A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
Abstract
:1. Introduction
- Fed-batch cultivation of HIV VLP producing HEK293F cells (human embryonic kidney 293 cells),
- Removal of cells and large cell debris by depth filtration,
- Initial purification by tangential flow filtration,
- Further VLP purification by anion exchange chromatography,
- Concentration by tangential flow filtration,
- Formulation of HIV VLPs by lyophilization.
2. Particle Friction-Based Model (PFBM) Developed by Schock [24]
3. Materials and Methods
3.1. HIV Mos-1-Gag VLP Production and Clarification
3.2. Tangential Flow Ultrafiltration
3.3. Analytics
3.3.1. Enzyme-Linked Immunosorbent Assay (ELISA)
3.3.2. Dynamic Light Scattering (DLS)
3.3.3. Zeta Potential
3.3.4. Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE)
3.3.5. Transmission Electron Microscopy (TEM)
3.4. Data Treatment and Estimation of Static Friction Coefficients
4. Results and Discussion
4.1. VLP Formation and Characterization
4.2. HIV VLP TFF Trials
4.3. Hydrodynamic Investigation of HIV VLP TFF
- Four Class Scheme (4CS): Each membrane type (MWCO) corresponds to one class. Four classes in total (100 kDa, 300 kDa, 500 kDa and 750 kDa). Each class contains nine measurements.
- One Class Scheme (1CS): All 36 measurements are enclosed in one single class.
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADIS | Acquired Immunodeficiency Syndrome |
AFM | Atomic Force Microscopy |
bald | Non-decorated |
DLS | Dynamic Light Scattering |
ELISA | Enzyme-Linked Immunosorbent Assay |
Env | Envelope glycoproteins |
Gag | Group-specific antigen |
HEK293F | Human Embryonic Kidney 293 |
HIV | Human Immunodeficiency Virus |
HPV | Human Papillomavirus |
MWCO | Molecular Weight Cut-Off |
PFBM | Particle Friction Based Model |
PP layer | Particle Polarization layer |
SDS-PAGE | Sodium Dodecyl Sulfate–Polyacrylamide Gel Electrophoresis |
TEM | Transmission Electron Microscopy |
TFF | Tangential Flow Filtration |
TMP | Transmembrane Pressure |
UF | Ultrafiltration |
VLP | Virus-Like Particle |
Axial spherical drag coefficient | |
Radial spherical drag coefficient | |
Hydraulic diameter | |
Particle diameter | |
Dynamic viscosity | |
Axial drag force | |
Radial drag force | |
Friction force | |
Wall shear rate | |
J | Flux |
Critical flux | |
Correction function | |
m | Slope |
Static friction coefficient | |
Kinematic viscosity | |
Reynolds number | |
Axial Reynolds number | |
Radial Reynolds number | |
Density | |
Wall shear stress | |
t | Time |
u | Velocity |
Velocity at the center of the VLP | |
Velocity permeate |
References
- Dagnaw Tegegne, K.; Cherie, N.; Tadesse, F.; Tilahun, L.; Kassaw, M.W.; Biset, G. Incidence and Predictors of Opportunistic Infections Among Adult HIV Infected Patients on Anti-Retroviral Therapy at Dessie Comprehensive Specialized Hospital, Ethiopia: A Retrospective Follow-Up Study. HIV/AIDS 2022, 14, 195–206. [Google Scholar] [CrossRef]
- Chen, C.W.; Saubi, N.; Joseph-Munné, J. Design Concepts of Virus-Like Particle-Based HIV-1 Vaccines. Front. Immunol. 2020, 11, 573157. [Google Scholar] [CrossRef] [PubMed]
- Beltran-Pavez, C.; Bontjer, I.; Gonzalez, N.; Pernas, M.; Merino-Mansilla, A.; Olvera, A.; Miro, J.M.; Brander, C.; Alcami, J.; Sanders, R.W.; et al. Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses. J. Virol. 2022, 96, e0134321. [Google Scholar] [CrossRef]
- Gonelli, C.A.; King, H.A.D.; Mackenzie, C.; Sonza, S.; Center, R.J.; Purcell, D.F.J. Immunogenicity of HIV-1-Based Virus-like Particles with Increased Incorporation and Stability of Membrane-Bound Env. Vaccines 2021, 9, 239. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Narayanan, E.; Liu, Q.; Tsybovsky, Y.; Boswell, K.; Ding, S.; Hu, Z.; Follmann, D.; Lin, Y.; Miao, H.; et al. A multiclade env-gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques. Nat. Med. 2021, 27, 2234–2245. [Google Scholar] [CrossRef]
- Van Heuvel, Y.; Schatz, S.; Rosengarten, J.F.; Stitz, J. Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine. Toxins 2022, 14, 138. [Google Scholar] [CrossRef] [PubMed]
