Identification of variant HIV envelope proteins with enhanced affinities for precursors to anti-gp41 broadly neutralizing antibodies

English version

Autoři: Hong Zhu ^aff001; Elizabeth Mathew ^aff001; Sara M. Connelly ^aff001; Jeffrey Zuber ^aff001; Mark Sullivan ^aff002; Michael S. Piepenbrink ^aff003; James J. Kobie ^aff003; Mark E. Dumont ^aff001
Působiště autorů: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, United States of America ^aff001; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, United States of America ^aff002; Infectious Diseases Division, University of Rochester Medical Center, Rochester, NY United States of America ^aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0221550

Souhrn

HIV envelope protein (Env) is the sole target of broadly neutralizing antibodies (BNAbs) that are capable of neutralizing diverse strains of HIV. While BNAbs develop spontaneously in a subset of HIV-infected patients, efforts to design an envelope protein-based immunogen to elicit broadly neutralizing antibody responses have so far been unsuccessful. It is hypothesized that a primary barrier to eliciting BNAbs is the fact that HIV envelope proteins bind poorly to the germline-encoded unmutated common ancestor (UCA) precursors to BNAbs. To identify variant forms of Env with increased affinities for the UCA forms of BNAbs 4E10 and 10E8, which target the Membrane Proximal External Region (MPER) of Env, libraries of randomly mutated Env variants were expressed in a yeast surface display system and screened using fluorescence activated cell sorting for cells displaying variants with enhanced abilities to bind the UCA antibodies. Based on analyses of individual clones obtained from the screen and on next-generation sequencing of sorted libraries, distinct but partially overlapping sets of amino acid substitutions conferring enhanced UCA antibody binding were identified. These were particularly enriched in substitutions of arginine for highly conserved tryptophan residues. The UCA-binding variants also generally exhibited enhanced binding to the mature forms of anti-MPER antibodies. Mapping of the identified substitutions into available structures of Env suggest that they may act by destabilizing both the initial pre-fusion conformation and the six-helix bundle involved in fusion of the viral and cell membranes, as well as providing new or expanded epitopes with increased accessibility for the UCA antibodies.

Klíčová slova:

Biology and life sciences – Cell biology – Genetics – Biochemistry – Organisms – Eukaryota – Research and analysis methods – Proteins – Fungi – Yeast – Molecular biology – Molecular biology techniques – Medicine and health sciences – Mutation – Cloning – Microbiology – Medical microbiology – Microbial pathogens – Pathology and laboratory medicine – Pathogens – Physiology – Molecular biology assays and analysis techniques – Viral pathogens – Immunodeficiency viruses – HIV – Retroviruses – Lentivirus – Viruses – RNA viruses – Immunology – Immune physiology – Library screening – Immune system proteins – Antibodies – Cell physiology – Substitution mutation – Mutagenesis – Cell binding

Zdroje

1. Fauci AS. An HIV Vaccine Is Essential for Ending the HIV/AIDS Pandemic. JAMA. 2017;318(16):1535–6. doi: 10.1001/jama.2017.13505 29052689

2. Gao Y, McKay PF, Mann JFS. Advances in HIV-1 Vaccine Development. Viruses. 2018;10(4).

3. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209–20. doi: 10.1056/NEJMoa0908492 19843557

4. Kwong PD, Mascola JR. HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity. 2018;48(5):855–71. doi: 10.1016/j.immuni.2018.04.029 29768174

5. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012;491(7424):406–12. doi: 10.1038/nature11544 23151583

6. Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, et al. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual. Immunity. 2019;50(3):677–91 e13. doi: 10.1016/j.immuni.2019.02.008 30876875

7. Williams LD, Ofek G, Schatzle S, McDaniel JR, Lu X, Nicely NI, et al. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Science immunology. 2017;2(7).

