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Recent Advancements and Challenges in Recombinant Expression for Commercial Production of Virus-Like Particles (VLPs)

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Bioprocess and Analytics Development for Virus-based Advanced Therapeutics and Medicinal Products (ATMPs)

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Abstract

Virus-like particles (VLPs) are mimics of native viruses that are generated from the self-assembly of viral structural proteins. The particles lack genetic material and are therefore non-infectious and safe for biomedical applications. VLPs are being considered as vaccine candidates for a number of viral infections. The threat of current and future global outbreaks of viral infections has created a strong impetus to develop platform technologies for vaccine development. The WHO has approved a number of VLP-based vaccines, e.g., Engerix® and Recombivax® against Hepatitis B virus, Cervarix® and Gardasil® against cervical cancer caused by human papillomavirus, Hecolin® for people at high risk of HEV infection, and many more are currently at different stages of clinical trials. While there is increasing interest in VLPs from the biopharma industry, the high cost and poor yield that are typically associated with VLP-based vaccines continue to be a deterrent for their commercial production. Large-scale production of VLPs requires stable and highly expressive cell lines and optimal and efficient manufacturing and purification processes, with robust monitoring and control systems in place. This review aims to highlight the role of the expression host and strategy toward successful adoption of VLPs as a therapeutic platform.

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Abbreviations

BHK:

Baby Hamster Kidney

BMMY:

Buffered Methanol-Complex Medium

CFDA:

Chinese Food and Drug Administration

CHO:

Chinese Hamster Ovary

CPV:

Canine parvovirus virus

DNA:

Deoxyribonucleic acid

ELISA:

Enzyme-linked immunosorbent assay

EMA:

European medicine agency

eVLPs:

Enveloped Virus-like particles

FDA:

Food and Drug Administration

FMDV:

Foot-and-mouth disease virus

GSK:

Glaxosmithkline

HBsAg:

Hepatitis B

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HEK293T:

Human embryonic kidney 293 cells

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

HEV:

Hepatitis E virus

HIV:

Human immunodeficiency virus

HPV:

Human papillomavirus

HuNov:

Human Norovirus

IMDM:

Iscove’s Modified Dulbecco’s Medium

JEV:

Japanese encephalitis virus

LB:

Luria–Bertani

NMPA:

National Medical Products Administration

NoV:

Noroviruses

PTM:

Post-translational modification

RNA:

Ribonucleic acid

RSV:

Respiratory syncytial virus

Sf9:

Spodoptera frugiperda cell line

SUMO:

Small Ubiquitin-like Modifier

VLPs:

Virus-like particles

WHO:

World Health Organization

YPD :

Yeast Peptone Dextrose

References

  • Alireza S, Khosrow A, Bahman AK, Alireza S-Z, Ataollah G, Manoocher M (2018) VLP production from recombinant L1/L2 HPV-16 protein expressed in Pichia pastoris. Protein Pept Lett 25:783–790

    Article  CAS  Google Scholar 

  • Alvim RGF, Itabaiana I Jr, Castilho LR (2019) Zika virus-like particles (VLPs): Stable cell lines and continuous perfusion processes as a new potential vaccine manufacturing platform. Vaccine 37:6970–6977

    Article  CAS  PubMed  Google Scholar 

  • Aw R, Spice AJ, Polizzi KM (2020) Methods for expression of recombinant proteins using a Pichia pastoris cell-free system. JCPiPS 102:e115

    CAS  Google Scholar 

  • Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10:787–796

    Article  CAS  PubMed  Google Scholar 

  • Baeshen MN, Al-He** AM, Bora RS, Ahmed MMM, Ramadan HAI, Saini KS, Baeshen NA, Redwan EM (2015) Production of biopharmaceuticals in E. coli: current scenario and future perspectives. J Microbiol Biotechnol 25:953–962

    Article  CAS  PubMed  Google Scholar 

  • Baghban R, Farajnia S, Rajabibazl M, Ghasemi Y, Mafi A, Hoseinpoor R, Rahbarnia L, Aria M (2019) Yeast expression systems: overview and recent advances. Mol Biotechnol 61:365–384