- Cervera, L.; Gòdia, F.; Tarrés-Freixas, F.; Aguilar-Gurrieri, C.; Carrillo, J.; Blanco, J.; Gutiérrez-Granados, S. Production of HIV-1-based virus-like particles for vaccination: Achievements and limits. Appl. Microbiol. Biotechnol. 2019, 103, 7367–7384. [Google Scholar] [CrossRef]
- Gheysen, D.; Jacobs, E.; de Foresta, F.; Thiriart, C.; Francotte, M.; Thines, D.; de Wilde, M. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell 1989, 59, 103–112. [Google Scholar] [CrossRef]
- Jaffray, A.; Shephard, E.; van Harmelen, J.; Williamson, C.; Williamson, A.L.; Rybicki, E.P. Human immunodeficiency virus type 1 subtype C Gag virus-like particle boost substantially improves the immune response to a subtype C gag DNA vaccine in mice. J. Gen. Virol. 2004, 85, 409–413. [Google Scholar] [CrossRef]
- Rosengarten, J.F.; Schatz, S.; Wolf, T.; Barbe, S.; Stitz, J. Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes. Virology 2022, 568, 41–48. [Google Scholar] [CrossRef]
- Crooks, E.T.; Moore, P.L.; Franti, M.; Cayanan, C.S.; Zhu, P.; Jiang, P.; de Vries, R.P.; Wiley, C.; Zharkikh, I.; Schülke, N.; et al. 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 2007, 366, 245–262. [Google Scholar] [CrossRef] [Green Version]
- Lavado-García, J.; Jorge, I.; Boix-Besora, A.; Vázquez, J.; Gòdia, F.; Cervera, L. Characterization of HIV-1 virus-like particles and determination of Gag stoichiometry for different production platforms. Biotechnol. Bioeng. 2021, 118, 2660–2675. [Google Scholar] [CrossRef]
- Rosengarten, J.F.; Schatz, S.; Stitz, J. Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle (VLP)-Based Vaccines Using a Capture Assay. J. Vis. Exp. Jove 2022, 180. [Google Scholar] [CrossRef] [PubMed]
- van Snippenberg, W.; Gleerup, D.; Rutsaert, S.; Vandekerckhove, L.; de Spiegelaere, W.; Trypsteen, W. Triplex digital PCR assays for the quantification of intact proviral HIV-1 DNA. Methods 2022, 201, 41–48. [Google Scholar] [CrossRef]
- Wu, G.; Cheney, C.; Huang, Q.; Hazuda, D.J.; Howell, B.J.; Zuck, P. Improved Detection of HIV Gag p24 Protein Using a Combined Immunoprecipitation and Digital ELISA Method. Front. Microbiol. 2021, 12, 636703. [Google Scholar] [CrossRef] [PubMed]
- Tang, Y.W.; Ou, C.Y. Past, present and future molecular diagnosis and characterization of human immunodeficiency virus infections. Emerg. Microbes Infect. 2012, 1, e19. [Google Scholar] [CrossRef] [PubMed]
- Hengelbrock, A.; Helgers, H.; Schmidt, A.; Vetter, F.L.; Juckers, A.; Rosengarten, J.F.; Stitz, J.; Strube, J. Digital Twin for HIV-Gag VLP Production in HEK293 Cells. Processes 2022, 10, 866. [Google Scholar] [CrossRef]
- Kramberger, P.; Urbas, L.; Štrancar, A. Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages. Hum. Vaccines Immunother. 2015, 11, 1010–1021. [Google Scholar] [CrossRef]
- Chu, L.K.; Wickramasinghe, S.R.; Qian, X.; Zydney, A.L. Retention and Fouling during Nanoparticle Filtration: Implications for Membrane Purification of Biotherapeutics. Membranes 2022, 12, 299. [Google Scholar] [CrossRef]
- Helgers, H.; Hengelbrock, A.; Schmidt, A.; Rosengarten, J.; Stitz, J.; Strube, J. Process Design and Optimization towards Digital Twins for HIV-Gag VLP Production in HEK293 Cells, including Purification. Processes 2022, 10, 419. [Google Scholar] [CrossRef]
- Hengl, N.; Jin, Y.; Pignon, F.; Baup, S.; Mollard, R.; Gondrexon, N.; Magnin, A.; Michot, L.; Paineau, E. A new way to apply ultrasound in cross-flow ultrafiltration: Application to colloidal suspensions. Ultrason. Sonochemistry 2014, 21, 1018–1025. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Clark, M.M. Modeling of flux decline during crossflow ultrafiltration of colloidal suspensions. J. Membr. Sci. 1998, 149, 181–202. [Google Scholar] [CrossRef]
- Park, G.W.; Nägele, G. Modeling cross-flow ultrafiltration of permeable particle dispersions. J. Chem. Phys. 2020, 153, 204110. [Google Scholar] [CrossRef]
- Schock, G. Mikrofiltration an überströmten Membranen. Ph.D. Thesis, RWTH Aachen University, Aachen, Germany, 1985. [Google Scholar]
- Field, R.W.; Wu, J.J. Permeate Flux in Ultrafiltration Processes-Understandings and Misunderstandings. Membranes 2022, 12, 187. [Google Scholar] [CrossRef] [PubMed]
