Production and Immunogenicity of Soluble Plant-Produced HIV-1 Subtype C Envelope gp140 Immunogens

Frontiers in Plant Science

Volumn 10, Issue , 2019, Pages

  Margolin, Emmanuel ^a,b   Chapman, Rosamund ^a   Meyers, Ann E ^b   van Diepen, Michiel T ^a   Ximba, Phindile ^a,b   Hermanus, Tandile ^c,d   Crowther, Carol ^c,d   Weber, Brandon ^b   Morris, Lynn ^c,d   Williamson, Anna Lise ^a   Rybicki, Edward P ^a,b  

^a UNIVERSITY OF CAPE TOWN   (South Africa)

^b UNIVERSITY OF CAPE TOWN   (South Africa)

^c NATIONAL INSTITUTE FOR COMMUNICABLE DISEASES   (South Africa)

^d UNIVERSITY OF THE WITWATERSRAND   (South Africa)

Author keywords

glycoprotein; HIV; immunogenicity; modified vaccinia Ankara; plants

Indexed keywords

EID: 85075231964     PISSN: None     EISSN: 1664462X     Source Type: Journal    
DOI: 10.3389/fpls.2019.01378     Document Type: Article

References (88)

1. Alter G., Barouch D., (2018). Immune Correlate-Guided HIV Vaccine Design. Cell Host Microbe 24 (1), 25–33. doi: 10.1016/j.chom.2018.06.012
2. Bachmann M. F., Jennings G. T., (2010). Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat. Rev. Immunol. 10 (11), 787–796. doi: 10.1038/nri2868
3. Bachmann M. F., Rohrer U. H., Kundig T. M., Burki K., Hengartner H., Zinkernagel R. M., (1993). The influence of antigen organization on B cell responsiveness. Science 262 (5138), 1448–1451. doi: 10.1126/science.8248784
4. Barouch D. H., Alter G., Broge T., Linde C., Ackerman M. E., Brown E. P.. (2015). Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science 349 (6245), 320–324. doi: 10.1126/science.aab3886
5. Bhiman J. N., Anthony C., Doria-Rose N. A., Karimanzira O., Schramm C. A., Khoza T.. (2015). Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies. Nat. Med. 21 (11), 1332–1336. doi: 10.1038/nm.3963
6. Blish C. A., Dogan O. C., Derby N. R., Nguyen M. A., Chohan B., Richardson B. A.. (2008). Human immunodeficiency virus type 1 superinfection occurs despite relatively robust neutralizing antibody responses. J. Virol. 82 (24), 12094–12103. doi: 10.1128/JVI.01730-08
7. Bosch D., Schots A., (2010). Plant glycans: friend or foe in vaccine development? Expert Rev. Vaccines 9 (8), 835–842. doi: 10.1586/erv.10.83
8. Bricault C. A., Kovacs J. M., Nkolola J. P., Yusim K., Giorgi E. E., Shields J. L.. (2015). A multivalent clade C HIV-1 Env trimer cocktail elicits a higher magnitude of neutralizing antibodies than any individual component. J. Virol. 89 (5), 2507–2519. doi: 10.1128/JVI.03331-14
9. Chapman R., Jongwe T. I., Douglass N., Chege G., Williamson A. L., (2017). Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice. PLoS One 12 (3), e0173352. doi: 10.1371/journal.pone.0173352
10. Chichester J. A., Jones R. M., Green B. J., Stow M., Miao F., Moonsammy G.. (2012). Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: a phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults. Viruses 4 (11), 3227–3244. doi: 10.3390/v4113227
11. Crooks E. T., Moore P. L., Franti M., Cayanan C. S., Zhu P., Jiang P.. (2007). A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120. Virology 366 (2), 245–262. doi: 10.1016/j.virol.2007.04.033
12. Crooks E. T., Osawa K., Tong T., Grimley S. L., Dai Y. D., Whalen R. G.. (2017). Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 Envelope glycoprotein trimers on neutralizing antibody induction. Virology 505, 193–209. doi: 10.1016/j.virol.2017.02.024
