Process monitoring framework for cross-flow diafiltration-based virus-like particle disassembly: Tracing product properties and filtration performance.
cross-flow filtration
disassembly
downstream processing
process analytical technology
tangential flow filtration
virus-like particles
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
09
02
2022
received:
05
12
2021
accepted:
10
02
2022
pubmed:
17
2
2022
medline:
18
5
2022
entrez:
16
2
2022
Statut:
ppublish
Résumé
Virus-like particles (VLPs) are an emerging biopharmaceutical modality with great potential as a platform technology. VLPs can be applied as gene therapy vectors and prophylactic or therapeutic vaccines. For non-enveloped VLPs, recombinant production of the protein subunits leads to intracellular self-assembly. The subsequent purification process includes VLP dis- and reassembly which aim at removing encapsulated impurities and improving particle properties. Filtration-based separation and processing has proven successful for VLPs but requires large product quantities and laborious experiments in early development stages. Both challenges can be tackled by implementation of process analytical technology (PAT) to efficiently obtain extensive process information. In this study, an existing PAT setup was extended to comprehensively monitor the diafiltration-based disassembly of hepatitis B core antigen (HBcAg) VLPs. Process-related signals were monitored in-line, while product-related signals, such as ultraviolet light (UV) spectra as well as static and dynamic light scattering (SLS and DLS), were monitored on-line. The applicability of the sensors for disassembly monitoring was evaluated under varying processing conditions. HBcAg VLP subunit concentrations were accurately predicted based on UV data using ordinary and partial least squares regression models (Q
Substances chimiques
Hepatitis B Core Antigens
0
Vaccines, Virus-Like Particle
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1522-1538Informations de copyright
© 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
Références
Andersen, C. M., & Bro, R. (2010). Variable selection in regression-A tutorial. Journal of Chemometrics, 24(11-12), 728-737. https://doi.org/10.1002/cem.1360
Ashley, C. E., Carnes, E. C., Phillips, G. K., Durfee, P. N., Buley, M. D., Lino, C. A., Padilla, D. P., Phillips, B., Carter, M. B., Willman, C. L., Brinker, C. J., Caldeira Jdo, C., Chackerian, B., Wharton, W., & Peabody, D. S. (2011). Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles. ACS Nano, 5(7), 5729-5745. https://doi.org/10.1021/nn201397z
Ausar, S. F., Foubert, T. R., Hudson, M. H., Vedvick, T. S., & Middaugh, C. R. (2006). Conformational stability and disassembly of Norwalk virus-like particles. Journal of Biological Chemistry, 281(28), 19478-19488. https://doi.org/10.1074/jbc.M603313200
Bohren, C. F., & Huffman, D. R. (2004). Absorption and scattering of light by small particles. Wiley-VCH Verlag GmbH & Co. KGaA. https://doi.org/10.1002/9783527618156
Carreira, A., Menéndez, M., Reguera, J., Almendral, J. M., & Mateu, M. G. (2004). In vitro disassembly of a parvovirus capsid and effect on capsid stability of heterologous peptide insertions in surface loops. Journal of Biological Chemistry, 279(8), 6517-6525. https://doi.org/10.1074/jbc.M307662200
Carvalho, S. B., Silva, R. J. S., Moleirinho, M. G., Cunha, B., Moreira, A. S., Xenopoulos, A., Alves, P. M., Carrondo, M. J. T., & Peixoto, C. (2019). Membrane-based approach for the downstream processing of influenza virus-like particles. Biotechnology Journal, 14(8), 1800570. https://doi.org/10.1002/biot.201800570
