N.B.; Whitney, J.B.; Nkolola, J.P.; Mcmahan, K.; Tartaglia, L.J.; et al. Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail. Sci. Transl. Med. 2017, 9, eaao4235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pegu, A.; Borate, B.; Huang, Y.; Pauthner, M.G.; Hessell, A.J.; Julg, B.; Doria-Rose, N.A.; Schmidt, S.D.; Carpp, L.N.; Cully, M.D.; et al. A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge. Cell Host Microbe 2019, 26, 336–346.e3. [Google Scholar] [CrossRef]
- Grobben, M.; Stuart, R.A.; van Gils, M.J. The potential of engineered antibodies for HIV-1 therapy and cure. Curr. Opin. Virol. 2019, 38, 70–80. [Google Scholar] [CrossRef] [PubMed]
- Caskey, M.; Klein, F.; Nussenzweig, M.C. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat. Med. 2019, 25, 547–553. [Google Scholar] [CrossRef]
- Wu, X.; Guo, J.; Niu, M.; An, M.; Liu, L.; Wang, H.; Jin, X.; Zhang, Q.; Lam, K.S.; Wu, T.; et al. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J. Clin. Investig. 2018, 128, 2239–2251. [Google Scholar] [CrossRef] [Green Version]
- Mendoza, P.; Gruell, H.; Nogueira, L.; Pai, J.A.; Butler, A.L.; Millard, K.; Lehmann, C.; Suárez, I.; Oliveira, T.Y.; Lorenzi, J.C.C.; et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature 2018, 561, 479–484. [Google Scholar] [CrossRef]
- Mouquet, H. Hunting Down the HIV-1 Reservoir: A Starring Role for Antibodies? Immunity 2017, 46, 527–529. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gardner, M.R.; Farzan, M. Engineering antibody-like inhibitors to prevent and treat HIV-1 infection. Curr. Opin. HIV AIDS 2017, 12, 294–301. [Google Scholar] [CrossRef] [PubMed]
- Barouch, D.H.; Deeks, S.G. Immunologic strategies for HIV-1 remission and eradication. Science 2014, 345, 169–174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barouch, D.H.; Whitney, J.B.; Moldt, B.; Klein, F.; Oliveira, T.Y.; Liu, J.; Stephenson, K.; Chang, H.-W.; Shekhar, K.; Gupta, S.; et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 2013, 503, 224–228. [Google Scholar] [CrossRef] [Green Version]
- Tuyishime, M.; Garrido, C.; Jha, S.; Moeser, M.; Mielke, D.; LaBranche, C.; Montefiori, D.; Haynes, B.F.; Joseph, S.; Margolis, D.M.; et al. Improved killing of HIV-infected cells using three neutralizing and non-neutralizing antibodies. J. Clin. Investig. 2020, 130, 5157–5170. [Google Scholar] [CrossRef] [PubMed]
- Caskey, M.; Schoofs, T.; Gruell, H.; Settler, A.; Karagounis, T.; Kreider, E.F.; Murrell, B.; Pfeifer, N.; Nogueira, L.; Oliveira, T.Y.; et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat. Med. 2017, 23, 185–191. [Google Scholar] [CrossRef]
- Scheid, J.F.; Horwitz, J.A.; Bar-On, Y.; Kreider, E.; Lu, C.-L.; Lorenzi, J.C.C.; Feldmann, A.; Braunschweig, M.; Nogueira, L.; Oliveira, T.; et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature 2016, 535, 556–560. [Google Scholar] [CrossRef] [Green Version]
- Bar, K.J.; Sneller, M.C.; Harrison, L.J.; Justement, J.S.; Overton, E.T.; Petrone, M.E.; Salantes, D.B.; Seamon, C.A.; Scheinfeld, B.; Kwan, R.W.; et al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N. Engl. J. Med. 2016, 375, 2037–2050. [Google Scholar] [CrossRef]
