Heterologous Production of Human Papillomavirus L1 Capsid Protein: Systematic Review and Meta-analysis

Authors

  • Andre Hendrawan School of Life Sciences and Technology, Institut Teknologi Bandung https://orcid.org/0000-0002-5495-7620
  • Azzania Fibriani School of Life Sciences and Technology, Institut Teknologi Bandung

DOI:

https://doi.org/10.5614/3bio.2022.4.1.5

Keywords:

HPV, L1, L1 production rate, anti-L1 IgG titer, Pearson?s correlation analysis

Abstract

The coverage of HPV vaccination in Indonesia remains low due to the high-cost vaccination. The vaccine prices were affected by the production rate of L1, the active substance of HPV vaccines. L1 has been produced using various organisms with varying L1 production rates and immunogenicity. A systematic review and meta-analysis were conducted to determine the organism producing L1 with the highest production, treatments affecting the L1 expression rate, and immunogenicity (represented by anti-L1 IgG titer in mice). The data of L1 titer, induction period, and IgG titer were extracted from 19 articles that have passed the articles screening. The L1 titer and induction period data were used to calculate the L1 production rate, while the IgG titer was used in the immunogenicity analysis. On a 95% confidence level, the meta-analysis revealed weak evidence that E. coli produced L1 at the highest rate. The highest IgG titer was induced using L1 expressed in Saccharomyces cerevisiae, albeit insufficient evidence on 95% confidence level. Pearson?s correlation analysis showed that the concentration of glucose, IPTG, NH4+, K+, Ca2+, Mn2+, Fe2+, Zn2+, B4O72?, H2PO4?, HPO42?, Mo7O246?, and citric acid had a positive correlation with L1 production rate in E. coli. The treatment injection doses positively correlated with IgG titer in S. cerevisiae. This study reveals the mineral salts as the potential treatments to increase L1 production rates.

References

Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piros M, Znaor A, Soerjomataram I, Bray F. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today [cited 2021 Dec 1]

Johansson C, Schwartz S. Regulation of human papillomavirus gene expression by splicing and polyadenylation. Nature Reviews Microbiology. 2013 Mar; 11(4): 239-251. DOI: https://doi.org/10.1038/nrmicro2984

Muz N, Bosch FX, de SanjosS, Herrero R, CastellsaguX, Shah KV, Snijders PJF, Meijer CJLM. Epidemiologic classification of human papillomavirus types associated with cervical cancer. New England Journal of Medicines. 2003 Feb;348(6): 518-527. DOI: https://doi.org/10.1056/NEJMoa021641

Ayuningtyas D, Sutrisnawati NND. Indonesia?s readiness to implement the HPV vaccine mandatory for school age. Health Science Journal of Indonesia. 2018 Dec; 9(2): 107-118. DOI: https://doi.org/10.22435/hsji.v9i2.910

Schiller JT, Lowy DR. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nature Reviews Microbiology. 2012 Oct; 10(10): 681-692. DOI: https://doi.org/10.1038/nrmicro2872

Bang HB, Lee YH, Lee YJ, Jeong, KJ. High-level production of human papillomavirus (HPV) type 16 L1 in Escherichia coli. Journal of Microbiology and Biotechnology. 2016 Feb;26(2): 356-363. DOI: https://doi.org/10.4014/jmb.1511.11010

Kim HJ, Cho SY, Park M, Kim H. Comparison of the size distributions and immunogenicity of human papillomavirus type 16 L1 virus-like particles produced in insect and yeast cells. Archives of Pharmacal Research. 2018 Apr; 41(5): 544-553. DOI: https://doi.org/10.1007/s12272-018-1024-4

Rao NH, Babu PB, Rajendra L, Sriraman R, Pang YS, Schiller JT, Srinivasan VA. Expression of codon optimized major capsid protein (L1) of human papillomavirus type 16 and 18 in Pichia pastoris; purification and characterization of the virus-like particles. Vaccine. 2011 Jul;29(43): 7326-7334. DOI: https://doi.org/10.1016/j.vaccine.2011.07.071