13. Crooks E. T., Tong T., Chakrabarti B., Narayan K., Georgiev I. S., Menis S.. (2015). Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog. 11 (5), e1004932. doi: 10.1371/journal.ppat.1004932
14. Crooks E. T., Tong T., Osawa K., Binley J. M., (2011). Enzyme digests eliminate nonfunctional Env from HIV-1 particle surfaces, leaving native Env trimers intact and viral infectivity unaffected. J. Virol. 85 (12), 5825–5839. doi: 10.1128/JVI.00154-11
15. Cummings J. F., Guerrero M. L., Moon J. E., Waterman P., Nielsen R. K., Jefferson S.. (2014). Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1 dose-escalation study in healthy adults. Vaccine 32 (19), 2251–2259. doi: 10.1016/j.vaccine.2013.10.017
16. D’Aoust M. A., Lavoie P. O., Couture M. M., Trepanier S., Guay J. M., Dargis M.. (2008). Influenza virus-like particles produced by transient expression in Nicotiana benthamiana induce a protective immune response against a lethal viral challenge in mice. Plant Biotechnol. J. 6 (9), 930–940. doi: 10.1111/j.1467-7652.2008.00384.x
17. D’Aoust M. A., Couture M. M., Lavoie P. O., Vezina L. P., (2011). Virus Like Particle Production In Plants. https://www.lens.org/lens/patent/WO_2012_083445_A1. E. P. Organisation.
18. Doria-Rose N. A., Klein R. M., Daniels M. G., O'Dell S., Nason M., Lapedes A.. (2010). Breadth of human immunodeficiency virus-specific neutralizing activity in sera: clustering analysis and association with clinical variables. J. Virol. 84 (3), 1631–1636. doi: 10.1128/JVI.01482-09
19. Doria-Rose N. A., Klein R. M., Manion M. M., O'Dell S., Phogat A., Chakrabarti B.. (2009). Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J. Virol. 83 (1), 188–199. doi: 10.1128/JVI.01583-08
20. Doria-Rose N. A., Schramm C. A., Gorman J., Moore P. L., Bhiman J. N., DeKosky B. J.. (2014). Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509 (7498), 55–62. doi: 10.1038/nature13036
21. Durrani Z., McInerney T. L., McLain L., Jones T., Bellaby T., Brennan F. R.. (1998). Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization. J. Immunol. Methods 220 (1-2), 93–103. doi: 10.1016/S0022-1759(98)00145-8
22. Euler Z., van Gils M. J., Bunnik E. M., Phung P., Schweighardt B., Wrin T.. (2010). Cross-reactive neutralizing humoral immunity does not protect from HIV type 1 disease progression. J. Infect. Dis. 201 (7), 1045–1053. doi: 10.1086/651144
23. Fischer W., Perkins S., Theiler J., Bhattacharya T., Yusim K., Funkhouser R.. (2007). Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat. Med. 13 (1), 100–106. doi: 10.1038/nm1461
24. Georgiev I. S., Joyce M. G., Yang Y., Sastry M., Zhang B., Baxa U.. (2015). Single-Chain Soluble BG505.SOSIP gp140 Trimers as Structural and Antigenic Mimics of Mature Closed HIV-1 Env. J. Virol. 89 (10), 5318–5329. doi: 10.1128/JVI.03451-14
25. Gray E. S., Madiga M. C., Hermanus T., Moore P. L., Wibmer C. K., Tumba N. L.. (2011). The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. J. Virol. 85 (10), 4828–4840. doi: 10.1128/JVI.00198-11
26. Hamorsky K. T., Kouokam J. C., Jurkiewicz J. M., Nelson B., Moore L. J., Husk A. S.. (2015). N-glycosylation of cholera toxin B subunit in Nicotiana benthamiana: impacts on host stress response, production yield and vaccine potential. Sci. Rep. 5, 8003. doi: 10.1038/srep08003
