Research Progress of Virus-like Particles Vaccine

doi:10.19586/j.2095-2341.2024.0069

Current Biotechnology ›› 2024, Vol. 14 ›› Issue (5): 776-784.DOI: 10.19586/j.2095-2341.2024.0069

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Research Progress of Virus-like Particles Vaccine

Weili ZHAO(), Na LYU, Huiqiang LI, Yahui HE, Lulu LI, Mingli LIANG, Yanyi LI()

North China Pharmaceutical Jintan Biotechnology Co. ，Ltd. ，Shijiazhuang 050035，China

Received:2024-04-01 Accepted:2024-06-03 Online:2024-09-25 Published:2024-10-22
Contact: Yanyi LI

病毒样颗粒疫苗研究进展

赵尉吏(), 吕娜, 李会强, 何亚辉, 李露露, 梁明丽, 李岩异()

华北制药金坦生物技术股份有限公司，石家庄 050035

通讯作者: 李岩异
作者简介:赵尉吏 E-mail:18003218172@163.com；

Abstract

Abstract:

Virus-like particles （VLPs） are hollow particles containing one or more structural proteins of a certain virus. Structurally similar to intact viruses， they possess immunogenicity similar to that of intact viruses and could induce immune responses by activating antigen-presenting cells. Due to the absence of viral genomes， VLPs can be developed into safer and more cost-effective vaccine candidates. This article systematically elaborated on the classification， characterization， advantages， and expression systems of VLPs， reviewed the development history of VLP vaccines， and summarized the varieties of vaccines that have been approved for market use. At the same time， it introduced some preventive or therapeutic VLP vaccines that were currently under research and development， and explored new development strategies， further broadening the field of VLP vaccine research and development， and providing broader prospects for future research and application.

Key words: virus-like particles, VLP vaccines, characterization tools, expression system

摘要：

病毒样颗粒(virus-like particles,VLPs) 是含有某种病毒一个或多个结构蛋白的空心颗粒形态, 结构上类似完整病毒，具有与完整病毒相似的免疫原性并通过激活抗原提呈细胞诱导免疫应答，由于不含有完整的病毒基因组，因此适合用于开发更安全、成本更低的候选疫苗。系统阐述了VLPs的分类、表征、优势及表达系统，回顾了VLPs疫苗的发展历程，并汇总了已上市的疫苗品种。同时，介绍了部分在研的预防性或治疗性VLPs疫苗，并探讨了新的开发策略，进一步拓宽了VLPs疫苗的研发领域，为未来的研究与应用提供了更广阔的前景。

关键词: 病毒样颗粒, VLPs 疫苗, 表征工具, 表达系统

CLC Number:

Q939.47

Weili ZHAO, Na LYU, Huiqiang LI, Yahui HE, Lulu LI, Mingli LIANG, Yanyi LI. Research Progress of Virus-like Particles Vaccine[J]. Current Biotechnology, 2024, 14(5): 776-784.

赵尉吏, 吕娜, 李会强, 何亚辉, 李露露, 梁明丽, 李岩异. 病毒样颗粒疫苗研究进展[J]. 生物技术进展, 2024, 14(5): 776-784.