- Lu, C.-L.; Murakowski, D.K.; Bournazos, S.; Schoofs, T.; Sarkar, D.; Halper-Stromberg, A.; Horwitz, J.A.; Nogueira, L.; Golijanin, J.; Gazumyan, A.; et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 2016, 352, 1001–1004. [Google Scholar] [CrossRef] [Green Version]
- Dey, B.; Del Castillo, C.S.; Berger, E.A. Neutralization of Human Immunodeficiency Virus Type 1 by sCD4-17b, a Single-Chain Chimeric Protein, Based on Sequential Interaction of gp120 with CD4 and Coreceptor. J. Virol. 2003, 77, 2859–2865. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Xiao, X.; Wang, Y.; Zhu, Z.; Dimitrov, D.S. Bifunctional fusion proteins of the human engineered antibody domain m36 with human soluble CD4 are potent inhibitors of diverse HIV-1 isolates. Antivir. Res. 2010, 88, 107–115. [Google Scholar] [CrossRef] [Green Version]
- West, A.P.; Galimidi, R.P.; Foglesong, C.P.; Gnanapragasam, P.N.P.; Klein, J.S.; Bjorkman, P.J. Evaluation of CD4-CD4i Antibody Architectures Yields Potent, Broadly Cross-Reactive Anti-Human Immunodeficiency Virus Reagents. J. Virol. 2010, 84, 261–269. [Google Scholar] [CrossRef] [Green Version]
- Craig, R.B.; Summa, C.M.; Corti, M.; Pincus, S.H. Anti-HIV Double Variable Domain Immunoglobulins Binding Both gp41 and gp120 for Targeted Delivery of Immunoconjugates. PLoS ONE 2012, 7, e46778. [Google Scholar] [CrossRef] [Green Version]
- Mouquet, H.; Warncke, M.; Scheid, J.F.; Seaman, M.S.; Nussenzweig, M.C. Enhanced HIV-1 neutralization by antibody heteroligation. Proc. Natl. Acad. Sci. USA 2012, 109, 875–880. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Davis-Gardner, M.E.; Alfant, B.; Weber, J.A.; Gardner, M.R.; Farzan, M. A Bispecific Antibody That Simultaneously Recognizes the V2- and V3-Glycan Epitopes of the HIV-1 Envelope Glycoprotein Is Broader and More Potent than Its Parental Antibodies. mBio 2020, 11, e03080-19. [Google Scholar] [CrossRef] [Green Version]
- Wagh, K.; Seaman, M.S.; Zingg, M.; Fitzsimons, T.; Barouch, D.H.; Burton, D.R.; Connors, M.; Ho, D.D.; Mascola, J.R.; Nussenzweig, M.C.; et al. Potential of conventional and bispecific broadly neutralizing an-tibodies for prevention of HIV-1 subtype A, C & D infections. PLoS Pathog. 2018, 14, e1006860. [Google Scholar]
- Xu, L.; Pegu, A.; Rao, E.; Doria-Rose, N.; Beninga, J.; McKee, K.; Lord, D.M.; Wei, R.R.; Deng, G.; Louder, M.; et al. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science 2017, 358, 85–90. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Montefiori, D.C. Bispecific Antibodies against HIV. Cell 2016, 165, 1563–1564. [Google Scholar] [CrossRef] [Green Version]
- Huang, Y.; Yu, J.; Lanzi, A.; Yao, X.; Andrews, C.D.; Tsai, L.; Gajjar, M.R.; Sun, M.; Seaman, M.S.; Padte, N.N.; et al. Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity. Cell 2016, 165, 1621–1631. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bournazos, S.; Gazumyan, A.; Seaman, M.S.; Nussenzweig, M.C.; Ravetch, J.V. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell 2016, 165, 1609–1620. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Asokan, M.; Rudicell, R.S.; Louder, M.; McKee, K.; O’Dell, S.; Stewart-Jones, G.; Wang, K.; Xu, L.; Chen, X.; Choe, M.; et al. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. J. Virol. 2015, 89, 12501–12512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, M.-Y.; Yuan, T.; Li, J.; Rosa Borges, A.; Watkins, J.D.; Guenaga, J.; Yang, Z.; Wang, Y.; Wilson, R.; Li, Y.; et al. Identification and Characterization of a Broadly Cross-Reactive HIV-1 Human Monoclonal Antibody That Binds to Both gp120 and gp41. PLoS ONE 2012, 7, e44241. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, J.; Kang, B.H.; Pancera, M.; Lee, J.H.; Tong, T.; Feng, Y.; Imamichi, H.; Georgiev, I.S.; Chuang, G.-Y.; Druz, A.; et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41–gp120 interface. Nature 2014, 515, 138–142. [Google Scholar] [CrossRef] [PubMed]
- Blattner, C.; Lee, J.H.; Sliepen, K.; Derking, R.; Falkowska, E.; de la Peña, A.T.; Cupo, A.; Julien, J.-P.; van Gils, M.; Lee, P.S.; et al. Structural Delineation of a Quaternary, Cleav-age-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity 2014. [Google Scholar] [CrossRef] [Green Version]
- Scharf, L.; Wang, H.; Gao, H.; Chen, S.; McDowall, A.W.; Bjorkman, P.J. Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env. Cell 2015, 162, 1379–1390. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lewis, G.K. Role of Fc-mediated antibody function in protective immunity against HIV-1. Immunology 2013, 142, 46–57. [Google Scholar] [CrossRef]
- Bournazos, S.; Klein, F.; Pietzsch, J.; Seaman, M.S.; Nussenzweig, M.C.; Ravetch, J.V. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell 2014, 158, 1243–1253. [Google Scholar] [CrossRef] [Green Version]
- McMahan, K.; Yu, J.; Mercado, N.B.; Loos, C.; Tostanoski, L.H.; Chandrashekar, A.; Liu, J.; Peter, L.; Atyeo, C.; Zhu, A.; et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 2021, 590, 630–634. [Google Scholar] [CrossRef]
- Loos, C.; Lauffenburger, D.A.; Alter, G. Dissecting the antibody-OME: Past, present, and future. Curr. Opin. Immunol. 2020, 65, 89–96. [Google Scholar] [CrossRef]
- Wang, P.; Gajjar, M.R.; Yu, J.; Padte, N.N.; Gettie, A.; Blanchard, J.L.; Russell-Lodrigue, K.; Liao, L.E.; Perelson, A.S.; Huang, Y.; et al. Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti–HIV-1 IgG1 antibodies in vivo. Proc. Natl. Acad. Sci. USA 2020, 117, 18002–18009. [Google Scholar] [CrossRef] [PubMed]
- Asokan, M.; Dias, J.; Liu, C.; Maximova, A.; Ernste, K.; Pegu, A.; McKee, K.; Shi, W.; Chen, X.; Almasri, C.; et al. Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody. Proc. Natl. Acad. Sci. USA 2020, 117, 18754–18763. [Google Scholar] [CrossRef] [PubMed]
- Horwitz, J.A.; Bar-On, Y.; Lu, C.-L.; Fera, D.; Lockhart, A.; Lorenzi, J.C.; Nogueira, L.; Golijanin, J.; Scheid, J.F.; Seaman, M.S.; et al. Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo. Cell 2017, 170, 637–648.e10. [Google Scholar] [CrossRef] [Green Version]
- Veillette, M.; Désormeaux, A.; Medjahed, H.; Gharsallah, N.-E.; Coutu, M.; Baalwa, J.; Guan, Y.; Lewis, G.; Ferrari, G.; Hahn, B.H.; et al. Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J. Virol. 2014, 88, 2633–2644. [Google Scholar] [CrossRef] [Green Version]