27. Haynes B. F., Gilbert P. B., McElrath M. J., Zolla-Pazner S., Tomaras G. D., Alam S. M.. (2012). Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med 366 (14), 1275–1286. doi: 10.1056/NEJMoa1113425
28. Hefferon K., (2013). Plant-derived pharmaceuticals for the developing world. Biotechnol. J. 8 (10), 1193–1202. doi: 10.1002/biot.201300162
29. Hessell A. J., Rakasz E. G., Poignard P., Hangartner L., Landucci G., Forthal D N.. (2009). Broadly neutralizing human anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers. PLoS Pathog. 5 (5), e1000433. doi: 10.1371/journal.ppat.1000433
30. Horn M. E., Pappu K. M., Bailey M. R., Clough R. C., Barker M., Jilka J. M.. (2003). Advantageous features of plant-based systems for the development of HIV vaccines. J. Drug Target 11 (8-10), 539–545. doi: 10.1080/10611860410001669992
31. Howell S. H., (2013). Endoplasmic reticulum stress responses in plants. Annu. Rev. Plant Biol. 64, 477–499. doi: 10.1146/annurev-arplant-050312-120053
32. Hraber P., Seaman M. S., Bailer R. T., Mascola J. R., Montefiori D. C., Korber B. T., (2014). Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS 28 (2), 163–169. doi: 10.1097/QAD.0000000000000106
33. Jongwe T. I., Chapman R., Douglass N., Chetty S., Chege G., Williamson A. L., (2016). HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice. PLoS One 11 (7), e0159141. doi: 10.1371/journal.pone.0159141
34. Julien J. P., Lee J. H., Cupo A., Murin C. D., Derking R., Hoffenberg S.. (2013). Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc. Natl. Acad. Sci. U.S.A 110 (11), 4351–4356. doi: 10.1073/pnas.1217537110
35. Julien J. P., Lee J. H., Ozorowski G., Hua Y., Torrents de la Pena A., de Taeye S. W.. (2015). Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. Proc. Natl. Acad. Sci. U.S.A 112 (38), 11947–11952. doi: 10.1073/pnas.1507793112
36. Karlsson Hedestam G. B., Fouchier R. A., Phogat S., Burton D. R., Sodroski J., Wyatt R. T., (2008). The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Microbiol. 6 (2), 143–155. doi: 10.1038/nrmicro1819
37. Kessans S. A., Linhart M. D., Meador L. R., Kilbourne J., Hogue B. G., Fromme P.. (2016). Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles. PLoS One 11 (3), e0151842. doi: 10.1371/journal.pone.0151842
38. Kim T. G., Gruber A., Langridge W. H., (2004). HIV-1 gp120 V3 cholera toxin B subunit fusion gene expression in transgenic potato. Protein Expr. Purif. 37 (1), 196–202. doi: 10.1016/j.pep.2004.04.014
39. Kovacs J. M., Noeldeke E., Ha H. J., Peng H., Rits-Volloch S., Harrison S. C.. (2014). Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure. Proc. Natl. Acad. Sci. U.S.A 111 (52), 18542–18547. doi: 10.1073/pnas.1422269112
40. Landais E., Huang X., Havenar-Daughton C., Murrell B., Price M. A., Wickramasinghe L.. (2016). Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort. PLoS Pathog. 12 (1), e1005369. doi: 10.1371/journal.ppat.1005369
41. Landry N., Ward B. J., Trepanier S., Montomoli E., Dargis M., Lapini G.. (2010). Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. PLoS One 5 (12), e15559. doi: 10.1371/journal.pone.0015559
42. Li Y., Migueles S. A., Welcher B., Svehla K., Phogat A., Louder M. K.. (2007). Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat. Med. 13 (9), 1032–1034. doi: 10.1038/nm1624
43. Liao H. X., Bonsignori M., Alam S. M., McLellan J. S., Tomaras G. D., Moody M. A.. (2013). Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity 38 (1), 176–186. doi: 10.1016/j.immuni.2012.11.011