8. Banerjee S, Shi H, Banasik M, Moon H, Lees W, Qin Y, et al. Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region. Virology. 2017;505:113–26. doi: 10.1016/j.virol.2017.02.015 28237764

9. Beltran-Pavez C, Ferreira CB, Merino-Mansilla A, Fabra-Garcia A, Casadella M, Noguera-Julian M, et al. Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant. PLoS One. 2018;13(12):e0208345. doi: 10.1371/journal.pone.0208345 30566493

10. Correia BE, Ban YE, Holmes MA, Xu H, Ellingson K, Kraft Z, et al. Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope. Structure. 2010;18(9):1116–26. doi: 10.1016/j.str.2010.06.010 20826338

11. Ma BJ, Alam SM, Go EP, Lu X, Desaire H, Tomaras GD, et al. Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies. PLoS Pathog. 2011;7(9):e1002200. doi: 10.1371/journal.ppat.1002200 21909262

12. Xiao X, Chen W, Feng Y, Zhu Z, Prabakaran P, Wang Y, et al. Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens. Biochem Biophys Res Commun. 2009;390(3):404–9. doi: 10.1016/j.bbrc.2009.09.029 19748484

13. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira TY, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science. 2011;333(6049):1633–7. doi: 10.1126/science.1207227 21764753

14. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477(7365):466–70. doi: 10.1038/nature10373 21849977

15. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326(5950):285–9. doi: 10.1126/science.1178746 19729618

16. Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, et al. Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors. J Virol. 2011.

17. Huber M, Le KM, Doores KJ, Fulton Z, Stanfield RL, Wilson IA, et al. Very few substitutions in a germ line antibody are required to initiate significant domain exchange. J Virol. 2010;84(20):10700–7. doi: 10.1128/JVI.01111-10 20702640

18. Yuan T, Li J, Zhang MY. A single mutation turns a non-binding germline-like predecessor of broadly neutralizing antibody into a binding antibody to HIV-1 envelope glycoproteins. MAbs. 2011;3(4).

19. Hoot S, McGuire AT, Cohen KW, Strong RK, Hangartner L, Klein F, et al. Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs. PLoS Pathog. 2013;9(1):e1003106. doi: 10.1371/journal.ppat.1003106 23300456

20. Klein F, Diskin R, Scheid JF, Gaebler C, Mouquet H, Georgiev IS, et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell. 2013;153(1):126–38. doi: 10.1016/j.cell.2013.03.018 23540694

21. Briney B, Sok D, Jardine JG, Kulp DW, Skog P, Menis S, et al. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell. 2016;166(6):1459–70 e11. doi: 10.1016/j.cell.2016.08.005 27610570

22. Jardine J, Julien JP, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science. 2013;340(6133):711–6. doi: 10.1126/science.1234150 23539181

23. Jardine JG, Kulp DW, Havenar-Daughton C, Sarkar A, Briney B, Sok D, et al. HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science. 2016;351(6280):1458–63. doi: 10.1126/science.aad9195 27013733

24. Jardine JG, Ota T, Sok D, Pauthner M, Kulp DW, Kalyuzhniy O, et al. HIV-1 VACCINES. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science. 2015;349(6244):156–61. doi: 10.1126/science.aac5894 26089355

25. Xu K, Acharya P, Kong R, Cheng C, Chuang GY, Liu K, et al. Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat Med. 2018;24(6):857–67. doi: 10.1038/s41591-018-0042-6 29867235

26. McGuire AT, Hoot S, Dreyer AM, Lippy A, Stuart A, Cohen KW, et al. Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies. J Exp Med. 2013;210(4):655–63. doi: 10.1084/jem.20122824 23530120

27. Bruun TH, Muhlbauer K, Benen T, Kliche A, Wagner R. A mammalian cell based FACS-panning platform for the selection of HIV-1 envelopes for vaccine development. PLoS One. 2014;9(10):e109196. doi: 10.1371/journal.pone.0109196 25279768

28. Steichen JM, Kulp DW, Tokatlian T, Escolano A, Dosenovic P, Stanfield RL, et al. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies. Immunity. 2016;45(3):483–96. doi: 10.1016/j.immuni.2016.08.016 27617678

29. Escolano A, Steichen JM, Dosenovic P, Kulp DW, Golijanin J, Sok D, et al. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice. Cell. 2016;166(6):1445–58 e12. doi: 10.1016/j.cell.2016.07.030 27610569

30. Zwick MB, Labrijn AF, Wang M, Spenlehauer C, Saphire EO, Binley JM, et al. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol. 2001;75(22):10892–905. doi: 10.1128/JVI.75.22.10892-10905.2001 11602729

31. Grimm SK, Battles MB, Ackerman ME. Directed evolution of a yeast-displayed HIV-1 SOSIP gp140 spike protein toward improved expression and affinity for conformational antibodies. PLoS One. 2015;10(2):e0117227. doi: 10.1371/journal.pone.0117227 25688555