    Article  CAS  PubMed  Google Scholar 

  • Besnard L, Fabre V, Fettig M, Gousseinov E, Kawakami Y, Laroudie N, Scanlan C, Pattnaik P (2016) Clarification of vaccines: an overview of filter based technology trends and best practices. Biotechnol Adv 34:1–13

    Article  CAS  PubMed  Google Scholar 

  • Boigard H, Cimica V, Galarza JM (2018) Dengue-2 virus-like particle (VLP) based vaccine elicits the highest titers of neutralizing antibodies when produced at reduced temperature. Vaccine 36:7728–7736

    Article  CAS  PubMed  Google Scholar 

  • Boix-Besora A, Lorenzo E, Lavado-García J, Gòdia F, Cervera L (2022) Optimization, production, purification and characterization of HIV-1 GAG-based virus-like particles functionalized with SARS-CoV-2. JV 10:250

    CAS  Google Scholar 

  • Bredell H, Smith JJ, Görgens JF, van Zyl WH (2018) Expression of unique chimeric human papilloma virus type 16 (HPV-16) L1-L2 proteins in Pichia pastoris and Hansenula polymorpha. Yeast 35:519–529

    Article  CAS  PubMed  Google Scholar 

  • Brune KD, Howarth M (2018) New routes and opportunities for modular construction of particulate vaccines: stick, click, and glue. JFii 9:1432

    Google Scholar 

  • Bundy BC, Franciszkowicz MJ, Swartz JR (2008) Escherichia coli-based cell-free synthesis of virus-like particles. Biotechnol Bioeng 100:28–37

    Article  CAS  PubMed  Google Scholar 

  • Büssow K (2015) Stable mammalian producer cell lines for structural biology. Curr Opin Struct Biol 32:81–90

    Article  PubMed  Google Scholar 

  • Cervera Gracia L, Fuenmayor J, Gòdia F, Gonzalez-Domínguez I (2018) Extended gene expression for HIV-1 VLPs scale-up and production enhancement using shRNA and chemical additives. Vaccine Technology VII

    Google Scholar 

  • Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, Glenn GM, Smith GE, Frieman MB (2014) Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine 32:3169–3174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox MM, Hashimoto YJ (2011) A fast track influenza virus vaccine produced in insect cells. Joip 107:S31–S41

    CAS  Google Scholar 

  • Dai S, Wang H, Deng FJ (2018) Advances and challenges in enveloped virus-like particle (VLP)-based vaccines. JoIS 2

    Google Scholar 

  • Effio CL, Wenger L, Ötes O, Oelmeier SA, Kneusel R, Hubbuch J (2015) Downstream processing of virus-like particles: single-stage and multi-stage aqueous two-phase extraction. J Chromatogr A 1383:35–46

    Article  Google Scholar 

  • Effio CL, Baumann P, Weigel C, Vormittag P, Middelberg A, Hubbuch J (2016) High-throughput process development of an alternative platform for the production of virus-like particles in Escherichia coli. J Biotechnol 219:7–19

    Article  Google Scholar 

  • Eto Y, Saubi N, Ferrer P, Joseph-Munné J (2021) Expression of chimeric HPV-HIV protein L1P18 in Pichia pastoris; purification and characterization of the virus-like particles. JP 13:1967

    CAS  Google Scholar 

  • Farnós O, Boué O, Parra F, Martín-Alonso JM, Valdés O, Joglar M, Navea L, Naranjo P, Lleonart R (2005) High-level expression and immunogenic properties of the recombinant rabbit hemorrhagic disease virus VP60 capsid protein obtained in Pichia pastoris. J Biotechnol 117:215–224

    Article  PubMed  Google Scholar 

  • Fernández E, Toledo JR, Méndez L, González N, Parra F, Martín-Alonso JM, Limonta M, Sánchez K, Cabrales A, Estrada MP (2013) Conformational and thermal stability improvements for the large-scale production of yeast-derived rabbit hemorrhagic disease virus-like particles as multipurpose vaccine. PLoS One 8:e56417

    Article  PubMed  PubMed Central  Google Scholar 

  • Fletcher E, Krivoruchko A, Nielsen J (2016) Industrial systems biology and its impact on synthetic biology of yeast cell factories. Biotechnol Bioeng 113:1164–1170