Figures/Tables 2

References 57

1	KUSHNIR N, STREATFIELD S J, YUSIBOV V. Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development[J]. Vaccine, 2012, 31(1): 58-83.
2	KLEID D G, YANSURA D, SMALL B, et al.. Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine[J]. Science, 1981, 214(4525): 1125-1129.
3	LMICHEL M, TIOLLAIS P. Hepatitis B vaccines: protective efficacy and therapeutic potential[J]. Pathol. Biol. (Paris), 2010, 58(4): 288-295.
4	LINDA H, LUA L, FRANK S, et al.. Bioengineering virus-like particles as vaccines[J].Biotechnol. Bioengin., 2014, doi:10.1002/bit.25159[2024-08-02]. .
5	WHITACRE D C, LEE B O, MILICH D R. Use of hepadnavirus core proteins as vaccine platforms[J]. Expert Rev. Vaccines, 2009, 8(11): 1565-1573.
6	SAUNDERS K, SAINSBURY F, LOMONOSSOFF G P. Efficient generation of cowpea mosaic virus empty virus-like particles by the proteolytic processing of precursors in insect cells and plants[J]. Virology, 2009, 393(2): 329-337.
7	KIRNBAUER R, TAUB J, GREENSTONE H, et al.. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles[J]. Int. J. Mol. Sci., 1993, 67(12): 6929-6936.
8	PORTA C, KOTECHA A, BURMAN A, et al.. Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen[J/OL]. PLoS Pathog., 2013, 9(3): e1003255[2024-08-02]. .
9	HEWAT E A, BOOTH T F, ROY P. Structure of correctly self-assembled bluetongue virus-like particles[J]. J. Struct. Biol., 1994, 112(3): 183-191.
10	CONNER M E, ZARLEY C D, HU B, et al.. Virus-like particles as a rotavirus subunit vaccine[J]. J. Interv. Cardiol., 1996, 174(): S88-S92.
11	KANG S M, KIM M C, COMPANS R W. Virus-like particles as universal influenza vaccines[J]. Expert Rev. Vaccines, 2012, 11(8): 995-1007.
12	FREIVALDS J, DISLERS A, OSE V, et al.. Highly efficient production of phosphorylated hepatitis B core particles in yeast Pichia pastoris [J]. Protein Expr. Purif., 2011, 75(2): 218-224.
13	KALNCIEMA I, SKRASTINA D, OSE V, et al.. Potato virus Y-like particles as a new carrier for the presentation of foreign protein stretches[J]. Mol. Biotechnol., 2012, 52(2): 129-139.
14	IBAÑEZ L I, ROOSE K, DE FILETTE M, et al.. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A[J/OL]. PLoS One, 2013, 8(3): e59081[2024-08-02]. .
15	SAINSBURY F, SAUNDERS K, ALJABALI A A A, et al.. Peptide-controlled access to the interior surface of empty virus nanoparticles[J]. ChemBioChem, 2011, 12(16): 2435-2440.
16	KUZNETSOV Y G, MCPHERSON A. Atomic force microscopy in imaging of viruses and virus-infected cells[J]. Microbiol. Mol. Biol. Rev., 2011, 75(2): 268-285.
17	ZHAO Q, ALLEN M J, WANG Y, et al.. Disassembly and reassembly improves morphology and thermal stability of human papillomavirus type 16 virus-like particles[J]. Nanomedicine, 2012, 8(7): 1182-1189.
18	EMILHIET P, DOSSET P, GODEFROY C, et al.. Nanoscale topography of hepatitis B antigen particles by atomic force microscopy[J]. Biochimie, 2011, 93(2): 254-259.
19	PEASE L F, LIPIN D I, TSAI D H, et al.. Quantitative characterization of virus-like particles by asymmetrical flow field flow fractionation, electrospray differential mobility analysis, and transmission electron microscopy[J]. Biotechnol. Bioeng., 2009, 102(3): 845-855.
20	DESCHUYTENEER M, ELOUAHABI A, PLAINCHAMP D, et al.. Molecular and structural characterization of the L1 virus-like particles that are used as vaccine antigens in Cervarix™, the AS04-adjuvanted HPV-16 and-18 cervical cancer vaccine[J]. Hum. Vaccin., 2010, 6(5): 407-419.
21	SHAH K, CHAUBEY P, MISRA N. Bioinformatics approach for screening and modeling of putative T cell epitopes from Por B protein of Neisseria meningitides as vaccine constructs[J]. Indian J. Biotechnol., 2010, 9(4):351-359.
22	MOHSEN M O, GOMES A C, CABRAL-MIRANDA G, et al.. Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination[J]. J. Control. Release, 2017, 251: 92-100.
23	NOAD R, ROY P. Virus-like particles as immunogens[J]. Trends Microbiol., 2003, 11(9): 438-444.
24	BACHMANN M F, JENNINGS G T. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns[J]. Nat. Rev. Immunol., 2010, 10(11): 787-796.
25	MOHSEN M O, ZHA L, CABRAL-MIRANDA G, et al.. Major findings and recent advances in virus-like particle (VLP)-based vaccines[J]. Semin. Immunol., 2017, 34: 123-132.
26	FRIETZE K M, PEABODY D S, CHACKERIAN B. Engineering virus-like particles as vaccine platforms[J]. Curr. Opin. Virol., 2016, 18: 44-49.
27	FIEDLER J D, HIGGINSON C, HOVLID M L, et al.. Engineered mutations change the structure and stability of a virus-like particle[J]. Biomacromolecules, 2012, 13(8): 2339-2348.
28	MOHSEN M O, BALKE I, ZINKHAN S, et al.. A scalable and highly immunogenic virus-like particle-based vaccine against SARS-CoV-2[J]. Allergy, 2022, 77(1): 243-257.
29	SASAGAWA T, PUSHKO P, STEERS G, et al.. Synthesis and assembly of virus-like particles of human papillomaviruses type 6 and type 16 in fission yeast Schizosaccharomyces pombe [J]. Virology, 1995, 206(1): 126-135.