- Ferrari, G.; Pollara, J.; Kozink, D.M.; Harms, T.; Drinker, M.S.; Freel, S.A.; Moody, M.A.; Alam, S.M.; Tomaras, G.D.; Ochsenbauer, C.; et al. An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 Serum. J. Virol. 2011, 85, 7029–7036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pincus, S.H.; Song, K.; Maresh, G.A.; Hamer, D.H.; Dimitrov, D.S.; Chen, W.; Zhang, M.-Y.; Ghetie, V.F.; Chan-Hui, P.-Y.; Robinson, J.E.; et al. Identification of Human Anti-HIV gp160 Monoclonal Antibodies That Make Effective Immunotoxins. J. Virol. 2017, 91, e01955-16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pincus, S.H.; Song, K.; Maresh, G.A.; Frank, A.; Worthylake, D.; Chung, H.-K.; Polacino, P.; Hamer, D.H.; Coyne, C.P.; Rosenblum, M.G.; et al. Design and In Vivo Characterization of Immunoconjugates Targeting HIV gp160. J. Virol. 2017, 91, e01360-16. [Google Scholar] [CrossRef] [Green Version]
- Pincus, S.H.; McClure, J. Soluble CD4 enhances the efficacy of immunotoxins directed against gp41 of the human immunodefi-ciency virus. Proc. Natl. Acad. Sci. USA 1993, 90, 332–336. [Google Scholar] [CrossRef] [Green Version]
- Pincus, S.H.; Fang, H.; Wilkinson, R.A.; Marcotte, T.K.; Robinson, J.E.; Olson, W.C. In vivo efficacy of anti-gp41, but not anti-gp120, immunotoxins in a mouse model of HIV infection. J. Immunol. 2003, 170, 2236–2241. [Google Scholar] [CrossRef] [Green Version]
- Adachi, A.; Gendelman, H.E.; Koenig, S.; Folks, T.; Willey, R.; Rabson, A.; Martin, M.A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 1986, 59, 284–291. [Google Scholar] [CrossRef] [Green Version]
- Pincus, S.H.; Wehrly, K. AZT Demonstrates Anti-HIV-l Activity in Persistently Infected Cell Lines: Implications for Combination Chemotherapy and Immunotherapy. J. Infect. Dis. 1990, 162, 1233–1238. [Google Scholar] [CrossRef]
- Chen, J.; Kovacs, J.M.; Peng, H.; Rits-Volloch, S.; Lu, J.; Park, D.; Zablowsky, E.; Seaman, M.S.; Chen, B. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein. Science 2015, 349, 191–195. [Google Scholar] [CrossRef] [Green Version]
- Garlick, R.L.; Kirschner, R.J.; Eckenrode, F.M.; Tarpley, W.G.; Tomich, C.-S.C. Escherichia coli Expression, Purification, and Biological Activity of a Truncated Soluble CD4. AIDS Res. Hum. Retrovir. 1990, 6, 465–479. [Google Scholar] [CrossRef] [PubMed]
- Gauduin, M.-C.; Allaway, G.P.; Olson, W.C.; Weir, R.; Maddon, P.J.; Koup, R.A. CD4-IgG2 protects Hu-PBL-SCID mice against challenge by primary HIV-1 isolates. J. Virol. 1998, 72, 3475–3478. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shearer, W.T.; Israel, R.J.; Starr, S.; Fletcher, C.V.; Wara, D.; Rathore, M.; Church, J.; DeVille, J.; Fenton, T.; Graham, B.; et al. Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: Phase 1/2 study. J. Infect. Dis. 2000, 182, 1774–1779. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allaway, G.P.; Davis-Bruno, K.L.; Beaudry, G.A.; Garcia, E.B.; Wong, E.L.; Ryder, A.M.; Hasel, K.W.; Gauduin, M.-C.; Koup, R.A.; McDougal, J.S.; et al. Expression and Characterization of CD4-IgG2, a Novel Heterotetramer That Neutralizes Primary HIV Type 1 Isolates. AIDS Res. Hum. Retrovir. 1995, 11, 533–539. [Google Scholar] [CrossRef]
