Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity

Retrovirology

Rogier W. Sanders⁴  Andrew B. Ward³  John P. Moore⁴  David C. Montefiori¹  Celia LaBranche¹  Melissa Stunnenberg²  Thijs van Montfort²  Judith A. Burger²  Gabriel Ozorowski³  Kwinten Sliepen² 

[1] Department of Surgery, Duke University Medical Center, Durham 27710, NC, USA;Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands;Department of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery (CAVD), Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla 92037, CA, USA;Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York 10065, NY, USA

关键词: BG505;    SOSIP;    Vaccine;    Nanoparticles;    Ferritin;    Envelope glycoprotein;    HIV-1;   

Others  :  1230226
DOI  :  10.1186/s12977-015-0210-4

 received in 2015-07-06, accepted in 2015-09-22,  发布年份 2015

【 摘 要 】

Background

Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation.

Findings

We describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein trimers (BG505 SOSIP.664). Trimer-bearing nanoparticles were significantly more immunogenic than trimers in both mice and rabbits. Furthermore, rabbits immunized with the trimer-bearing nanoparticles induced significantly higher neutralizing antibody responses against most tier 1A viruses, and higher responses (but not significantly), to several tier 1B viruses and the autologous tier 2 virus than when the same trimers were delivered as soluble proteins.

Conclusions

This or other nanoparticle designs may be practical ways to improve the immunogenicity of envelope glycoprotein trimers.

【 授权许可】

   
2015 Sliepen et al.

【 图 表 】

Fig.1.

Fig.2.