32. Sanders RW, Vesanen M, Schuelke N, Master A, Schiffner L, Kalyanaraman R, et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2002;76(17):8875–89. doi: 10.1128/JVI.76.17.8875-8889.2002 12163607

33. Mathew E, Zhu H, Connelly SM, Sullivan MA, Brewer MG, Piepenbrink MS, et al. Display of the HIV envelope protein at the yeast cell surface for immunogen development. PLoS One. 2018;13(10):e0205756. doi: 10.1371/journal.pone.0205756 30335821

34. Angelini A, Chen TF, de Picciotto S, Yang NJ, Tzeng A, Santos MS, et al. Protein Engineering and Selection Using Yeast Surface Display. Methods Mol Biol. 2015;1319:3–36. doi: 10.1007/978-1-4939-2748-7_1 26060067

35. McGuire AT, Glenn JA, Lippy A, Stamatatos L. Diverse recombinant HIV-1 Envs fail to activate B cells expressing the germline B cell receptors of the broadly neutralizing anti-HIV-1 antibodies PG9 and 447-52D. J Virol. 2014;88(5):2645–57. doi: 10.1128/JVI.03228-13 24352455

36. Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med. 1998;338(3):161–5. doi: 10.1056/NEJM199801153380304 9428817

37. Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013;9(9):e1003618. doi: 10.1371/journal.ppat.1003618 24068931

38. Cardoso RM, Brunel FM, Ferguson S, Zwick M, Burton DR, Dawson PE, et al. Structural basis of enhanced binding of extended and helically constrained peptide epitopes of the broadly neutralizing HIV-1 antibody 4E10. J Mol Biol. 2007;365(5):1533–44. doi: 10.1016/j.jmb.2006.10.088 17125793

39. Stiegler G, Kunert R, Purtscher M, Wolbank S, Voglauer R, Steindl F, et al. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 2001;17(18):1757–65. doi: 10.1089/08892220152741450 11788027

40. Purtscher M, Trkola A, Gruber G, Buchacher A, Predl R, Steindl F, et al. A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1994;10(12):1651–8. doi: 10.1089/aid.1994.10.1651 7888224

41. Ofek G, Tang M, Sambor A, Katinger H, Mascola JR, Wyatt R, et al. Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J Virol. 2004;78(19):10724–37. doi: 10.1128/JVI.78.19.10724-10737.2004 15367639

42. Tian Y, Ramesh CV, Ma X, Naqvi S, Patel T, Cenizal T, et al. Structure-affinity relationships in the gp41 ELDKWA epitope for the HIV-1 neutralizing monoclonal antibody 2F5: effects of side-chain and backbone modifications and conformational constraints. J Pept Res. 2002;59(6):264–76. 12010517

43. Zwick MB, Jensen R, Church S, Wang M, Stiegler G, Kunert R, et al. Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J Virol. 2005;79(2):1252–61. doi: 10.1128/JVI.79.2.1252-1261.2005 15613352

44. Rockwell NC, Krysan DJ, Komiyama T, Fuller RS. Precursor processing by kex2/furin proteases. Chem Rev. 2002;102(12):4525–48. 12475200

45. Rockwell NC, Wang GT, Krafft GA, Fuller RS. Internally consistent libraries of fluorogenic substrates demonstrate that Kex2 protease specificity is generated by multiple mechanisms. Biochemistry. 1997;36(7):1912–7. doi: 10.1021/bi961779l 9048578

46. Kumar S, Sarkar A, Pugach P, Sanders RW, Moore JP, Ward AB, et al. Capturing the inherent structural dynamics of the HIV-1 envelope glycoprotein fusion peptide. Nat Commun. 2019;10(1):763. doi: 10.1038/s41467-019-08738-5 30770829

47. Lee JH, Ozorowski G, Ward AB. Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science. 2016;351(6277):1043–8. doi: 10.1126/science.aad2450 26941313

48. Fu Q, Shaik MM, Cai Y, Ghantous F, Piai A, Peng H, et al. Structure of the membrane proximal external region of HIV-1 envelope glycoprotein. Proc Natl Acad Sci U S A. 2018;115(38):E8892–E9. doi: 10.1073/pnas.1807259115 30185554

49. Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997;89(2):263–73. doi: 10.1016/s0092-8674(00)80205-6 9108481

50. Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature. 1997;387(6631):426–30. doi: 10.1038/387426a0 9163431

51. Frey G, Chen J, Rits-Volloch S, Freeman MM, Zolla-Pazner S, Chen B. Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies. Nat Struct Mol Biol. 2010;17(12):1486–91. doi: 10.1038/nsmb.1950 21076402