Ceres, P., & Zlotnick, A. (2002). Weak protein−protein interactions are sufficient to drive assembly of hepatitis B virus capsids. Biochemistry, 41(39), 11525-11531. https://doi.org/10.1021/bi0261645
Cerqueira, C., Thompson, C. D., Day, P. M., Pang, Y.-Y. S., Lowy, D. R., & Schiller, J. T. (2017). Efficient production of papillomavirus gene delivery vectors in defined in vitro reactions. Molecular Therapy-Methods & Clinical Development, 5, 165-179. https://doi.org/10.1016/j.omtm.2017.04.005
Chandramohan, D., Zongo, I., Sagara, I., Cairns, M., Yerbanga, R.-S., Diarra, M., Nikièma, F., Tapily, A., Sompougdou, F., Issiaka, D., Zoungrana, C., Sanogo, K., Haro, A., Kaya, M., Sienou, A. A., Traore, S., Mahamar, A., Thera, I., Diarra, K., … Greenwood, B. (2021). Seasonal malaria vaccination with or without seasonal malaria chemoprevention. New England Journal of Medicine, 385(11), 1005-1017. https://doi.org/10.1056/NEJMoa2026330
Chu, K.-B., Kang, H.-J., Yoon, K.-W., Lee, H.-A., Moon, E.-K., Han, B.-K., & Quan, F.-S. (2021). Influenza virus-like particle (VLP) vaccines expressing the SARS-CoV-2 S glycoprotein, S1, or S2 domains. Vaccines, 9(8), 920. https://doi.org/10.3390/vaccines9080920
Deep, K., Singh, K. P., Kansal, M. L., & Mohan, C. (2009). A real coded genetic algorithm for solving integer and mixed integer optimization problems. Applied Mathematics and Computation, 212(2), 505-518. https://doi.org/10.1016/j.amc.2009.02.044
de Jong, S. (1993). SIMPLS: An alternative approach to partial least squares regression. Chemometrics and Intelligent Laboratory Systems, 18(3), 251-263. https://doi.org/10.1016/0169-7439(93)85002-X
Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S., Wilkins, M. R., Appel, R. D., & Bairoch, A. (2005). Protein identification and analysis tools on the ExPASy server. In J. M. Walker (Ed.), The proteomics protocols handbook (pp. 571-607). Humana Press. https://doi.org/10.1385/1-59259-890-0:571
Großhans, S., Rüdt, M., Sanden, A., Brestrich, N., Morgenstern, J., Heissler, S., & Hubbuch, J. (2018). In-line Fourier-transform infrared spectroscopy as a versatile process analytical technology for preparative protein chromatography. Journal of Chromatography A, 1547, 37-44. https://doi.org/10.1016/j.chroma.2018.03.005
Grzenia, D. L., Carlson, J. O., & Wickramasinghe, S. R. (2008). Tangential flow filtration for virus purification. Journal of Membrane Science, 321(2), 373-380. https://doi.org/10.1016/j.memsci.2008.05.020
Hansen, S. K., Jamali, B., & Hubbuch, J. (2013). Selective high throughput protein quantification based on UV absorption spectra. Biotechnology and Bioengineering, 110(2), 448-460. https://doi.org/10.1002/bit.24712
Hartzell, E. J., Lieser, R. M., Sullivan, M. O., & Chen, W. (2020). Modular hepatitis B virus-like particle platform for biosensing and drug delivery. ACS Nano, 14(10), 12642-12651. https://doi.org/10.1021/acsnano.9b08756
Hassan, P. A., Rana, S., & Verma, G. (2015). Making sense of Brownian motion: Colloid characterization by dynamic light scattering. Langmuir: The ACS Journal of Surfaces and Colloids, 31(1), 3-12. https://doi.org/10.1021/la501789z
Hillebrandt, N., Vormittag, P., Bluthardt, N., Dietrich, A., & Hubbuch, J. (2020). Integrated process for capture and purification of virus-like particles: Enhancing process performance by cross-flow filtration. Frontiers in Bioengineering and Biotechnology, 8, 489. https://doi.org/10.3389/fbioe.2020.00489
