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Anti-HIV-1 Antibodies: An Update

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Abstract

Even after more than 30 years since its discovery, there is no cure for HIV-1 infection. Combination antiretroviral therapy (cART) is currently the only HIV-1 infection management option in clinics. Despite its success in suppressing viral replication and converting HIV-1 from a lethal infection to a chronic and manageable disease, cART treatment is life long and long-term use can result in major drawbacks such as high cost, multiple side effects, and an increase in the development of multidrug-resistant escape mutants. Recently, antibody-based anti-HIV-1 treatment has emerged as a potential alternative therapeutic modality for HIV-1 treatment and cure strategies. These antibody-based anti-HIV-1 treatments comprising either receptor-targeting antibodies or broad neutralizing antibodies (bNAbs) are currently being developed and evaluated in clinical trials. These antibodies have demonstrated potent antiviral effects against multiple strains of HIV-1, and shown promise for prevention, maintenance, and prolonged remission of HIV-1 infection. This review gives an update on the current status of these antibody-based treatments for HIV-1, discusses their mechanism of action and the challenges in developing them, providing insight for their development as novel clinical therapies against HIV-1 infection.

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References

  1. Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet. 1998;352(9142):1725–30.

    Article  CAS  PubMed  Google Scholar 

  2. Trovato M, D’Apice L, Prisco A, et al. HIV vaccination: a roadmap among advancements and concerns. Int J Mol Sci. 2018;19(4):E1241. https://doi.org/10.3390/ijms19041241.

    Article  CAS  PubMed  Google Scholar 

  3. Awi NJ, Teow SY. Antibody-mediated therapy against HIV/AIDS: where are we standing now? J Pathog. 2018;2018:8724549.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Oguntibeju OO. Quality of life of people living with HIV and AIDS and antiretroviral therapy. HIV AIDS (Auckl). 2012;4:117–24.

    Google Scholar 

  5. Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med. 1997;337(11):734–9.

    Article  CAS  PubMed  Google Scholar 

  6. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337(11):725–33.

    Article  CAS  PubMed  Google Scholar 

  7. Sengupta S, Siliciano RF. Targeting the latent reservoir for HIV-1. Immunity. 2018;48(5):872–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chun TW, Davey RT Jr, Engel D, et al. Re-emergence of HIV after stopping therapy. Nature. 1999;401(6756):874–5.

    Article  CAS  PubMed  Google Scholar 

  9. Kaufmann GR, Khanna N, Weber R, et al. Long-term virological response to multiple sequential regimens of highly active antiretroviral therapy for HIV infection. Antivir Ther. 2004;9(2):263–74.

    CAS  PubMed  Google Scholar 

  10. Larder BA, Darby G, Richman DD. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989;243(4899):1731–4.

    Article  CAS  PubMed  Google Scholar 

  11. Smith LK, Kuhn TB, Chen J, et al. HIV associated neurodegenerative disorders: a new perspective on the role of lipid rafts in Gp120-mediated neurotoxicity. Curr HIV Res. 2018;16(4):258–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen YF, Dugas TR. Endothelial mitochondrial senescence accelerates cardiovascular disease in antiretroviral-receiving HIV patients. Toxicol Lett. 2019;317:13–23.

    Article  CAS  PubMed  Google Scholar 

  13. Yuan NY, Kaul M. Beneficial and adverse effects of cART affect neurocognitive function in HIV-1 infection: balancing viral suppression against neuronal stress and injury. J Neuroimmune Pharmacol. 2019. https://doi.org/10.1007/s11481-019-09868-9.

  14. Demir OM, Candilio L, Fuster D, et al. Cardiovascular disease burden among human immunodeficiency virus-infected individuals. Int J Cardiol. 2018;265:195–203.