- Melin, T.; Rautenbach, R. Membranverfahren: Grundlagen der Modul- und Anlagenauslegung; mit 76 Tabellen; Springer: Berlin/Heidelberg, Germany, 2007. [Google Scholar]
- Negrete, A.; Pai, A.; Shiloach, J. Use of hollow fiber tangential flow filtration for the recovery and concentration of HIV virus-like particles produced in insect cells. J. Virol. Methods 2014, 195, 240–246. [Google Scholar] [CrossRef]
- 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. Membrane-Based Approach for the Downstream Processing of Influenza Virus-Like Particles. Biotechnol. J. 2019, 14, 1800570. [Google Scholar] [CrossRef]
- Vicente, T.; Burri, S.; Wellnitz, S.; Walsh, K.; Rothe, S.; Liderfelt, J. Fully aseptic single-use cross flow filtration system for clarification and concentration of cytomegalovirus-like particles. Eng. Life Sci. 2014, 14, 318–326. [Google Scholar] [CrossRef]
- Nguyen, T. Deckschichtbildung in Kapillarmembranen bei der Querstrom-Mikrofiltration und ihre Beeinflussung Durch Polymere Flockungsmittel. Ph.D. Thesis, Technische Universität, Dresden, Germany, 2004. [Google Scholar]
- Tam, C.K.W. The drag on a cloud of spherical particles in low Reynolds number flow. J. Fluid Mech. 1969, 38, 537–546. [Google Scholar] [CrossRef]
- Dietzel, D.; Feldmann, M.; Fuchs, H.; Schwarz, U.D.; Schirmeisen, A. Transition from static to kinetic friction of metallic nanoparticles. Appl. Phys. Lett. 2009, 95, 053104. [Google Scholar] [CrossRef]
- Ma, X.; Wang, W.; Xie, G.; Guo, D.; Wen, S. Friction measurement and motion state determination of a single polystyrene nanoparticle during manipulation. Micro Nano Lett. 2020, 15, 1140–1145. [Google Scholar] [CrossRef]
- Agmon, L.; Shahar, I.; Birodker, B.E.; Skuratovsky, S.; Jopp, J.; Berkovich, R. Application of Static Disorder Approach to Friction Force Microscopy of Catalyst Nanoparticles to Estimate Corrugation Energy Amplitudes. J. Phys. Chem. C 2019, 123, 3032–3038. [Google Scholar] [CrossRef]
- Khomenko, A.V.; Prodanov, N.V. Study of Friction of Ag and Ni Nanoparticles: An Atomistic Approach. J. Phys. Chem. C 2010, 114, 19958–19965. [Google Scholar] [CrossRef] [Green Version]
- Palacio, M.; Bhushan, B. A nanoscale friction investigation during the manipulation of nanoparticles in controlled environments. Nanotechnology 2008, 19, 315710. [Google Scholar] [CrossRef] [PubMed]
- Dietzel, D.; Feldmann, M.; Herding, C.; Schwarz, U.D.; Schirmeisen, A. Quantifying Pathways and Friction of Nanoparticles During Controlled Manipulation by Contact-Mode Atomic Force Microscopy. Tribol. Lett. 2010, 39, 273–281. [Google Scholar] [CrossRef]
- Guo, D.; Li, J.; Chang, L.; Luo, J. Measurement of the friction between single polystyrene nanospheres and silicon surface using atomic force microscopy. Langmuir ACS J. Surf. Colloids 2013, 29, 6920–6925. [Google Scholar] [CrossRef]
- Engineering ToolBox. Friction—Friction Coefficients and Calculator. 2004. Available online: https://www.engineeringtoolbox.com/friction-coefficients-d_778.html (accessed on 9 October 2022).
Parameter | Levels | ||
---|---|---|---|
TMP | 0.25 bar | 0.75 bar | 1.25 bar |
Volume flow | 9 mL/min | 13.5 mL/min | 18 mL/min |
Velocity u | 0.13 ms−1 | 0.19 ms−1 | 0.25 ms−1 |
Reynolds number | 63.42 | 95.13 | 126.84 |
Wall shear rate | 2037 s−1 | 3056 s−1 | 4074 s−1 |
Label | Substance | Refractive Index | Viscosity |
---|---|---|---|
Solvent | Water | 1.330 | 0.8872 mPa s |
Material | Protein | 1.450 | ./. |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wolf, T.; Rosengarten, J.; Härtel, I.; Stitz, J.; Barbe, S. A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration. Membranes 2022, 12, 1248. https://doi.org/10.3390/membranes12121248
Wolf T, Rosengarten J, Härtel I, Stitz J, Barbe S. A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration. Membranes. 2022; 12(12):1248. https://doi.org/10.3390/membranes12121248
Chicago/Turabian StyleWolf, Tobias, Jamila Rosengarten, Ina Härtel, Jörn Stitz, and Stéphan Barbe. 2022. "A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration" Membranes 12, no. 12: 1248. https://doi.org/10.3390/membranes12121248