- Bonsignori, M.; Montefiori, D.C.; Wu, X.; Chen, X.; Hwang, K.-K.; Tsao, C.-Y.; Kozink, D.M.; Parks, R.J.; Tomaras, G.D.; Crump, J.A.; et al. Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor, Implications for Vaccine Design. J. Virol. 2012, 86, 4688–4692. [Google Scholar] [CrossRef] [Green Version]
- Pincus, S.H.; Johnson, C.; Maresh, G.; Song, K. Improving Anti-Ricin Antibodies: Chimerization and Selection of Ricin-Resistant Hybridoma Cell Lines. In Ricin Toxin, 1st ed.; Cherwonogrodzky, J.W., Ed.; Bentham Science Publisher: Sharjah, United Arab Emirates, 2014; Volume 1, pp. 130–144. [Google Scholar]
- Robinson, J.E.; Hastie, K.M.; Cross, R.W.; Yenni, R.E.; Elliott, D.H.; Rouelle, J.A.; Kannadka, C.B.; Smira, A.A.; Garry, C.E.; Bradley, B.T.; et al. Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits. Nat. Commun. 2016, 7, 11544. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Feng, Y.; Prabakaran, P.; Ying, T.; Wang, Y.; Sun, J.; Macedo, C.D.S.; Zhu, Z.; He, Y.; Polonis, V.R.; et al. Exceptionally Potent and Broadly Cross-Reactive, Bispecific Multivalent HIV-1 Inhibitors Based on Single Human CD4 and Antibody Domains. J. Virol. 2013, 88, 1125–1139. [Google Scholar] [CrossRef] [Green Version]
- Hinton, P.R.; Johlfs, M.G.; Xiong, J.M.; Hanestad, K.; Ong, K.C.; Bullock, C.; Keller, S.; Tang, M.T.; Tso, J.Y.; Vásquez, M.; et al. Engineered Human IgG Antibodies with Longer Serum Half-lives in Primates. J. Biol. Chem. 2004, 279, 6213–6216. [Google Scholar] [CrossRef] [Green Version]
- Sellhorn, G.; Caldwell, Z.; Mineart, C.; Stamatatos, L. Improving the expression of recombinant soluble HIV Envelope glycoproteins using pseudo-stable transient transfection. Vaccine 2009, 28, 430–436. [Google Scholar] [CrossRef]
- Till, M.; May, R.D.; Uhr, J.W.; Thorpe, P.E.; Vitetta, E.S. An assay that predicts the ability of monoclonal antibodies to form potent ricin A chain-containing immunotoxins. Cancer Res. 1988, 48, 1119–1123. [Google Scholar] [PubMed]
- Sarzotti-Kelsoe, M.; Bailer, R.T.; Turk, E.; Lin, C.-L.; Bilska, M.; Greene, K.M.; Gao, H.; Todd, C.A.; Ozaki, D.A.; Seaman, M.S.; et al. Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1. J. Immunol. Methods 2014, 409, 131–146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Decamp, A.; Hraber, P.; Bailer, R.T.; Seaman, M.S.; Ochsenbauer, C.; Kappes, J.; Gottardo, R.; Edlefsen, P.; Self, S.; Tang, H.; et al. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol. 2014, 88, 2489–2507. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoon, H.; Macke, J.; West, A.P.; Foley, B.; Bjorkman, P.J.; Korber, B.; Yusim, K. CATNAP: A tool to compile, analyze and tally neutralizing antibody panels. Nucleic Acids Res. 2015, 43, W213–W219. [Google Scholar] [CrossRef] [Green Version]
- Ackerman, M.E.; Moldt, B.; Wyatt, R.T.; Dugast, A.-S.; McAndrew, E.; Tsoukas, S.; Jost, S.; Berger, C.T.; Sciaranghella, G.; Liu, Q.; et al. A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples. J. Immunol. Methods 2011, 366, 8–19. [Google Scholar] [CrossRef] [Green Version]