    Article  CAS  PubMed  Google Scholar 

  • Fries L, Shinde V, Stoddard JJ, Thomas DN, Kpamegan E, Lu H, Smith G, Hickman SP, Piedra P, Glenn GM (2017) Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F) nanoparticle vaccine in older adults. Immun Ageing 14:1–14

    Article  Google Scholar 

  • Fuenmayor J, Cervera L, Rigau C, Gòdia F (2018) Enhancement of HIV-1 VLP production using gene inhibition strategies. JAm, biotechnology 102:4477–4487

    CAS  Google Scholar 

  • Garg H, Sedano M, Plata G, Punke EB, Joshi A (2017) Development of virus-like-particle vaccine and reporter assay for Zika virus. J Virol 91:e00834–e00817

    Article  PubMed  PubMed Central  Google Scholar 

  • Genzel Y (2015) Designing cell lines for viral vaccine production: where do we stand? Biotechnol J 10:728–740

    Article  CAS  PubMed  Google Scholar 

  • Glenn GM, Smith G, Fries L, Raghunandan R, Lu H, Zhou B, Thomas DN, Hickman SP, Kpamegan E, Boddapati S (2013) Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine. Vaccine 31:524–532

    Article  CAS  PubMed  Google Scholar 

  • Gregorio NE, Oza JP, Levine MZ (2019) Protocols: a user’s guide to cell-free protein synthesis. JM 2:24

    CAS  Google Scholar 

  • Grein TA, Weidner T, Czermak P (2017) Concepts for the production of viruses and viral vectors in cell culture. New insights into cell culture technology 10:62590

    Google Scholar 

  • GSK (2021) Vaccines. https://au.gsk.com/en-au/about-us/what-we-do/vaccines/

  • Gu Y, Wei M, Wang D, Li Z, **e M, Pan H, Wu T, Zhang J, Li S, **a N (2017) Characterization of an Escherichia coli-derived human papillomavirus type 16 and 18 bivalent vaccine. Vaccine 35:4637–4645

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Fordjour FK, Tsai SJ, Morrell JC, Gould SJ (2021) Choice of selectable marker affects recombinant protein expression in cells and exosomes. JJoBC 297

    Google Scholar 

  • Gupta SK, Shukla P (2016) Advanced technologies for improved expression of recombinant proteins in bacteria: perspectives and applications. Crit Rev Biotechnol 36:1089–1098

    Article  CAS  PubMed  Google Scholar 

  • Herzog C, Hartmann K, Künzi V, Kürsteiner O, Mischler R, Lazar H, Glück RJV (2009) Eleven years of Inflexal® V—a virosomal adjuvanted influenza vaccine 27:4381–4387

    CAS  PubMed  Google Scholar 

  • Hilleman MR (1987) Yeast recombinant hepatitis B vaccine. Infection 15:3–7

    Article  CAS  PubMed  Google Scholar 

  • Huang M, Wang G, Qin J, Petranovic D, Nielsen J (2018) Engineering the protein secretory pathway of Saccharomyces cerevisiae enables improved protein production. Proc Natl Acad Sci 115:E11025–E11032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huertas Romera MJ, Michán Doña CM (2019) Paving the way for the production of secretory proteins by yeast cell factories. Microb Biotechnol 1–2

    Google Scholar 

  • Josefsberg JO, Buckland B (2012) Vaccine process technology. Biotechnol Bioeng 109:1443–1460

    Article  CAS  PubMed  Google Scholar 

  • Juturu V, Wu JC (2018) Heterologous protein expression in Pichia pastoris: latest research progress and applications. ChemBioChem 19:7–21

    Article  CAS  PubMed  Google Scholar 

  • Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, Plested JS, Zhu M, Cloney-Clark S, Zhou H (2020) Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med 383:2320–2332

    Article  CAS  PubMed  Google Scholar 

  • Kim H-J, Son HS, Lee SW, Yoon Y, Hyeon J-Y, Chung GT, Lee J-W, Yoo JS (2019) Efficient expression of enterovirus 71 based on virus-like particles vaccine. JPO 14:e0210477