52. Frey G, Peng H, Rits-Volloch S, Morelli M, Cheng Y, Chen B. A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies. Proc Natl Acad Sci U S A. 2008;105(10):3739–44. doi: 10.1073/pnas.0800255105 18322015

53. Sun ZY, Oh KJ, Kim M, Yu J, Brusic V, Song L, et al. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity. 2008;28(1):52–63. doi: 10.1016/j.immuni.2007.11.018 18191596

54. Irimia A, Sarkar A, Stanfield RL, Wilson IA. Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10. Immunity. 2016;44(1):21–31. doi: 10.1016/j.immuni.2015.12.001 26777395

55. Irimia A, Serra AM, Sarkar A, Jacak R, Kalyuzhniy O, Sok D, et al. Lipid interactions and angle of approach to the HIV-1 viral membrane of broadly neutralizing antibody 10E8: Insights for vaccine and therapeutic design. PLoS Pathog. 2017;13(2):e1006212. doi: 10.1371/journal.ppat.1006212 28225819

56. Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014;514(7523):455–61. doi: 10.1038/nature13808 25296255

57. Chan DC, Chutkowski CT, Kim PS. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc Natl Acad Sci U S A. 1998;95(26):15613–7. doi: 10.1073/pnas.95.26.15613 9861018

58. Wang S, York J, Shu W, Stoller MO, Nunberg JH, Lu M. Interhelical interactions in the gp41 core: implications for activation of HIV-1 membrane fusion. Biochemistry. 2002;41(23):7283–92. doi: 10.1021/bi025648y 12044159

59. York J, Nunberg JH. Role of hydrophobic residues in the central ectodomain of gp41 in maintaining the association between human immunodeficiency virus type 1 envelope glycoprotein subunits gp120 and gp41. J Virol. 2004;78(9):4921–6. doi: 10.1128/JVI.78.9.4921-4926.2004 15078976

60. Salzwedel K, West JT, Hunter E. A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. J Virol. 1999;73(3):2469–80. 9971832

61. Buzon V, Natrajan G, Schibli D, Campelo F, Kozlov MM, Weissenhorn W. Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions. PLoS Pathog. 2010;6(5):e1000880. doi: 10.1371/journal.ppat.1000880 20463810

62. Bellamy-McIntyre AK, Lay CS, Baar S, Maerz AL, Talbo GH, Drummer HE, et al. Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. J Biol Chem. 2007;282(32):23104–16. doi: 10.1074/jbc.M703485200 17526486

63. Banerjee S, Shi H, Habte HH, Qin Y, Cho MW. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure. Virology. 2016;490:17–26. doi: 10.1016/j.virol.2016.01.002 26803471

64. Rathinakumar R, Dutta M, Zhu P, Johnson WE, Roux KH. Binding of anti-membrane-proximal gp41 monoclonal antibodies to CD4-liganded and -unliganded human immunodeficiency virus type 1 and simian immunodeficiency virus virions. J Virol. 2012;86(3):1820–31. doi: 10.1128/JVI.05489-11 22090143

65. Mata-Fink J, Kriegsman B, Yu HX, Zhu H, Hanson MC, Irvine DJ, et al. Rapid conformational epitope mapping of anti-gp120 antibodies with a designed mutant panel displayed on yeast. J Mol Biol. 2013;425(2):444–56. doi: 10.1016/j.jmb.2012.11.010 23159556

66. Finney J, Kelsoe G. Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design. Retrovirology. 2018;15(1):53. doi: 10.1186/s12977-018-0435-0 30055635

67. Kelsoe G, Haynes BF. Host controls of HIV broadly neutralizing antibody development. Immunol Rev. 2017;275(1):79–88. doi: 10.1111/imr.12508 28133807

68. Verkoczy L, Chen Y, Zhang J, Bouton-Verville H, Newman A, Lockwood B, et al. Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses. J Immunol. 2013;191(5):2538–50. doi: 10.4049/jimmunol.1300971 23918977

69. Wansley EK, Chakraborty M, Hance KW, Bernstein MB, Boehm AL, Guo Z, et al. Vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicits therapeutic antitumor responses. Clin Cancer Res. 2008;14(13):4316–25. doi: 10.1158/1078-0432.CCR-08-0393 18594015