    Article  PubMed  Google Scholar 

  15. Margolis DM, Garcia JV, Hazuda DJ, et al. Latency reversal and viral clearance to cure HIV-1. Science. 2016;353(6297):aaf6517.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. UNAIDS Data 2019. 2019. https://www.unaids.org/sites/default/files/media_asset/2019-UNAIDS-data_en.pdf. Accessed 30 Jan 2020.

  17. Caskey M, Klein F, Nussenzweig MC. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat Med. 2019;25(4):547–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gama L, Koup RA. New-generation high-potency and designer antibodies: role in HIV-1 treatment. Annu Rev Med. 2018;69:409–19.

    Article  CAS  PubMed  Google Scholar 

  19. Parsons MS, Chung AW, Kent SJ. Importance of Fc-mediated functions of anti-HIV-1 broadly neutralizing antibodies. Retrovirology. 2018;15(1):58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012;12(4):278–87.

    Article  CAS  PubMed  Google Scholar 

  22. Salazar G, Zhang N, Fu TM, et al. Antibody therapies for the prevention and treatment of viral infections. NPJ Vaccines. 2017;2:19.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Henrich TJ, Kuritzkes DR. HIV-1 entry inhibitors: recent development and clinical use. Curr Opin Virol. 2013;3(1):51–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Thompson MA. The return of PRO 140, a CCR5-directed mAb. Curr Opin HIV AIDS. 2018;13(4):346–53.

    Article  CAS  PubMed  Google Scholar 

  25. Beccari MV, Mogle BT, Sidman EF, et al. Ibalizumab, a novel monoclonal antibody for the management of multidrug-resistant HIV-1 infection. Antimicrob Agents Chemother. 2019;63(6):e00110-19. https://doi.org/10.1128/AAC.00110-19.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang CY, Wong WW, Tsai HC, et al. Effect of anti-CD4 antibody UB-421 on HIV-1 rebound after treatment interruption. N Engl J Med. 2019;380(16):1535–45.

    Article  CAS  PubMed  Google Scholar 

  27. Trogarzo (ibalizumab-uiyk): pipeline status. 2019. http://www.taimedbiologics.com/pipeline/33. Accessed 30 Jan 2020.

  28. Emu B, Fessel J, Schrader S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1. N Engl J Med. 2018;379(7):645–54.

    Article  CAS  PubMed  Google Scholar 

  29. Song R, Franco D, Kao CY, et al. Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. J Virol. 2010;84(14):6935–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kuritzkes DR, Jacobson J, Powderly WG, et al. Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1. J Infect Dis. 2004;189(2):286–91.

    Article  CAS  PubMed  Google Scholar 

  31. Jacobson JM, Kuritzkes DR, Godofsky E, et al. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009;53(2):450–7.

    Article  CAS  PubMed  Google Scholar 

  32. Norris D, Morales J, Godofsky E, Garcia F, Hardwicke R, Lewis S. TNX-355, in combination with optimized background regimen (OBR), achieves statistically significant viral load reduction and CD4 cell count increase when compared with OBR alone in phase 2 study at 48 weeks in AIDS Toronto; 2006. Oral abstract session: Abstract no. THLB0218.

  33. NCT00784147: dose-response study of ibalizumab (monoclonal antibody) plus optimized background regimen in patients with HIV-1. 1/30/2020]. https://ClinicalTrials.gov/show/NCT00784147. Accessed 30 Jan 2020.

  34. NCT02475629: ibalizumab plus optimized background regimen in patient with multi-drug resistant HIV. https://ClinicalTrials.gov/show/NCT02475629. Accessed 30 Jan 2020.

  35. Wang CY, Sawyer LS, Murthy KK, et al. Postexposure immunoprophylaxis of primary isolates by an antibody to HIV receptor complex. Proc Natl Acad Sci USA. 1999;96(18):10367–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. NCT01668043: study to evaluate safety and efficacy of UB-421 antibody in HIV-1 infected adults. https://ClinicalTrials.gov/show/NCT01668043. Accessed 30 Jan 2020.