Zanotto C, Pozzi E, Pacchioni S, Bissa M, Morghen CDG, Radaelli A. Construction and characterisation of a recombinant fowlpox virus that expresses the human papilloma virus L1 protein. Journal of Translational Medicine. 2011 Nov;9(190). DOI: https://doi.org/10.1111/j.1745-7270.2008.00417.x

Regnard GL, Halley-Stott RP, Tanzer FL, Hitzeroth II, Rybicki EP. High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector. Plant Biotechnology Journal. 2009 Nov;8(1): 38-46. DOI: https://doi.org/10.1111/j.1467-7652.2009.00462.x

Bredell H, Smith JJ, Ggens JF, van Zyl WH. Expression of unique chimeric human papilloma virus type 16 (HPV-16) L1-L2 proteins in Pichia pastoris and Hansenula polymorpha. Yeast. 2018 Apr;35(9): 519-529. DOI: https://doi.org/10.1002/yea.3318

Kim HJ, Jin Y, Kim HJ. The concentration of carbon source in the medium affects the quality of virus-like particles of human papillomavirus type 16 produced in Saccharomyces cerevisiae. PLoS ONE. 2014 Apr;9(4): 1-7. DOI: https://doi.org/10.1371/journal.pone.0094467

Global Alliances for Vaccines and Immunisation. Key concepts: economics of vaccine production. Available from: https://www.who.int/immunization/programmes_systems/financing/analyses/en/briefcase_vacproduction.pdf [Cited 2022 March 9]

Pan D, Zha X, Yu X, Wu Y. Enhanced expression of soluble human papillomavirus L1 through co-expression of molecular chaperonin in Escherichia coli. Protein Expression and Purification. 2015 Dec;120: 92-98. DOI: https://doi.org/10.1016/j.pep.2015.12.016

Chen Y, Liu Y, Zhang G, Wang A, Dong Z, Qi Y, Wang J, Zhao B, Li N, Jiang M. Human papillomavirus L1 protein expressed in Escherichia coli self-assembles into virus-like particles that are highly immunogenic. Virus Research. 2016 Apr;220: 97-103. DOI: https://doi.org/10.1016/j.virusres.2016.04.017

Kelsall SR, Kulski JK. Expression of the major capsid protein of human papillomavirus type 16 in Escherichia coli. Journal of Virological Methods. 1995 May;53(1): 75-90. DOI: https://doi.org/10.1016/0166-0934(95)00004-e

Park M, Kim HJ, Kim H. Optimum conditions for production and purification of human papillomavirus type 16 L1 protein from Saccharomyces cerevisiae. Protein Expression and Purification. 2008 Feb;59(1): 175-181. DOI: https://doi.org/10.1016/j.pep.2008.01.021

Kim HJ, Kwag H, Jin Y, Kim H. The composition of the carbon source and the time of cell harvest are critical determinants of the final yield of human papillomavirus type 16 L1 protein produced in Saccharomyces cerevisiae. Protein Expression and Purification. 2011 Jun;80(1): 52-60. DOI: https://doi.org/10.1016/j.pep.2011.06.010

Kim HJ, Kwag H, Kim H. Codon optimization of the human papillomavirus type 58 L1 gene enhances the expression of soluble L1 protein in Saccharomyces cerevisiae. Biotechnology Letters. 2012 Nov;35(3): 413-421. DOI: https://doi.org/10.1007/s10529-012-1097-y

Bazan SB, Chaves AAM, Aires KA, Cianciarullo AM, Garcea RL, Ho PL. Expression and characterization of HPV-16 L1 capsid protein in Pichia pastoris. Archives of Virology. 2009 Sep;154(10): 1609-1617. DOI: https://doi.org/10.1007/s00705-009-0484-8

Kirnbauer R, Taub J, Greenstone H, Roden R, Dst M, Gissman L, Lowy DR, Schiller JT. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. Journal of Virology. 1993 Dec;67(12): 6929-6936. DOI: https://doi.org/10.1128/JVI.67.12.6929-6936.1993

Wang M, Wang L, Chen L, Han Y, Zou Y, Si J, Song G. Expression of human papillomavirus type 6 L1 and L2 isolated in China and self assembly of virus-like particles by the products. Acta Biochimica et Biophysica Sinica. 2003 Jan;35(1): 27-34