【 参考文献 】

• [1]Van Gils MJ, Sanders RW. In vivo protection by broadly neutralizing HIV antibodies. Trends Microbiol. 2014; 22:550-551.
• [2]Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, Kim HJ, Blattner C, de la Peña AT, Korzun J, Golabek M, de los Reyes K, Ketas TJ, Vangils MJ, King CR, King CR, Wilson IA, Ward AB, Klasse PJ, Moore JP. 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:e1003618.
• [3]Lyumkis D, Julien J-P, de Val N, Cupo A, Potter CS, Klasse P-J, Burton DR, Sanders RW, Moore JP, Carragher B, Wilson IA, Ward AB. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science. 2013; 342:1484-1490.
• [4]Julien J-P, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, Klasse P-J, Burton DR, Sanders RW, Moore JP, Ward AB, Wilson IA. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science. 2013; 342:1477-1483.
• [5]Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, Huang J, Acharya P, Chuang G-Y, Ofek G, Stewart-Jones GBE, Stuckey J, Bailer RT, Joyce MG, Louder MK, Tumba N, Yang Y, Zhang B, Cohen MS, Haynes BF, Mascola JR, Morris L, Munro JB, Blanchard SC, Mothes W, Connors M, Kwong PD. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014; 514:455-461.
• [6]Blattner C, Lee JH, Sliepen K, Derking R, Falkowska E, de la Peña AT, Cupo A, Julien J-P, van Gils M, Lee PS, Peng W, Paulson JC, Poignard P, Burton DR, Moore JP, Sanders RW, Wilson IA, Ward AB. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 Interface on intact HIV-1 Env trimers. Immunity. 2014; 40:669-680.
• [7]Falkowska E, Le KM, Ramos A, Doores KJ, Lee J, Blattner C, Ramirez A, Derking R, VanGils MJ, Liang CH, Mcbride R, von Bredow B, Shivatare SS, Wu CY, Chan-Hui PY, Liu Y, Feizi T, Zwick MB, Koff WC, Seaman MS, Swiderek K, Moore JP, Evans D, Paulson JC, Wong CH, Ward AB, Wilson IA, Sanders RW, Poignard P, Burton DR. Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity. 2014; 40:657-668.
• [8]Huang J, Kang BH, Pancera M, Lee JH, Tong T, Feng Y, Imamichi H, Georgiev IS, Chuang G-Y, Druz A, Doria-Rose NA, Laub L, Sliepen K, van Gils MJ, de la Peña AT, Derking R, Klasse PJ, Migueles SA, Bailer RT, Alam M, Pugach P, Haynes BF, Wyatt RT, Sanders RW, Binley JM, Ward AB, Mascola JR, Kwong PD, Connors M. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature. 2014; 515:138-142.
• [9]Sanders RW, van Gils MJ, Derking R, Sok D, Ketas TJ, Burger JA, Ozorowski G, Cupo A, Simonich C, Goo L, Arendt H, Kim HJ, Lee JH, Pugach P, Williams M, Debnath G, Moldt B, van Breemen MJ, Isik G, Medina-Ramirez M, Back JW, Koff WC, Julien J-P, Rakasz EG, Seaman MS, Guttman M, Lee KK, Klasse PJ, LaBranche C, Schief WR et al.. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science. 2015; 349:aac4223.
• [10]Schiller J, Chackerian B. Why HIV virions have low numbers of envelope spikes: implications for vaccine development. PLoS Pathog. 2014; 10:e1004254.
• [11]Bachmann MF, Jennings GT. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol. 2010; 10:787-796.
• [12]Kanekiyo M, Wei C-J, Yassine HM, McTamney PM, Boyington JC, Whittle JRR, Rao SS, Kong W-P, Wang L, Nabel GJ. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013; 499:102-106.
• [13]Yassine HM, Boyington JC, McTamney PM, Wei C, Kanekiyo M, Kong W, Gallagher JR, Wang L, Zhang Y, Joyce MG, Lingwood D, Moin SM, Andersen H, Okuno Y, Rao SS, Harris AK, Kwong PD, Mascola JR, Nabel GJ, Graham BS. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015; 21:1065-1070.
• [14]Ringe RP, Sanders RW, Yasmeen A, Kim HJ, Lee JH, Cupo A, Korzun J, Derking R, van Montfort T, Julien J-P, Wilson IA, Klasse PJ, Ward AB, Moore JP. Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc Natl Acad Sci USA. 2013; 110:18256-18261.
• [15]Pugach P, Ozorowski G, Cupo A, Ringe R, Yasmeen A, de Val N, Derking R, Kim HJ, Korzun J, Golabek M, de Los Reyes K, Ketas TJ, Julien J-P, Burton DR, Wilson IA, Sanders RW, Klasse PJ, Ward AB, Moore JP. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J Virol. 2015; 89:3380-3395.
• [16]Anderson KP, Lucas C, Hanson CV, Londe HF, Izu A, Gregory T, Ammann A, Berman PW, Eichberg JW. Effect of dose and immunization schedule on immune response of baboons to recombinant glycoprotein 120 of HIV-1. J Infect Dis. 1989; 160:960-969.
• [17]Moon JJ, Suh H, Li AV, Ockenhouse CF, Yadava A, Irvine DJ. Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. Proc Natl Acad Sci USA. 2012; 109:1080-1085.
• [18]Bachmann MF, Zinkernagel RM. Neutralizing antiviral B cell responses. Annu Rev Immunol. 1997; 15:235-270.
• [19]Seaman MS, Janes H, Hawkins N, Grandpre LE, Devoy C, Giri A, Coffey RT, Harris L, Wood B, Daniels MG, Bhattacharya T, Lapedes A, Polonis VR, McCutchan FE, Gilbert PB, Self SG, Korber BT, Montefiori DC, Mascola JR. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol. 2010; 84:1439-1452.
• [20]Schrodinger LLC. The PyMOL molecular graphics system, Version 1.3r1. 2010.
• [21]Binley JM, Sanders RW, Master A, Cayanan CS, Wiley CL, Schiffner L, Travis B, Kuhmann S, Burton DR, Hu S, Olson WC, Moore JP. Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins. J Virol. 2002; 76:2606-2616.
• [22]Binley JM, Sanders RW, Clas B, Schuelke N, Master A, Guo Y, Kajumo F, Anselma DJ, Maddon PJ, Olson WC, Moore JP. A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol. 2000; 74:627-643.
• [23]Sanders RW, Vesanen M, Schuelke N, Master A, Schiffner L, Kalyanaraman R, Paluch M, Berkhout B, Maddon PJ, Olson WC, Lu M, Moore JP. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2002; 76:8875-8889.
• [24]Maraskovsky E, Schnurr M, Wilson NS, Robson NC, Boyle J, Drane D. Development of prophylactic and therapeutic vaccines using the ISCOMATRIX adjuvant. Immunol Cell Biol. 2009; 87:371-376.
• [25]Derking R, Ozorowski G, Sliepen K, Yasmeen A, Cupo A, Torres JL, Julien J-P, Lee JH, van Montfort T, de Taeye SW, Connors M, Burton DR, Wilson IA, Klasse P-J, Ward AB, Moore JP, Sanders RW. Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLOS Pathog. 2015; 11:e1004767.