  37. Olson WC, Rabut GE, Nagashima KA, et al. Differential inhibition of human immunodeficiency virus type 1 fusion, gp120 binding, and CC-chemokine activity by monoclonal antibodies to CCR5. J Virol. 1999;73(5):4145–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Trkola A, Ketas TJ, Nagashima KA, et al. Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J Virol. 2001;75(2):579–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jacobson JM, Thompson MA, Lalezari JP, et al. Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody. J Infect Dis. 2010;201(10):1481–7.

    Article  CAS  PubMed  Google Scholar 

  40. NCT02355184: an extension of protocol PRO 140_CD01 TS study. https://ClinicalTrials.gov/show/NCT02355184. Accessed 30 Jan 2020.

  41. Cavacini LA, Samore MH, Gambertoglio J, et al. Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120. AIDS Res Hum Retrovir. 1998;14(7):545–50.

    Article  CAS  PubMed  Google Scholar 

  42. Dezube BJ, Doweiko JP, Proper JA, et al. Monoclonal antibody hNM01 in HIV-infected patients: a phase I study. J Clin Virol. 2004;31(Suppl 1):S45–7.

    Article  CAS  PubMed  Google Scholar 

  43. Hinkula J, Bratt G, Gilljam G, et al. Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies. J Acquir Immune Defic Syndr. 1994;7(9):940–51.

    CAS  PubMed  Google Scholar 

  44. Matsushita S, Yoshimura K, Ramirez KP, et al. Passive transfer of neutralizing mAb KD-247 reduces plasma viral load in patients chronically infected with HIV-1. AIDS. 2015;29(4):453–62.

    Article  CAS  PubMed  Google Scholar 

  45. Gunthard HF, Gowland PL, Schupbach J, et al. A phase I/IIA clinical study with a chimeric mouse-human monoclonal antibody to the V3 loop of human immunodeficiency virus type 1 gp120. J Infect Dis. 1994;170(6):1384–93.

    Article  CAS  PubMed  Google Scholar 

  46. Trkola A, Kuster H, Rusert P, et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med. 2005;11(6):615–22.

    Article  CAS  PubMed  Google Scholar 

  47. Mehandru S, Vcelar B, Wrin T, et al. Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J Virol. 2007;81(20):11016–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Scheid JF, Mouquet H, Feldhahn N, et al. A method for identification of HIV gp140 binding memory B cells in human blood. J Immunol Methods. 2009;343(2):65–7.

    Article  CAS  PubMed  Google Scholar 

  49. Walker LM, Phogat SK, Chan-Hui PY, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326(5950):285–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Simek MD, Rida W, Priddy FH, et al. Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol. 2009;83(14):7337–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wu X, Yang ZY, Li Y, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010;329(5993):856–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Burton DR, Hangartner L. Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu Rev Immunol. 2016;34:635–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Pancera M, Changela A, Kwong PD. How HIV-1 entry mechanism and broadly neutralizing antibodies guide structure-based vaccine design. Curr Opin HIV AIDS. 2017;12(3):229–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ledgerwood JE, Coates EE, Yamshchikov G, et al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015;182(3):289–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lynch RM, Boritz E, Coates EE, et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med. 2015;7(319):319ra206.

    Article  PubMed  CAS  Google Scholar 

  56. Crowell TA, Colby DJ, Pinyakorn S, et al. Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet HIV. 2019;6(5):e297–306.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Caskey M, Klein F, Lorenzi JC, et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015;522(7557):487–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Caskey M, Schoofs T, Gruell H, et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat Med. 2017;23(2):185–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gaudinski MR, Houser KV, Doria-Rose NA, et al. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Lancet HIV. 2019;6(10):e667–79.