Zheng J, Ma J, Yang X, Liu H, Cheng H, Si L, Wang Y. Highly efficient and economical baculovirus expression system for preparing human papillomavirus type16 virus-like particle. Acta Biochimica et Biophysica Sinica. 2004 Aug;36(8): 548-552. DOI: https://doi.org/10.1093/abbs/36.8.548

Baek J, Seo J, Kim I, Kim CH. Production and purification of human papillomavirus type 33 L1 virus-like particles from Spodoptera frugiperda 9 cells using two-step column chromatography. Protein Expression and Purification. 2010 Aug;75(2): 211-217. DOI: https://doi.org/10.1016/j.pep.2010.08.005

Sun B, Zhao D, Zhang X, Gu T, Yu X, Sun S, Zhao X, Wei L, Liu D, Yan H, Meng X, Kong W, Xu F, Yang P, Jiang C. Development a scalable production process for truncated human papillomavirus type-6 L1 protein using WAVE Bioreactor and hollow fiber membrane. Applied Microbiology and Biotechnology. 2015 Oct;100(3): 1231-1240. Available from: DOI: https://doi.org/10.1007/s00253-015-6974-6

Zheng J, Yang X, Sun Y, Lai B, Wang Y. Stable high-level expression of truncated human papillomavirus type 16 L1 protein in Drosophila Schneider-2 cells. Acta Biochimica et Biophysica Sinica. 2008 May;40(5): 437-442. DOI: https://doi.org/10.1111/j.1745-7270.2008.00417.x

Yu XC, Margolin W. Ca2+-mediated GTP-dependent dynamic assembly of bacterial cell division protein FtsZ into asters and polymer networks in vitro. EMBO Journal. 1997 Sep;16(17): 5455-5463. DOI: https://doi.org/10.1093/emboj/16.17.5455

Margolin W. FtsZ and the division of prokaryotic cells and organelles. Nature Reviews Molecular Cell Biology. 2005 Nov;6(11): 862-871. DOI: https://doi.org/10.1038/nrm1745

Kusakabe T, Richardson CC. The role of zinc motif in sequence recognition by DNA primases. Journal of Biological Chemistry. 1996 Aug;271(32): 19563-19570. DOI: https://doi.org/10.1074/jbc.271.32.19563

Chen XS, Casini G, Harrison SC, Garcea RL. Papillomavirus capsid protein expression in Escherichia coli: purification and assembly of HPV11 and HPV16 L1. Journal of Molecular Biology. 2001 Mar;307(1): 173-182. DOI: https://doi.org/10.1006/jmbi.2000.4464

Zohar BA, Kolodkin-Gal I. Quorum sensing in Escherichia coli: interkingdom, inter- and intraspecies dialogues, and a suicide-inducing peptide. In: Kalia VC. (eds.) Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight. New Delhi, India: Springer India; 2007. p. 85-99

Madigan MT. Bender KS, Buckley DH, Sattley WM, Stahl DA. Brock Biology of Microorganisms. 15th ed., Pearson, 2019

Lundberg JO, Weitzberg E, Cole JA, Benjamin N. Nitrate, bacteria and human health. Nature Reviews Microbiology. 2004 Jul;2(8): 593-602. DOI: https://doi.org/10.1038/nrmicro929

Kornfeld R, Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annual Review of Biochemistry. 1985;54: 631-634

Wildt S, Gerngross TU. The humanization of N-glycosylation pathways in yeast. Nature Reviews Microbiology. 2005 Feb;3(2): 119-128

Conde R, Cueva R, Pablo G, Polaina J, Larriba G. A search for hyperglycosylation signals in yeast glycoproteins. Journal of Biological Chemistry. 2004 Oct;279(42): 43789-43798

Wolfert MA, Boons G. Adaptive immune activation: glycosylation does matter. Nature Chemical Biology. 2013 Dec;9: 776-784

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Published

2022-04-20

Issue

Vol. 4 No. 1 (2022)

Section

Review Article

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Copyright (c) 2022 Andre Hendrawan, Azzania Fibriani

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