- Pincus, S.H.; Wehrly, K.; Cole, R.; Fang, H.; Lewis, G.K.; McClure, J.; Conley, A.J.; Wahren, B.; Posner, M.R.; Notkins, A.L.; et al. In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on the HIV-1 envelope glycoprotein gp160. AIDS Res. Hum. Retrovir. 1996, 12, 1041–1051. [Google Scholar] [CrossRef]
- Jacobson, J.M.; Lowy, I.; Fletcher, C.V.; O’Neill, T.J.; Tran, D.N.; Ketas, T.J.; Trkola, A.; Klotman, M.E.; Maddon, P.J.; Olson, W.C.; et al. Single-dose safety, pharmacology, and antiviral activity of HIV type 1 entry inhibitor PRO 542 in HIV-infected adults. J. Infect. Dis. 2000, 182, 326–329. [Google Scholar] [CrossRef] [Green Version]
- Forthal, D.N.; Gilbert, P.B.; Landucci, G.; Phan, T. Recombinant gp120 Vaccine-Induced Antibodies Inhibit Clinical Strains of HIV-1 in the Presence of Fc Receptor-Bearing Effector Cells and Correlate Inversely with HIV Infection Rate. J. Immunol. 2007, 178, 6596–6603. [Google Scholar] [CrossRef] [PubMed]
- Montefiori, D.C.; Interrante, M.V.F.; Bell, B.N.; Rubio, A.A.; Joyce, J.G.; Shiver, J.W.; LaBranche, C.C.; Kim, P.S. The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat. Proc. Natl. Acad. Sci. USA 2021, 118. [Google Scholar] [CrossRef] [PubMed]
- May, R.D.; Wheeler, H.T.; Finkelman, F.D.; Uhr, J.W.; Vitetta, E.S. Intracellular routing rather than cross-linking or rate of internali-zation determines the potency of immunotoxins directed against different epitopes of sigD on murine B cells. Cell Immunol. 1991, 135, 490–500. [Google Scholar] [CrossRef]
- May, R.D.; Finkelman, F.D.; Wheeler, H.T.; Uhr, J.W.; Vitetta, E.S. Evaluation of ricin A chain-containing immunotoxins directed against different epitopes on the delta-chain of cell surface-associated IgD on murine B cells. J. Immunol. 1990, 144, 3637–3642. [Google Scholar] [PubMed]
Name | H Chain | L Chain | CD4 | Linker |
---|---|---|---|---|
CD4(D1)-2H2-7B2 | CD4(D1)-2H2-7B2 | 7B2k | CD4(D1.22) | (GGGGS)2-A(EAAK)4A-(GGGGS)2 |
CD4(D1)-H4-7B2 | CD4(D1)-H4-7B2 | 7B2k | CD4(D1.22) | A(EAAK)4A |
CD4(D2)-2H2-7B2 | CD4(D2)-2H2-7B2 | 7B2k | CD4183 | (GGGGS)2-A(EAAK)4A-(GGGGS)2 |
CD4(D2)-H4-7B2 | CD4(D2)-H4-7B2 | 7B2k | CD4183 | A(EAAK)4A |
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Pincus, S.H.; Craig, R.B.; Weachter, L.; LaBranche, C.C.; Nabi, R.; Watt, C.; Raymond, M.; Peters, T.; Song, K.; Maresh, G.A.; et al. Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines 2021, 9, 774. https://doi.org/10.3390/vaccines9070774
Pincus SH, Craig RB, Weachter L, LaBranche CC, Nabi R, Watt C, Raymond M, Peters T, Song K, Maresh GA, et al. Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines. 2021; 9(7):774. https://doi.org/10.3390/vaccines9070774
Chicago/Turabian StylePincus, Seth H., Ryan B. Craig, Lauren Weachter, Celia C. LaBranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, and et al. 2021. "Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity" Vaccines 9, no. 7: 774. https://doi.org/10.3390/vaccines9070774
APA StylePincus, S. H., Craig, R. B., Weachter, L., LaBranche, C. C., Nabi, R., Watt, C., Raymond, M., Peters, T., Song, K., Maresh, G. A., Montefiori, D. C., & Kozlowski, P. A. (2021). Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines, 9(7), 774. https://doi.org/10.3390/vaccines9070774