44. Longo N. S., Sutton M. S., Shiakolas A. R., Guenaga J., Jarosinski M. C., Georgiev I. S.. (2016). Multiple antibody lineages in one donor target the glycan-V3 supersite of the HIV-1 envelope glycoprotein and display a preference for quaternary binding. J. Virol. 90, 10574–10586. doi: 10.1128/JVI.01012-16
45. Ma J. K., Christou P., Chikwamba R., Haydon H., Paul M., Ferrer M. P.. (2013). Realising the value of plant molecular pharming to benefit the poor in developing countries and emerging economies. Plant Biotechnol. J. 11 (9), 1029–1033. doi: 10.1111/pbi.12127
46. Maclean J., Koekemoer M., Olivier A. J., Stewart D., Hitzeroth I. I., Rademacher R.. (2007). Optimization of human papillomavirus type 16 (HPV-16) L1 expression in plants: comparison of the suitability of different HPV-16 L1 gene variants and different cell-compartment localization. J. Gen. Virol. 88, 1460–1469. doi: 10.1099/vir.0.82718-0
47. Madhun A. S., Haaheim L. R., Nostbakken J. K., Ebensen T., Chichester J., Yusibov V.. (2011). Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice. Vaccine 29 (31), 4973–4982. doi: 10.1016/j.vaccine.2011.04.094
48. Margolin E., (2017). Development of a transient expression platform for the production of soluble HIV-1 subtype C envelope mimetics in plants PhD thesis. Cape Town, South Africa: University of Cape Town, 54–55.
49. Marusic C., Rizza P., Lattanzi L., Mancini C., Spada M., Belardelli F.. (2001). Chimeric plant virus particles as immunogens for inducing murine and human immune responses against human immunodeficiency virus type 1. J. Virol. 75 (18), 8434–8439. doi: 10.1128/JVI.75.18.8434-8439.2001
50. Mascola J. R., Lewis M. G., Stiegler G., Harris D., VanCott T. C., Hayes D.. (1999). Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J. Virol. 73 (5), 4009–4018.
51. McCoy L. E., McKnight A., (2017). Lessons learned from humoral responses of HIV patients. Curr. Opin. HIV AIDS 12 (3), 195–202. doi: 10.1097/COH.0000000000000361
52. Medlock J., Pandey A., Parpia A. S., Tang A., Skrip L. A., Galvani A. P., (2017). Effectiveness of UNAIDS targets and HIV vaccination across 127 countries. Proc. Natl. Acad. Sci. U.S.A. 114, 4017–4022. doi: 10.1073/pnas.1620788114
53. Montefiori D. C., (2005). Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays. Curr. Protoc. Immunol. Chapter 12: Unit 12, 11. doi: 10.1002/0471142735.im1211s64
54. Moore P. L., Gray E. S., Sheward D., Madiga M., Ranchobe N., Lai Z.. (2011). Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. J. Virol. 85 (7), 3128–3141. doi: 10.1128/JVI.02658-10
55. Moore P. L., Sheward D., Nonyane M., Ranchobe N., Hermanus T., Gray E. S.. (2013). Multiple pathways of escape from HIV broadly cross-neutralizing V2-dependent antibodies. J. Virol. 87 (9), 4882–4894. doi: 10.1128/JVI.03424-12
56. Mortimer E., Maclean J. M., Mbewana S., Buys A., Williamson A. L., Hitzeroth I. I.. (2012). Setting up a platform for plant-based influenza virus vaccine production in South Africa. BMC Biotechnol. 12, 14. doi: 10.1186/1472-6750-12-14
57. Parren P. W., Marx P. A., Hessell A. J., Luckay A., Harouse J., Cheng-Mayer C.. (2001). Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J. Virol. 75 (17), 8340–8347. doi: 10.1128/JVI.75.17.8340-8347.2001