30	LUCKOW V A, LEE S C, BARRY G F, et al.. Efficient generation of infectious recombinant baculoviruses by site-specific transposon-mediated insertion of foreign genes into a baculovirus genome propagated in Escherichia coli [J]. J. Virol., 1993, 67(8): 4566-4579.
31	ESTES M L, EWING-WILSON D, CHOU S M, et al.. Chloroquine neuromyotoxicity. clinical and pathologic perspective[J]. Am. J. Med., 1987, 82(3): 447-455.
32	BETENBAUGH M, YU M, KUEHL K, et al.. Nucleocapsid- and virus-like particles assemble in cells infected with recombinant baculoviruses or vaccinia viruses expressing the M and the S segments of Hantaan virus[J]. Virus Res., 1995, 38(2-3): 111-124.
33	ROLDÃO A, MELLADO M C M, CASTILHO L R, et al.. Virus-like particles in vaccine development[J]. Expert Rev. Vaccines, 2010, 9(10): 1149-1176.
34	GURRAMKONDA C, ADNAN A, GÄBEL T, et al.. Simple high-cell density fed-batch technique for high-level recombinant protein production with Pichia pastoris: application to intracellular production of hepatitis B surface antigen[J/OL]. Microb. Cell Fact., 2009, 8: 13[2024-08-02]. .
35	GAVILANES F, GONZALEZ-ROS J M, PETERSON D L. Structure of hepatitis B surface antigen. Characterization of the lipid components and their association with the viral proteins[J]. J. Biol. Chem., 1982, 257(13): 7770-7777.
36	PARASHAR U. Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC): Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practices (ACIP)[J/OL]. Aust. J. Rural. Health, 2006, doi:10.1111/j.‍1440-1584.2007.00928.x[2024-08-02]. .
37	VESIKARI T, FINN A, VAN DAMME P, et al.. Immunogenicity and safety of a 3-antigen hepatitis B vaccine vs a single-antigen hepatitis B vaccine: a phase 3 randomized clinical trial[J/OL]. JAMA Netw. Open, 2021, 4(10): e2128652[2024-08-02]. .
38	GUPTA A K, MACLEOD M A, ABRAMOVITS W. GARDASIL 9 (human papillomavirus 9-valent vaccine, recombinant)[J]. Skinmed, 2016, 14(1): 33-37.
39	HU Y M, HUANG S J, CHU K,et al.. Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine an open-label phase I clinical trial[J]. Human Vaccines Immunother., 2014, 10(2): 1-7.
40	ANASTASIA P, CYRA P, ALEXIS P, et al.. Safety of human papillomavirus vaccines: an updated review[J]. Drug Safety Int. J. Med. Toxicol. Drug Exp., 2018, 41:329-346.
41	LANINI S, GARBUGLIA A R, LAPA D, et al.. Epidemiology of HEV in the mediterranean basin: 10-year prevalence in Italy[J/OL]. BMJ Open, 2015, 5(7): e007110[2024-08-02]. .
42	WU X, CHEN P, LIN H, et al.. Hepatitis E virus: current epidemiology and vaccine[J]. Hum. Vaccin. Immunother., 2016, 12(10): 2603-2610.
43	HOLLA R P, AHMAD I, AHMAD Z, et al.. Molecular virology of hepatitis E virus[J]. Semin. Liver Dis., 2013, 33(1): 3-14.
44	BRADLEY D W. Hepatitis E virus: a brief review of the biology, molecular virology, and immunology of a novel virus[J]. J. Hepatol., 1995, 22(1 ): 140-145.
45	Robust manufacturing and comprehensive characterization of recombinant hepatitis E virus-like particles in Hecolin?[J].Vaccine, 2014, 32(32):4039-4050.
46	MAZALOVSKA M, KOUOKAM J C. Progress in the production of virus-like particles for vaccination against hepatitis E virus[J/OL]. Viruses, 2020, 12(8): 826[2024-08-02]. .
47	ARORA N, ANBALAGAN LC, PANNU A K. Towards eradication of malaria: is the WHO's RTS, S/AS01 vaccination effective enough?[J]. Risk Manag. Healthc. Policy, 2021, 14: 1033-1039.
48	CALLAWAY E. The next generation of coronavirus vaccines: a graphical guide[J]. Nature, 2023, 614(7946): 22-25.
49	THOMS F, JENNINGS G T, MAUDRICH M, et al.. Immunization of cats to induce neutralizing antibodies against Fel d 1, the major feline allergen in human subjects[J]. J. Allergy Clin. Immunol., 2019, 144(1): 193-203.
50	YILMAZ I C, IPEKOGLU E M, BULBUL A, et al.. Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection[J]. Allergy, 2022, 77(1): 258-270.
51	PILLET S, ARUNACHALAM P S, ANDREANI G, et al.. Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman Primates[J]. Cell. Mol. Immunol., 2022, 19(2): 222-233.
52	NG K K, PENDÁS-FRANCO N, ROJO J, et al.. Crystal structure of Norwalk virus polymerase reveals the carboxyl terminus in the active site cleft[J]. J. Biol. Chem., 2004, 279(16): 16638-16645.
53	JAZAYERI S D, POH C L. Development of universal influenza vaccines targeting conserved viral proteins[J/OL]. Vaccines (Basel), 2019, 7(4): 169[2024-08-02]. .
54	BUFFIN S, PEUBEZ I, BARRIÈRE F, et al.. Influenza A and B virus-like particles produced in mammalian cells are highly immunogenic and induce functional antibodies[J]. Vaccine, 2019, 37(46): 6857-6867.
55	TISSOT A C, RENHOFA R, SCHMITZ N, et al.. Versatile virus-like particle carrier for epitope based vaccines[J/OL]. PLoS One, 2010, 5(3): e9809[2024-08-02]. .
56	CHANG M O, SUZUKI T, SUZUKI H, et al.. HIV-1 Gag-virus-like particles induce natural killer cell immune responses via activation and maturation of dendritic cells[J]. J. Innate Immun., 2012, 4(2): 187-200.
57	CHANG M O, SUZUKI T, YAMAMOTO N, et al.. HIV-1 Gag-virus-like particles inhibit HIV-1 replication in dendritic cells and T cells through IFN-α-dependent upregulation of APOBEC3G and 3F[J]. J. Innate Immun., 2012, 4(5-6): 579-590.