Hillebrandt, N., Vormittag, P., Dietrich, A., Wegner, C. H., & Hubbuch, J. (2021). Process development for cross-flow diafiltration-based VLP disassembly: A novel high-throughput screening approach. Biotechnology and Bioengineering, 118(10), 3926-3940. https://doi.org/10.1002/bit.27868
Holmes, K., Shepherd, D. A., Ashcroft, A. E., Whelan, M., Rowlands, D. J., & Stonehouse, N. J. (2015). Assembly pathway of hepatitis B core virus-like particles from genetically fused dimers. Journal of Biological Chemistry, 290(26), 16238-16245. https://doi.org/10.1074/jbc.M114.622035
ICH Expert Working Group. (2009). Q8(R2) guideline-Pharmaceutical development. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. https://database.ich.org/sites/default/files/Q8%28R2%29Guideline.pdf
ICH Expert Working Group. (2012). Q11 guideline-Development and manufacture of drug substances. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. https://database.ich.org/sites/default/files/Q11Guideline.pdf
Kalbfuss, B., Genzel, Y., Wolff, M., Zimmermann, A., Morenweiser, R., & Reichl, U. (2007). Harvesting and concentration of human influenza A virus produced in serum-free mammalian cell culture for the production of vaccines. Biotechnology and Bioengineering, 97(1), 73-85. https://doi.org/10.1002/bit.21139
Karpenko, L. I., Ivanisenko, V. A., Pika, I. A., Chikaev, N. A., Eroshkin, A. M., Veremeiko, T. A., & Ilyichev, A. A. (2000). Insertion of foreign epitopes in HBcAg: How to make the chimeric particle assemble. Amino Acids, 18(4), 329-337. https://doi.org/10.1007/s007260070072
Kaufmann, A. M., Nieland, J. D., Jochmus, I., Baur, S., Friese, K., Gabelsberger, J., Gieseking, F., Gissmann, L., Glasschröder, B., Grubert, T., Hillemanns, P., Höpfl, R., Ikenberg, H., Schwarz, J., Karrasch, M., Knoll, A., Küppers, V., Lechmann, M., Lelle, R. J., … Schneider, A. (2007). Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3). International Journal of Cancer, 121(12), 2794-2800. https://doi.org/10.1002/ijc.23022
Kessler, W. (2006). Multivariate datenanalyse. Wiley. https://doi.org/10.1002/9783527610037
Kingston, N. J., Kurtovic, L., Walsh, R., Joe, C., Lovrecz, G., Locarnini, S., Beeson, J. G., & Netter, H. J. (2019). Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein. Vaccine, 37(12), 1674-1684. https://doi.org/10.1016/j.vaccine.2019.01.056
Klamp, T., Schumacher, J., Huber, G., Kühne, C., Meissner, U., Selmi, A., Hiller, T., Kreiter, S., Markl, J., Türeci, Ö., & Sahin, U. (2011). Highly specific auto-antibodies against claudin-18 isoform 2 induced by a chimeric HBcAg virus-like particle vaccine kill tumor cells and inhibit the growth of lung metastases. Cancer Research, 71(2), 516-527. https://doi.org/10.1158/0008-5472.CAN-10-2292
Kurnik, R. T., Yu, A. W., Blank, G. S., Burton, A. R., Smith, D., Athalye, A. M., & van Reis, R. (1995). Buffer exchange using size exclusion chromatography, countercurrent dialysis, and tangential flow filtration: Models, development, and industrial application. Biotechnology and Bioengineering, 45(2), 149-157. https://doi.org/10.1002/bit.260450209
Lee, K. W., & Tan, W. S. (2008). Recombinant hepatitis B virus core particles: Association, dissociation and encapsidation of green fluorescent protein. Journal of Virological Methods, 151(2), 172-180. https://doi.org/10.1016/j.jviromet.2008.05.025