58. Rerks-Ngarm S., Pitisuttithum P., Nitayaphan S., Kaewkungwal J., Chiu J., Paris R.. (2009). Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med 361 (23), 2209–2220. doi: 10.1056/NEJMoa0908492
59. Ringe R. P., Sanders R. W., Yasmeen A., Kim H. J., Lee J. H., Cupo A.. (2013). Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc. Natl. Acad. Sci. U.S.A 110 (45), 18256–18261. doi: 10.1073/pnas.1314351110
60. Robb M. L., Rerks-Ngarm S., Nitayaphan S., Pitisuttithum P., Kaewkungwal J., Kunasol P.. (2012). Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144. Lancet Infect. Dis. 12 (7), 531–537. doi: 10.1016/S1473-3099(12)70088-9
61. Rosenberg Y., Sack M., Montefiori D., Forthal D., Mao L., Hernandez-Abanto S.. (2013). Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems. PLoS One 8 (3), e58724. doi: 10.1371/journal.pone.0058724
62. Sanders R. W., Derking R., Cupo A., Julien J. P., Yasmeen A., de Val N.. (2013). 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. 9 (9), e1003618. doi: 10.1371/journal.ppat.1003618
63. Sanders R. W., Moore J. P., (2017). Native-like Env trimers as a platform for HIV-1 vaccine design. Immunol. Rev. 275 (1), 161–182. doi: 10.1111/imr.12481
64. Sather D. N., Armann J., Ching L. K., Mavrantoni A., Sellhorn G., Caldwell Z.. (2009). Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J. Virol. 83 (2), 757–769. doi: 10.1128/JVI.02036-08
65. Seaman M. S., Janes H., Hawkins N., Grandpre L. E., Devoy C., Giri A.. (2010). Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J. Virol. 84 (3), 1439–1452. doi: 10.1128/JVI.02108-09
66. Shao Y., Williamson C., (2012). The HIV-1 epidemic: low- to middle-income countries. Cold Spring Harb. Perspect. Med. 2 (3), a007187. doi: 10.1101/cshperspect.a007187.
67. Sharma S. K., de Val N., Bale S., Guenaga J., Tran K., Feng Y.. (2015). Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Rep. 11 (4), 539–550. doi: 10.1016/j.celrep.2015.03.047
68. Shingai M., Donau O. K., Plishka R. J., Buckler-White A., Mascola J. R., Nabel G. J.. (2014). Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques. J. Exp Med 211 (10), 2061–2074. doi: 10.1084/jem.20132494
69. Shoji Y., Bi H., Musiychuk K., Rhee A., Horsey A., Roy G.. (2009a). Plant-derived hemagglutinin protects ferrets against challenge infection with the A/Indonesia/05/05 strain of avian influenza. Vaccine 27 (7), 1087–1092. doi: 10.1016/j.vaccine.2008.11.108
70. Shoji Y., Chichester J. A., Bi H., Musiychuk K., de la Rosa P., Goldschmidt L.. (2008). Plant-expressed HA as a seasonal influenza vaccine candidate. Vaccine 26 (23), 2930–2934. doi: 10.1016/j.vaccine.2008.03.045
71. Shoji Y., Farrance C. E., Bautista J., Bi H., Musiychuk K., Horsey A.. (2012). A plant-based system for rapid production of influenza vaccine antigens. Influenza Other Respir Viruses 6 (3), 204–210. doi: 10.1111/j.1750-2659.2011.00295.x
72. Shoji Y., Farrance C. E., Bi H., Shamloul M., Green B., Manceva S.. (2009b). Immunogenicity of hemagglutinin from A/Bar-headed Goose/Qinghai/1A/05 and A/Anhui/1/05 strains of H5N1 influenza viruses produced in Nicotiana benthamiana plants. Vaccine 27 (25-26), 3467–3470. doi: 10.1016/j.vaccine.2009.01.051
73. Simek M. D., Rida W., Priddy F. H., Pung P., Carrow E., Laufer D. S.. (2009). 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. 83 (14), 7337–7348. doi: 10.1128/JVI.00110-09