    Article  PubMed  Google Scholar 

  60. Bar KJ, Sneller MC, Harrison LJ, et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N Engl J Med. 2016;375(21):2037–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535(7613):556–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Riddler SA, Zheng L, Durand CM, et al. Randomized clinical trial to assess the impact of the broadly neutralizing HIV-1 monoclonal antibody VRC01 on HIV-1 persistence in individuals on effective ART. Open Forum Infect Dis. 2018;5(10):ofy242.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Cohen YZ, Lorenzi JCC, Krassnig L, et al. Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117. J Exp Med. 2018;215(9):2311–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Borducchi EN, Liu J, Nkolola JP, et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature. 2018;563(7731):360–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang Y, Karuna S, Carpp LN, et al. Modeling cumulative overall prevention efficacy for the VRC01 phase 2b efficacy trials. Hum Vaccin Immunother. 2018;14(9):2116–27.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Cohen YZ, Butler AL, Millard K, et al. Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: a randomized, phase 1 study. PLoS One. 2019;14(8):e0219142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bar-On Y, Gruell H, Schoofs T, et al. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat Med. 2018;24(11):1701–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mendoza P, Gruell H, Nogueira L, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018;561(7724):479–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. NCT03721510: a phase 1/2a study of PGT121, VRC07-523LS and PGDM1400 monoclonal antibodies in HIV-uninfected and HIV-infected adults. https://clinicaltrials.gov/ct2/show/study/NCT03721510. Accessed 30 Jan 2020.

  70. Labrijn AF, Janmaat ML, Reichert JM, et al. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18(8):585–608.

    Article  CAS  PubMed  Google Scholar 

  71. Fabozzi G, Pegu A, Koup RA, et al. Bispecific antibodies: potential immunotherapies for HIV treatment. Methods. 2019;154:118–24.

    Article  CAS  PubMed  Google Scholar 

  72. Padte NN, Yu J, Huang Y, et al. Engineering multi-specific antibodies against HIV-1. Retrovirology. 2018;15(1):60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Sloan DD, Lam CY, Irrinki A, et al. Targeting HIV reservoir in infected CD4 T cells by dual-affinity re-targeting molecules (DARTs) that bind HIV envelope and recruit cytotoxic T cells. PLoS Pathog. 2015;11(11):e1005233.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Sung JA, Pickeral J, Liu L, et al. Dual-affinity re-targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells. J Clin Investig. 2015;125(11):4077–90.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Huang Y, Yu J, Lanzi A, et al. Engineered bispecific antibodies with exquisite HIV-1-neutralizing activity. Cell. 2016;165(7):1621–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Xu L, Pegu A, Rao E, et al. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science. 2017;358(6359):85–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Schott AK, Pries R, Wollenberg B. Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer. Int J Mol Med. 2010;26(1):67–75.

    CAS  PubMed  Google Scholar 

  78. Steinhardt JJ, Guenaga J, Turner HL, et al. Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity. Nat Commun. 2018;9(1):877.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Khan SN, Sok D, Tran K et al. Targeting the HIV-1 spike and coreceptor with bi- and trispecific antibodies for single-component broad inhibition of entry. J Virol. 2018;92(18):e00384-18. https://doi.org/10.1128/JVI.00384-18.

  80. NCT03705169: Pharmacokinetics of SAR441236. https://ClinicalTrials.gov/show/NCT03705169. Accessed 30 Jan 2020.

  81. Asokan M, Rudicell RS, Louder M, et al. Bispecific antibodies targeting different epitopes on the HIV-1 envelope exhibit broad and potent neutralization. J Virol. 2015;89(24):12501–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bournazos S, Gazumyan A, Seaman MS, et al. Bispecific Anti-HIV-1 antibodies with enhanced breadth and potency. Cell. 2016;165(7):1609–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pegu A, Asokan M, Wu L, et al. Activation and lysis of human CD4 cells latently infected with HIV-1. Nat Commun. 2015;6:8447.

    Article  CAS  PubMed  Google Scholar 

  84. Brozy J, Schlaepfer E, Mueller CKS, et al. Antiviral activity of HIV gp120-targeting bispecific T cell engager antibody constructs. J Virol. 2018;92(14):e00491-18. https://doi.org/10.1128/JVI.00491-18.