Leung, A. B., Suh, K. I., & Ansari, R. R. (2006). Particle-size and velocity measurements in flowing conditions using dynamic light scattering. Applied Optics, 45(10), 2186-2190. https://doi.org/10.1364/AO.45.002186
Liew, M. W. O., Chuan, Y. P., & Middelberg, A. P. J. (2012). Reactive diafiltration for assembly and formulation of virus-like particles. Biochemical Engineering Journal, 68, 120-128. https://doi.org/10.1016/j.bej.2012.07.009
Lin, S.-Y., Chiu, H.-Y., Chiang, B.-L., & Hu, Y.-C. (2015). Development of EV71 virus-like particle purification processes. Vaccine, 33(44), 5966-5973. https://doi.org/10.1016/j.vaccine.2015.04.077
Mach, H., & Middaugh, C. R. (1994). Simultaneous monitoring of the environment of tryptophan, tyrosine, and phenylalanine residues in proteins by near-ultraviolet second-derivative spectroscopy. Analytical Biochemistry, 222(2), 323-331. https://doi.org/10.1006/abio.1994.1499
Mach, H., Volkin, D. B., Troutman, R. D., Wang, B., Luo, Z., Jansen, K. U., & Shi, L. (2006). Disassembly and reassembly of yeast-derived recombinant human papillomavirus virus-like particles (HPV VLPs). Journal of Pharmaceutical Sciences, 95(10), 2195-2206. https://doi.org/10.1002/jps.20696
McCarthy, M. P., White, W. I., Palmer-Hill, F., Koenig, S., & Suzich, J. A. (1998). Quantitative disassembly and reassembly of human papillomavirus type 11 viruslike particles in vitro. Journal of Virology, 72(1), 32-41. https://doi.org/10.1128/JVI.72.1.32-41.1998
Mellado, M. C. M., Mena, J. A., Lopes, A., Ramírez, O. T., Carrondo, M. J. T., Palomares, L. A., & Alves, P. M. (2009). Impact of physicochemical parameters on in vitro assembly and disassembly kinetics of recombinant triple-layered rotavirus-like particles. Biotechnology and Bioengineering, 104(4), https://doi.org/10.1002/bit.22430
Mohsen, M., Gomes, A., Vogel, M., & Bachmann, M. (2018). Interaction of viral capsid-derived virus-like particles (VLPs) with the innate immune system. Vaccines, 6(3), 37. https://doi.org/10.3390/vaccines6030037
Moleirinho, M. G., Rosa, S., Carrondo, M., Silva, R., Hagner-McWhirter, Å., Ahlén, G., Lundgren, M., Alves, P. M., & Peixoto, C. (2018). Clinical-grade oncolytic adenovirus purification using polysorbate 20 as an alternative for cell lysis. Current Gene Therapy, 18(6), 366-374. https://doi.org/10.2174/1566523218666181109141257
Negrete, A., Pai, A., & Shiloach, J. (2014). Use of hollow fiber tangential flow filtration for the recovery and concentration of HIV virus-like particles produced in insect cells. Journal of Virological Methods, 195, 240-246. https://doi.org/10.1016/j.jviromet.2013.10.017
Neirynck, S., Deroo, T., Saelens, X., Vanlandschoot, P., Jou, W. M., & Fiers, W. (1999). A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nature Medicine, 5(10), 1157-1163. https://doi.org/10.1038/13484
Newman, M., Suk, F.-M., Cajimat, M., Chua, P. K., & Shih, C. (2003). Stability and morphology comparisons of self-assembled virus-like particles from wild-type and mutant human hepatitis B virus capsid proteins. Journal of Virology, 77(24), 12950-12960. https://doi.org/10.1128/JVI.77.24.12950-12960.2003
Nilsson, J., de Jong, S., & Smilde, A. K. (1997). Multiway calibration in 3D QSAR. Journal of Chemometrics, 11(6), 511-524. https://doi.org/10.1002/(SICI)1099-128X(199711/12)11:6%3C511::AID-CEM488%3E3.0.CO;2-W
Palladini, A., Thrane, S., Janitzek, C. M., Pihl, J., Clemmensen, S. B., de Jongh, W. A., Clausen, T. M., Nicoletti, G., Landuzzi, L., Penichet, M. L., Balboni, T., Ianzano, M. L., Giusti, V., Theander, T. G., Nielsen, M. A., Salanti, A., Lollini, P. L., Nanni, P., & Sander, A. F. (2018). Virus-like particle display of HER2 induces potent anti-cancer responses. Oncoimmunology, 7(3), e1408749. https://doi.org/10.1080/2162402X.2017.1408749