    Article  CAS  Google Scholar 

  • Kis Z, Shattock R, Shah N, Kontoravdi C (2019) Emerging technologies for low-cost, rapid vaccine manufacture. Biotechnol J 14:1800376

    Article  CAS  Google Scholar 

  • Lai C-C, Cheng Y-C, Chen P-W, Lin T-H, Tzeng T-T, Lu C-C, Lee M-S, Hu AY-C (2019) Process development for pandemic influenza VLP vaccine production using a baculovirus expression system. JJobe 13:1–9

    CAS  Google Scholar 

  • Lavado-García J, González-Domínguez I, Cervera L, Jorge I, Vázquez JS, Gòdia F (2020) Molecular characterization of the coproduced extracellular vesicles in HEK293 during virus-like particle production. J Proteome Res 19:4516–4532

    Article  PubMed  PubMed Central  Google Scholar 

  • Le DT, Müller KM (2021) In vitro assembly of virus-like particles and their applications. Life 11:334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le DT, Radukic MT, Müller KM (2019) Adeno-associated virus capsid protein expression in Escherichia coli and chemically defined capsid assembly. Sci Rep 9:1–10

    Article  Google Scholar 

  • Legastelois I, Buffin S, Peubez I, Mignon C, Sodoyer R, Werle B (2017) Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules. Human Vaccines Immunotherap 13:947–961

    Article  Google Scholar 

  • Li SW, Zhang J, Li YM, Ou SH, Huang GY, He ZQ, Sheng XG, **an YL, Pang SQ, Ng MH (2005) A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine 23:2893–2901

    Article  CAS  PubMed  Google Scholar 

  • Li C, Liu F, Liang M, Zhang Q, Wang X, Wang T, Li J, Li D (2010) Hantavirus-like particles generated in CHO cells induce specific immune responses in C57BL/6 mice. Vaccine 28(26):4294–4300

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Wang B, Wang F, Yang Z, Gao D, Zhang C, Ma L, Yu X (2019) Soluble expression of single-chain variable fragment (scFv) in Escherichia coli using superfolder green fluorescent protein as fusion partner. Appl Microbiol Biotechnol 103:6071–6079

    Article  CAS  PubMed  Google Scholar 

  • Looser V, Bruhlmann B, Bumbak F, Stenger C, Costa M, Camattari A, Fotiadis D, Kovar K (2015) Cultivation strategies to enhance productivity of Pichia pastoris: a review. Biotechnol Adv 33:1177–1193

    Article  CAS  PubMed  Google Scholar 

  • Mariz FC, Coimbra EC, Jesus ALS, Nascimento LM, Torres FAG, Freitas AC (2015) Development of an IP-Free biotechnology platform for constitutive production of HPV16 L1 capsid protein using the Pichia pastoris PGK1 promoter. Biomed Res Int 2015

    Google Scholar 

  • Merlin M, Gecchele E, Capaldi S, Pezzotti M, Avesani L (2014) Comparative evaluation of recombinant protein production in different biofactories: the green perspective. Biomed Res Int 2014

    Google Scholar 

  • Mittal M, Banerjee M, Lua LH, Rathore AS (2021) Current status and future challenges in transitioning to continuous bioprocessing of virus-like particles. JJoCT, Biotechnology

    Google Scholar 

  • Nishida T, Kubota S, Takigawa M (2017) Production of recombinant CCN2 protein by mammalian cells. In: CCN Proteins. Springer, pp 95–105

    Chapter  Google Scholar 

  • Owczarek B, Gerszberg A, Hnatuszko-Konka K (2019) A brief reminder of systems of production and chromatography-based recovery of recombinant protein biopharmaceuticals. Biomed Res Int

    Google Scholar 

  • Pattenden LK, Middelberg APJ, Niebert M, Lipin DI (2005) Towards the preparative and large-scale precision manufacture of virus-like particles. Trends Biotechnol 23:523–529

    Article  CAS  PubMed  Google Scholar 

  • Peacey M, Wilson S, Baird MA, Ward VK (2007) Versatile RHDV virus-like particles: Incorporation of antigens by genetic modification and chemical conjugation. Biotechnol Bioeng 98:968–977