74. Sok D., van Gils M. J., Pauthner M., Julien J. P., Saye-Francisco K. L., Hsueh J.. (2014). Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc. Natl. Acad. Sci. U.S.A 111 (49), 17624–17629. doi: 10.1073/pnas.1415789111
75. Stephenson K. E., D'Couto H. T., Barouch D. H., (2016). New concepts in HIV-1 vaccine development. Curr. Opin. Immunol. 41, 39–46. doi: 10.1016/j.coi.2016.05.011
76. Sutter G., Moss B., (1992). Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc. Natl. Acad. Sci. U.S.A 89 (22), 10847–10851. doi: 10.1073/pnas.89.22.10847
77. Tong T., Crooks E. T., Osawa K., Binley J. M., (2012). HIV-1 virus-like particles bearing pure env trimers expose neutralizing epitopes but occlude nonneutralizing epitopes. J. Virol. 86 (7), 3574–3587. doi: 10.1128/JVI.06938-11
78. Tong T., Crooks E. T., Osawa K., Robinson J. E., Barnes M., Apetrei C.. (2014). Multi-parameter exploration of HIV-1 virus-like particles as neutralizing antibody immunogens in guinea pigs, rabbits and macaques. Virology 456-457, 55–69. doi: 10.1016/j.virol.2014.03.015
79. van Diepen M. T., Chapman R., Douglass N., Galant S., Moore P. L., Margolin E.. (2019). Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. J. Virol. 93 (8), e02155–18. doi: 10.1128/JVI.02155-18
80. van Diepen M. T., Chapman R., Moore P. L., Margolin E., Hermanus T., Morris L.. (2018). The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. PLoS One 13 (12), e0208310. doi: 10.1371/journal.pone.0208310
81. Walker L. M., Huber M., Doores K. J., Falkowska E., Pejchal R., Julien J. P.. (2011). Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477 (7365), 466–470. doi: 10.1038/nature10373
82. Walker L. M., Phogat S. K., Chan-Hui P. Y., Wagner D., Phung P., Goss J. L.. (2009). Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326 (5950), 285–289. doi: 10.1126/science.1178746
83. Wilbers R. H., Westerhof L. B., van Raaij D. R., van Adrichem M., Prakasa A. D., Lozano-Torres J. L.. (2016). Co-expression of the protease furin in Nicotiana benthamiana leads to efficient processing of latent transforming growth factor-beta1 into a biologically active protein. Plant Biotechnol. J. 14 (8), 1695–1704. doi: 10.1111/pbi.12530
84. Williamson C., Morris L., Maughan M. F., Ping L. H., Dryga S. A., Thomas R.. (2003). Characterization and selection of HIV-1 subtype C isolates for use in vaccine development. AIDS Res. Hum. Retroviruses 19 (2), 133–144. doi: 10.1089/088922203762688649
85. Yusibov V., Kushnir N., Streatfield S. J., (2015). Advances and challenges in the development and production of effective plant-based influenza vaccines. Expert Rev. Vaccines 14 (4), 519–535. doi: 10.1586/14760584.2015.989988
86. Yusibov V., Modelska A., Steplewski K., Agadjanyan M., Weiner D., Hooper D. C.. (1997). Antigens produced in plants by infection with chimeric plant viruses immunize against rabies virus and HIV-1. Proc. Natl. Acad. Sci. U.S.A 94 (11), 5784–5788. doi: 10.1073/pnas.94.11.5784
87. Zabel F., Kundig T. M., Bachmann M. F., (2013). Virus-induced humoral immunity: on how B cell responses are initiated. Curr. Opin. Virol. 3 (3), 357–362. doi: 10.1016/j.coviro.2013.05.004
88. Zambonelli C., Dey A. K., Hilt S., Stephenson S., Go E. P., Clark D. F.. (2016). Generation and Characterization of a Bivalent HIV-1 Subtype C gp120 Protein Boost for Proof-of-Concept HIV Vaccine Efficacy Trials in Southern Africa. PLoS One 11 (7), e0157391. doi: 10.1371/journal.pone.0157391