    Article  PubMed  PubMed Central  Google Scholar 

  85. NCT03875209: 10E8.4/iMab bispecific antibody in HIV-uninfected and HIV-infected adults. https://ClinicalTrials.gov/show/NCT03875209. Accessed 30 Jan 2020.

  86. NCT03570918: MGD014 in HIV-infected individuals on suppressive antiretroviral therapy. https://ClinicalTrials.gov/show/NCT03570918. Accessed 30 Jan 2020.

  87. Buie LW, Pecoraro JJ, Horvat TZ, et al. Blinatumomab: a first-in-class bispecific T-cell engager for precursor B-cell acute lymphoblastic leukemia. Ann Pharmacother. 2015;49(9):1057–67.

    Article  CAS  PubMed  Google Scholar 

  88. Zalevsky J, Chamberlain AK, Horton HM, et al. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol. 2010;28(2):157–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ko SY, Pegu A, Rudicell RS, et al. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature. 2014;514(7524):642–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Gautam R, Nishimura Y, Gaughan N, et al. A single injection of crystallizable fragment domain-modified antibodies elicits durable protection from SHIV infection. Nat Med. 2018;24(5):610–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gaudinski MR, Coates EE, Houser KV, et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: a Phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018;15(1):e1002493.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Bournazos S, Klein F, Pietzsch J, et al. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell. 2014;158(6):1243–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Schoofs T, Klein F, Braunschweig M, et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016;352(6288):997–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Zhang Z, Guan Q, Yuan H. HIV-1 Broadly neutralizing antibodies: identification, development and vaccine evaluation. J AIDS Clin Res. 2016;7(12):1000636. https://doi.org/10.4172/2155-6113.1000636.

  95. Caskey M, Klein F, Nussenzweig MC. Broadly neutralizing antibodies for HIV-1 prevention or immunotherapy. N Engl J Med. 2016;375(21):2019–21.

    Article  CAS  PubMed  Google Scholar 

  96. Ponsel D, Neugebauer J, Ladetzki-Baehs K, et al. High affinity, developability and functional size: the holy grail of combinatorial antibody library generation. Molecules. 2011;16(5):3675–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Halper-Stromberg A, Lu CL, Klein F, et al. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell. 2014;158(5):989–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Gruell H, Klein F. Antibody-mediated prevention and treatment of HIV-1 infection. Retrovirology. 2018;15(1):73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lin A, Balazs AB. Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1. Retrovirology. 2018;15(1):66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Burton DR. Advancing an HIV vaccine; advancing vaccinology. Nat Rev Immunol. 2019;19(2):77–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. van den Bemt BJF, Gettings L, Domanska B, et al. A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience. Drug Deliv. 2019;26(1):384–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. NCT00642707: study of PRO 140 by subcutaneous administration in adult subjects with HIV-1 infection. https://ClinicalTrials.gov/show/NCT00642707. Accessed 30 Jan 2020.

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Acknowledgements

This research was supported by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health. We would also like to thank Brenda Hartman for assistance with the graphics.

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  1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Wanwisa Promsote, Megan E. DeMouth, Cassandra G. Almasri & Amarendra Pegu

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  1. Wanwisa Promsote
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  2. Megan E. DeMouth
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WP, MED, CGA, and AP wrote and edited the manuscript. All authors have approved the submission.

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Correspondence to Amarendra Pegu.

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AP is listed as an inventor on a patent titled “Trispecific and/or trivalent binding proteins for prevention or treatment of HIV infection” that describes the anti-HIV-1 trispecific antibodies. The other authors declare that no conflict of interest exists.

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Promsote, W., DeMouth, M.E., Almasri, C.G. et al. Anti-HIV-1 Antibodies: An Update. BioDrugs 34, 121–132 (2020). https://doi.org/10.1007/s40259-020-00413-2

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