    Article  CAS  PubMed  Google Scholar 

  • Peixoto C, Sousa MFQ, Silva AC, Carrondo MJT, Alves PM (2007) Downstream processing of triple layered rotavirus like particles. J Biotechnol 127(3):452–461

    Article  CAS  PubMed  Google Scholar 

  • Portnoff AD, Patel N, Massare MJ, Zhou H, Tian J-H, Zhou B, Shinde V, Glenn GM, Smith G (2020) Influenza hemagglutinin nanoparticle vaccine elicits broadly neutralizing antibodies against structurally distinct domains of H3N2 HA. Vaccine 8:99

    Article  CAS  Google Scholar 

  • Possee RD, Chambers AC, Graves LP, Aksular M, King LA (2019) Recent developments in the use of baculovirus expression vectors. JCIiMB 34:215–230

    Google Scholar 

  • Potvin G, Ahmad A, Zhang Z (2012) Bioprocess engineering aspects of heterologous protein production in Pichia pastoris: a review. Biochem Eng J 64:91–105

    Article  CAS  Google Scholar 

  • Qian C, Liu X, Xu Q, Wang Z, Chen J, Li T, Zheng Q, Yu H, Gu Y, Li S (2020) Recent progress on the versatility of virus-like particles. Vaccine 8:139

    Article  CAS  Google Scholar 

  • Qiao Y-L, Wu T, Li R-C, Hu Y-M, Wei L-H, Li C-G, Chen W, Huang S-J, Zhao F-H, Li M-Q (2020) Efficacy, safety, and immunogenicity of an Escherichia coli-produced bivalent human papillomavirus vaccine: an interim analysis of a randomized clinical trial. J Natl Cancer Inst 112:145–153

    Article  PubMed  Google Scholar 

  • Rey FA, Lok S-M (2018) Common features of enveloped viruses and implications for immunogen design for next-generation vaccines. JC 172:1319–1334

    CAS  Google Scholar 

  • Roldão A, Mellado MCM, Castilho LR, Carrondo MJT, Alves PM (2010) Virus-like particles in vaccine development. Expert Rev Vaccines 9:1149–1176

    Article  PubMed  Google Scholar 

  • Rosano GL, Ceccarelli EA (2014) Recombinant protein expression in Escherichia coli: advances and challenges. Front Microbiol 5:172

    Article  PubMed  PubMed Central  Google Scholar 

  • Saraswat S, Athmaram TN, Parida M, Agarwal A, Saha A, Dash PK (2016) Expression and characterization of yeast derived chikungunya virus like particles (CHIK-VLPs) and its evaluation as a potential vaccine candidate. PLoS Negl Trop Dis 10:e0004782

    Article  PubMed  PubMed Central  Google Scholar 

  • Schellenbacher C, Roden RBS, Kirnbauer R (2017) Developments in L2-based human papillomavirus (HPV) vaccines. Virus Res 231:166–175

    Article  CAS  PubMed  Google Scholar 

  • Sequeira DP, Correia R, Carrondo MJT, Roldão A, Teixeira AP, Alves PM (2018) Combining stable insect cell lines with baculovirus-mediated expression for multi-HA influenza VLP production. Vaccine 36:3112–3123

    Article  CAS  PubMed  Google Scholar 

  • Sheng J, Lei S, Yuan L, Feng X (2017) Cell-free protein synthesis of norovirus virus-like particles. RSC Adv 7:28837–28840

    Article  CAS  Google Scholar 

  • Shrivastava A, Joshi S, Guttman A, Rathore AS (2022) N-Glycosylation of monoclonal antibody therapeutics: a comprehensive review on significance and characterization. JACA 339828

    Google Scholar 

  • Slifka MK, Amanna IJ (2019) Role of multivalency and antigenic threshold in generating protective antibody responses. Front Immunol 10:956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith G, Liu Y, Flyer D, Massare MJ, Zhou B, Patel N, Ellingsworth L, Lewis M, Cummings JF, Glenn G (2017) Novel hemagglutinin nanoparticle influenza vaccine with Matrix-M™ adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted A (H3N2) subtypes. Vaccine 35:5366–5372