Peixoto, C., Sousa, M. F. Q., Silva, A. C., Carrondo, M. J. T., & Alves, P. M. (2007). Downstream processing of triple layered rotavirus like particles. Journal of Biotechnology, 127(3), 452-461. https://doi.org/10.1016/j.jbiotec.2006.08.002
Petrovskis, I., Lieknina, I., Dislers, A., Jansons, J., Bogans, J., Akopjana, I., Zakova, J., & Sominskaya, I. (2021). Production of the HBc protein from different HBV genotypes in E. coli. Use of reassociated HBc VLPs for packaging of ss- and dsRNA. Microorganisms, 9(2), 283. https://doi.org/10.3390/microorganisms9020283
Phillips, A. T., & Signs, M. W. (2004). Desalting, concentration, and buffer exchange by dialysis and ultrafiltration. Current Protocols in Protein Science, 38(1), 1-15. https://doi.org/10.1002/0471140864.ps0404s38
Porterfield, J. Z., & Zlotnick, A. (2010). A simple and general method for determining the protein and nucleic acid content of viruses by UV absorbance. Virology, 407(2), 281-288. https://doi.org/10.1016/j.virol.2010.08.015
Porterfield, J. Z., Dhason, M. S., Loeb, D. D., Nassal, M., Stray, S. J., & Zlotnick, A. (2010). Full-length hepatitis B virus core protein packages viral and heterologous RNA with similarly high levels of cooperativity. Journal of Virology, 84(14), 7174-7184. https://doi.org/10.1128/JVI.00586-10
Ragone, R., Colonna, G., Balestrieri, C., Servillo, L., & Irace, G. (1984). Determination of tyrosine exposure in proteins by second-derivative spectroscopy. Biochemistry, 23(8), 1871-1875. https://doi.org/10.1021/bi00303a044
Roldão, A., Mellado, M. C. M., Lima, J. C., Carrondo, M. J. T., Alves, P. M., & Oliveira, R. (2012). On the effect of thermodynamic equilibrium on the assembly efficiency of complex multi-layered virus-like particles (VLP): The case of rotavirus VLP. PLoS Computational Biology, 8(2), e1002367. https://doi.org/10.1371/journal.pcbi.1002367
Rolinger, L., Rüdt, M., Diehm, J., Chow-Hubbertz, J., Heitmann, M., Schleper, S., & Hubbuch, J. (2020). Multi-attribute PAT for UF/DF of proteins-Monitoring concentration, particle sizes, and buffer exchange. Analytical and Bioanalytical Chemistry, 412(9), 2123-2136. https://doi.org/10.1007/s00216-019-02318-8
Rolinger, L., Rüdt, M., & Hubbuch, J. (2021). A multisensor approach for improved protein A load phase monitoring by conductivity-based background subtraction of UV spectra. Biotechnology and Bioengineering, 118(2), 905-917. https://doi.org/10.1002/bit.27616
Rüdt, M., Vormittag, P., Hillebrandt, N., & Hubbuch, J. (2019). Process monitoring of virus-like particle reassembly by diafiltration with UV/Vis spectroscopy and light scattering. Biotechnology and Bioengineering, 116(6), 1366-1379. https://doi.org/10.1002/bit.26935
Rutgers, T., Gordon, D., Gathoye, A. M., Hollingdale, M., Hockmeyer, W., Rosenberg, M., & Wilde, M. de (1988). Hepatitis B surface antigen as carrier matrix for the repetitive epitope of the circumsporozoite protein of Plasmodium Falciparum. Nature Biotechnology, 6(9), 1065-1070. https://doi.org/10.1038/nbt0988-1065
Schumacher, J., Bacic, T., Staritzbichler, R., Daneschdar, M., Klamp, T., Arnold, P., Jägle, S., Türeci, Ö., Markl, J., & Sahin, U. (2018). Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide. Journal of Nanobiotechnology, 16(1), 39. https://doi.org/10.1186/s12951-018-0363-0