70. Chen Y, Zhang J, Hwang KK, Bouton-Verville H, Xia SM, Newman A, et al. Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 4E10. J Immunol. 2013;191(3):1260–75. doi: 10.4049/jimmunol.1300770 23825311

71. Doyle-Cooper C, Hudson KE, Cooper AB, Ota T, Skog P, Dawson PE, et al. Immune tolerance negatively regulates B cells in knock-in mice expressing broadly neutralizing HIV antibody 4E10. J Immunol. 2013;191(6):3186–91. doi: 10.4049/jimmunol.1301285 23940276

72. Finton KA, Larimore K, Larman HB, Friend D, Correnti C, Rupert PB, et al. Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation of the anti-HIV antibody 4E10. PLoS Pathog. 2013;9(9):e1003639. doi: 10.1371/journal.ppat.1003639 24086134

73. Ardiani A, Higgins JP, Hodge JW. Vaccines based on whole recombinant Saccharomyces cerevisiae cells. FEMS Yeast Res. 2010;10(8):1060–9. doi: 10.1111/j.1567-1364.2010.00665.x 20707820

74. Bal J, Luong NN, Park J, Song KD, Jang YS, Kim DH. Comparative immunogenicity of preparations of yeast-derived dengue oral vaccine candidate. Microb Cell Fact. 2018;17(1):24. doi: 10.1186/s12934-018-0876-0 29452594

75. King TH, Shanley CA, Guo Z, Bellgrau D, Rodell T, Furney S, et al. GI-19007, a Novel Saccharomyces cerevisiae-Based Therapeutic Vaccine against Tuberculosis. Clin Vaccine Immunol. 2017;24(12).

76. Kumar R, Kumar P. Yeast-based vaccines: New perspective in vaccine development and application. FEMS Yeast Res. 2019;19(2).

77. Sullivan MA, Brooks LR, Weidenborner P, Domm W, Mattiacio J, Xu Q, et al. Anti-idiotypic monobodies derived from a fibronectin scaffold. Biochemistry. 2013;52(10):1802–13. doi: 10.1021/bi3016668 23394681

78. Soto C, Ofek G, Joyce MG, Zhang B, McKee K, Longo NS, et al. Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8. PLoS One. 2016;11(6):e0157409. doi: 10.1371/journal.pone.0157409 27299673

79. Wang Z, Mathias A, Stavrou S, Neville DM Jr. A new yeast display vector permitting free scFv amino termini can augment ligand binding affinities. Protein Eng Des Sel. 2005;18(7):337–43. doi: 10.1093/protein/gzi036 15976011

80. Benatuil L, Perez JM, Belk J, Hsieh CM. An improved yeast transformation method for the generation of very large human antibody libraries. Protein Eng Des Sel. 2010;23(4):155–9. doi: 10.1093/protein/gzq002 20130105

81. Huang R, Fang P, Kay BK. Improvements to the Kunkel mutagenesis protocol for constructing primary and secondary phage-display libraries. Methods. 2012;58(1):10–7. doi: 10.1016/j.ymeth.2012.08.008 22959950

82. Celic A, Connelly SM, Martin NP, Dumont ME. Intensive mutational analysis of G protein-coupled receptors in yeast. Methods Mol Biol. 2004;237:105–20. doi: 10.1385/1-59259-430-1:105 14501043

83. Kunkel TA. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985;82(2):488–92. doi: 10.1073/pnas.82.2.488 3881765

84. Mathew E, Dumont ME. A Novel Screening Approach for Optimal and Functional Fusion of T4 Lysozyme in GPCRs. Methods Enzymol. 2015;557:27–43. doi: 10.1016/bs.mie.2014.12.031 25950958

85. Schulke N, Vesanen MS, Sanders RW, Zhu P, Lu M, Anselma DJ, et al. Oligomeric and conformational properties of a proteolytically mature, disulfide-stabilized human immunodeficiency virus type 1 gp140 envelope glycoprotein. J Virol. 2002;76(15):7760–76. doi: 10.1128/JVI.76.15.7760-7776.2002 12097589

86. Sievers F, Higgins DG. Clustal Omega, accurate alignment of very large numbers of sequences. Methods Mol Biol. 2014;1079:105–16. doi: 10.1007/978-1-62703-646-7_6 24170397

Identification of variant HIV envelope proteins with enhanced affinities for precursors to anti-gp41 broadly neutralizing antibodies

Souhrn

Klíčová slova:

Zdroje

PLOS One

Aktuální možnosti diagnostiky a léčby litiáz