    Article  CAS  PubMed  Google Scholar 

  • Spice AJ, Aw R, Bracewell DG, Polizzi KM (2020) Biotechnology: synthesis and assembly of hepatitis B virus-like particles in a Pichia pastoris cell-free system. JFiB 8:72

    Google Scholar 

  • Stepanenko AA, Dmitrenko VV (2015) HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. Gene 569:182–190

    Article  CAS  PubMed  Google Scholar 

  • Strobl F, Ghorbanpour SM, Palmberger D, Striedner G (2020) Evaluation of screening platforms for virus-like particle production with the baculovirus expression vector system in insect cells. JSr 10:1–9

    Google Scholar 

  • Thompson CM, Petiot E, Mullick A, Aucoin MG, Henry O, Kamen AA (2015) Critical assessment of influenza VLP production in Sf9 and HEK293 expression systems. BMC Biotechnol 15:1–12

    Article  Google Scholar 

  • Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, De Jongh WA, Clemmensen S, Roeffen W, van de Vegte-Bolmer M, Van Gemert GJ (2016) Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J Nanobiotechnol 14:1–16

    Article  Google Scholar 

  • Tian J-H, Patel N, Haupt R, Zhou H, Weston S, Hammond H, Logue J, Pornoff A, Norton J, Guebre-Xabier M (2020) M SARSCoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. Nat Commun

    Google Scholar 

  • Tomé-Amat J, Fleischer L, Parker SA, Bardliving CL, Batt CA (2014) Secreted production of assembled Norovirus virus-like particles from Pichia pastoris. Microb Cell Factories 13:134

    Article  Google Scholar 

  • Trial UC (2021) U.S. Clinical Trials. Safety study of recombinant M2e influenza – a vaccine in healthy adults (FLU-A). http://www.clinicaltrials.gov/ct2/show/NCT00819013?term=sanofi+and+influenza+and+m2e&rank=1. Accessed 12 Apr 2012

  • Urakami A, Sakurai A, Ishikawa M, Yap ML, Flores-Garcia Y, Haseda Y, Aoshi T, Zavala FP, Rossmann MG, Kuno S (2017) Development of a novel virus-like particle vaccine platform that mimics the immature form of alphavirus. Clin Vaccine Immunol 24:e00090–e00017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vicente T, Roldão A, Peixoto C, Carrondo MJT, Alves PM (2011) Large-scale production and purification of VLP-based vaccines. J Invertebr Pathol 107:S42–S48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vieira Gomes AM, Souza Carmo T, Silva Carvalho L, Mendonça Bahia F, Parachin NS (2018) Comparison of yeasts as hosts for recombinant protein production. Microorganisms 6:38

    Article  PubMed  PubMed Central  Google Scholar 

  • Wagner JM, Pajerowski JD, Daniels CL, McHugh PM, Flynn JA, Balliet JW, Casimiro DR, Subramanian S (2014) Enhanced production of Chikungunya virus-like particles using a high-pH adapted spodoptera frugiperda insect cell line. PLoS One 9(4):e94401

    Article  PubMed  PubMed Central  Google Scholar 

  • Wei M, Wang D, Li Z, Song S, Kong X, Mo X, Yang Y, He M, Li Z, Huang B (2018) N-terminal truncations on L1 proteins of human papillomaviruses promote their soluble expression in Escherichia coli and self-assembly in vitro. Emerg Microb Infect 7:1–12

    Google Scholar 

  • Welsch S, Müller B, Kräusslich H-G (2007) More than one door–budding of enveloped viruses through cellular membranes. FEBS Lett 581:2089–2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Werten MWT, Eggink G, Stuart MAC, de Wolf FA (2019) Production of protein-based polymers in Pichia pastoris. Biotechnol Adv 37:642–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • WHO (2014) Guidelines on the quality, safety and efficacy ofrecombinant malaria vaccines targeting the pre-erythrocytic and blood stagesof Plasmodium falciparum. World Health Organization