Sedlik, C., Saron, M. F., Sarraseca, J., Casal, I., & Leclerc, C. (1997). Recombinant parvovirus-like particles as an antigen carrier: A novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells. Proceedings of the National Academy of Sciences of the United States of America, 94(14), 7503-7508. https://doi.org/10.1073/pnas.94.14.7503
Shan, W., Zhang, D., Wu, Y., Lv, X., Hu, B., Zhou, X., Ye, S., Bi, S., Ren, L., & Zhang, X. (2018). Modularized peptides modified HBc virus-like particles for encapsulation and tumor-targeted delivery of doxorubicin. Nanomedicine: Nanotechnology, Biology and Medicine, 14(3), 725-734. https://doi.org/10.1016/j.nano.2017.12.002
Singh, S., & Zlotnick, A. (2003). Observed hysteresis of virus capsid disassembly is implicit in kinetic models of assembly. Journal of Biological Chemistry, 278(20), 18249-18255. https://doi.org/10.1074/jbc.M211408200
Stetefeld, J., McKenna, S. A., & Patel, T. R. (2016). Dynamic light scattering: A practical guide and applications in biomedical sciences. Biophysical Reviews, 8(4), 409-427. https://doi.org/10.1007/s12551-016-0218-6
Strods, A., Ose, V., Bogans, J., Cielens, I., Kalnins, G., Radovica, I., Kazaks, A., Pumpens, P., & Renhofa, R. (2015). Preparation by alkaline treatment and detailed characterisation of empty hepatitis B virus core particles for vaccine and gene therapy applications. Scientific Reports, 5(1), 11639. https://doi.org/10.1038/srep11639
Tan, T. K., Rijal, P., Rahikainen, R., Keeble, A. H., Schimanski, L., Hussain, S., Harvey, R., Hayes, J., Edwards, J. C., McLean, R. K., Martini, V., Pedrera, M., Thakur, N., Conceicao, C., Dietrich, I., Shelton, H., Ludi, A., Wilsden, G., Browning, C., … Townsend, A. R. (2021). A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses. Nature Communications, 12(1), 542. https://doi.org/10.1038/s41467-020-20654-7
Thomas, J. C. (1987). The determination of log normal particle size distributions by dynamic light scattering. Journal of Colloid and Interface Science, 117(1), 187-192. https://doi.org/10.1016/0021-9797(87)90182-2
U.S. Department of Health and Human Services-Food and Drug Administration. (2004). PAT-A framework for innovative pharmaceutical development, manufacuring, and quality assurance. Guidance for Industry. https://www.fda.gov/media/71012/download
van Rosmalen, M. G. M., Li, C., Zlotnick, A., Wuite, G. J. L., & Roos, W. H. (2018). Effect of dsDNA on the assembly pathway and mechanical strength of SV40 VP1 virus-like particles. Biophysical Journal, 115(9), 1656-1665. https://doi.org/10.1016/j.bpj.2018.07.044
Vicente, T., Mota, J. P. B., Peixoto, C., Alves, P. M., & Carrondo, M. J. T. (2011). Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: Current advances. Biotechnology Advances, 29(6), 869-878. https://doi.org/10.1016/j.biotechadv.2011.07.004
Wasalathanthri, D. P., Feroz, H., Puri, N., Hung, J., Lane, G., Holstein, M., Chemmalil, L., Both, D., Ghose, S., Ding, J., & Li, Z. J. (2020). Real-time monitoring of quality attributes by in-line Fourier transform infrared spectroscopic sensors at ultrafiltration and diafiltration of bioprocess. Biotechnology and Bioengineering, 117(12), 3766-3774. https://doi.org/10.1002/bit.27532
West, J. M., Feroz, H., Xu, X., Puri, N., Holstein, M., Ghose, S., Ding, J., & Li, Z. J. (2021). Process analytical technology for on-line monitoring of quality attributes during single-use ultrafiltration/diafiltration. Biotechnology and Bioengineering, 118(6), 2293-2300. https://doi.org/10.1002/bit.27741
Wickramasinghe, S. R., Kalbfuß, B., Zimmermann, A., Thom, V., & Reichl, U. (2005). Tangential flow microfiltration and ultrafiltration for human influenza A virus concentration and purification. Biotechnology and Bioengineering, 92(2), 199-208. https://doi.org/10.1002/bit.20599
Wold, S., Sjöström, M., & Eriksson, L. (2001). PLS-regression: A basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems, 58(2), 109-130. https://doi.org/10.1016/S0169-7439(01)00155-1
World Health Organization. (2021). Full evidence report on the RTS,S/AS01 malaria vaccine. https://www.who.int/initiatives/malaria-vaccine-implementation-programme
Wynne, S. A., Crowther, R. A., & Leslie, A. G. W. (1999). The crystal structure of the human hepatitis B virus capsid. Molecular Cell, 3(6), 771-780. https://doi.org/10.1016/S1097-2765(01)80009-5
Yang, Y., Shi, W., Abiona, O. M., Nazzari, A., Olia, A. S., Ou, L., Phung, E., Stephens, T., Tsybovsky, Y., Verardi, R., Wang, S., Werner, A., Yap, C., Ambrozak, D., Bylund, T., Liu, T., Nguyen, R., Wang, L., Zhang, B., … Kwong, P. D. (2021). Newcastle disease virus-like particles displaying prefusion-stabilized SARS-CoV-2 spikes elicit potent neutralizing responses. Vaccines, 9(2), 73. https://doi.org/10.3390/vaccines9020073
Yuan, W., & Parrish, C. R. (2001). Canine parvovirus capsid assembly and differences in mammalian and insect cells. Virology, 279(2), 546-557. https://doi.org/10.1006/viro.2000.0734
Zha, L., Chang, X., Zhao, H., Mohsen, M. O., Hong, L., Zhou, Y., Chen, H., Liu, X., Zhang, J., Li, D., Wu, K., Martina, B., Wang, J., Vogel, M., & Bachmann, M. F. (2021). Development of a vaccine against SARS-CoV-2 based on the receptor-binding domain displayed on virus-like particles. Vaccines, 9(4), 395. https://doi.org/10.3390/vaccines9040395
Zhang, Y., Song, S., Liu, C., Wang, Y., Xian, X., He, Y., Wang, J., Liu, F., & Sun, S. (2007). Generation of chimeric HBc proteins with epitopes in E.coli: Formation of virus-like particles and a potent inducer of antigen-specific cytotoxic immune response and anti-tumor effect in vivo. Cellular Immunology, 247(1), 18-27. https://doi.org/10.1016/j.cellimm.2007.07.003
Zhao, Q., Allen, M. J., Wang, Y., Wang, B., Wang, N., Shi, L., & Sitrin, R. D. (2012). Disassembly and reassembly improves morphology and thermal stability of human papillomavirus type 16 virus-like particles. Nanomedicine: Nanotechnology, Biology, and Medicine, 8(7), 1182-1189. https://doi.org/10.1016/j.nano.2012.01.007
Zhao, Q., Modis, Y., High, K., Towne, V., Meng, Y., Wang, Y., Alexandroff, J., Brown, M., Carragher, B., Potter, C. S., Abraham, D., Wohlpart, D., Kosinski, M., Washabaugh, M. W., & Sitrin, R. D. (2012). Disassembly and reassembly of human papillomavirus virus-like particles produces more virion-like antibody reactivity. Virology Journal, 9(1), 52. https://doi.org/10.1186/1743-422X-9-52
Zlotnick, A., Cheng, N., Conway, J. F., Booy, F. P., Steven, A. C., Stahl, S. J., & Wingfield, P. T. (1996). Dimorphism of hepatitis B virus capsids is strongly influenced by the C-terminus of the capsid protein. Biochemistry, 35(23), 7412-7421. https://doi.org/10.1021/bi9604800
Zobel-Roos, S., Mouellef, M., Siemers, C., & Strube, J. (2017). Process analytical approach towards quality controlled process automation for the downstream of protein mixtures by inline concentration measurements based on ultraviolet/visible light (UV/VIS) spectral analysis. Antibodies, 6(4), 24. https://doi.org/10.3390/antib6040024