    Google Scholar 

  • **ao Y, Chen H-Y, Wang Y, Yin B, Lv C, Mo X, Yan H, Xuan Y, Huang Y, Pang W (2016) Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle. BMC Biotechnol 16:1–9

    Article  Google Scholar 

  • Xu J, Guo H-C, Wei Y-Q, Dong H, Han S-C, Ao D, Sun D-H, Wang H-M, Cao S-Z, Sun S-Q (2014) Self-assembly of virus-like particles of canine parvovirus capsid protein expressed from Escherichia coli and application as virus-like particle vaccine. Appl Microbiol Biotechnol 98:3529–3538

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Zhang Z (2018) Engineering strategies for enhanced production of protein and bio-products in Pichia pastoris: a review. Biotechnol Adv 36:182–195

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Gao F, Wang X, Shi L, Zhou Z, Jiang Y, Ma X, Zhang C, Zhou C, Zeng X (2020) Development and characterization of an enterovirus 71 (EV71) virus-like particles (VLPs) vaccine produced in Pichia pastoris. Human Vaccines Immunotherap 16:1602–1610

    Article  CAS  Google Scholar 

  • Yazdani R, Shams-Bakhsh M, Hassani-Mehraban A, Arab SS, Thelen N, Thiry M, Crommen J, Fillet M, Jacobs N, Brans A (2019) Production and characterization of virus-like particles of grapevine fanleaf virus presenting L2 epitope of human papillomavirus minor capsid protein. JBb 19:1–12

    Google Scholar 

  • Zeltins A (2013) Construction and characterization of virus-like particles: a review. Mol Biotechnol 53:92–107

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Wei M, Pan H, Lin Z, Wang K, Weng Z, Zhu Y, **n L, Zhang J, Li S (2014) Robust manufacturing and comprehensive characterization of recombinant hepatitis E virus-like particles in Hecolin®. Vaccine 32:4039–4050

    Article  CAS  PubMed  Google Scholar 

  • Zheng M, Jiang J, Zhang X, Wang N, Wang K, Li Q, Li T, Lin Q, Wang Y, Yu H (2018) Characterization of capsid protein (p495) of hepatitis E virus expressed in Escherichia coli and assembling into particles in vitro. Vaccine 36:2104–2111

    Article  CAS  PubMed  Google Scholar 

  • Zhu F-C, Zhang J, Zhang X-F, Zhou C, Wang Z-Z, Huang S-J, Wang H, Yang C-L, Jiang H-M, Cai J-P (2010) Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 376:895–902

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Authors would like to acknowledge funding support from the Council of Scientific and Industrial Research (CSIR) and the University Grants Commission (UGC), Human Resource Development Group (UGC-Ref. No.: 598/CSIR-UGC NET DEC.2017).

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Author notes

  1. Abhilasha K. Rani and Wajihul Hasan Khan contributed equally with all other contributors.

Authors and Affiliations

  1. School of Interdisciplinary Research, Indian Institute of Technology, New Delhi, India

    Abhilasha K. Rani, Manidipa Banerjee & Anurag S. Rathore

  2. Department of Chemical Engineering, Indian Institute of Technology, New Delhi, India

    Wajihul Hasan Khan & Anurag S. Rathore

  3. Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India

    Manidipa Banerjee

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  1. Abhilasha K. Rani
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  2. Wajihul Hasan Khan
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  3. Manidipa Banerjee
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  4. Anurag S. Rathore
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Corresponding author

Correspondence to Anurag S. Rathore .

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Editors and Affiliations

  1. Boehringer Ingelheim International GmbH/ ViraTherapeutics GmbH, Innsbruck, Austria

    Saurabh Gautam

  2. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany

    Abhilash I. Chiramel

  3. F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Roland Pach

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Rani, A.K., Khan, W.H., Banerjee, M., Rathore, A.S. (2023). Recent Advancements and Challenges in Recombinant Expression for Commercial Production of Virus-Like Particles (VLPs). In: Gautam, S., Chiramel, A.I., Pach, R. (eds) Bioprocess and Analytics Development for Virus-based Advanced Therapeutics and Medicinal Products (ATMPs). Springer, Cham. https://doi.org/10.1007/978-3-031-28489-2_17

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