药品名称	上市时间	抗原表位	表达系统	佐剂	生产商
Engerix-B^®	1989	S抗原	酿酒酵母	氢氧化铝	英国葛兰素史克公司
Fendrix^®	2005	S抗原	酿酒酵母	AS04	英国葛兰素史克公司
Heplisav-B^®	2017	S抗原	汉逊酵母	CpG1018	美国德纳维制药公司
Recombivax HB^®	2018	S抗原	酿酒酵母	硫酸铝	美国默沙东公司
PreHevbrio^®(Sci-B-Vac)	2021	S抗原、pre-S1抗原和pre-S2抗原	哺乳动物(CHO细胞)	氢氧化铝	美国VBI疫苗公司

药品名称	上市时间	抗原表位	表达系统	佐剂	生产商
Engerix-B^®	1989	S抗原	酿酒酵母	氢氧化铝	英国葛兰素史克公司
Fendrix^®	2005	S抗原	酿酒酵母	AS04	英国葛兰素史克公司
Heplisav-B^®	2017	S抗原	汉逊酵母	CpG1018	美国德纳维制药公司
Recombivax HB^®	2018	S抗原	酿酒酵母	硫酸铝	美国默沙东公司
PreHevbrio^®(Sci-B-Vac)	2021	S抗原、pre-S1抗原和pre-S2抗原	哺乳动物(CHO细胞)	氢氧化铝	美国VBI疫苗公司

药品名称	上市时间	抗原表位	表达系统	佐剂	生产商
Cervarix^®	2006	L1 HPV 16 L1 HPV 18	昆虫-杆状病毒	氢氧化铝ASO4	英国葛兰素史克公司
Gardasil^®	2009	L1 HPV 6 L1 HPV 11 L1 HPV 16 L1 HPV 18	酿酒酵母	羟基磷酸硫酸铝	美国默沙东公司
Gardasil9^®	2014	L1 HPV 6 L1 HPV 11 L1 HPV 16 L1 HPV 18 L1 HPV 31 L1 HPV 33 L1 HPV 45 L1 HPV 52 L1 HPV 58	酿酒酵母	羟基磷酸硫酸铝	美国默沙东公司
馨可宁^®	2019	L1 HPV 16 L1 HPV 18	大肠杆菌	氢氧化铝	厦门万泰
沃泽惠^®	2022	L1 HPV 16 L1 HPV 18	毕赤酵母	磷酸铝	沃森生物

药品名称	上市时间	抗原表位	表达系统	佐剂	生产商
Cervarix^®	2006	L1 HPV 16 L1 HPV 18	昆虫-杆状病毒	氢氧化铝ASO4	英国葛兰素史克公司
Gardasil^®	2009	L1 HPV 6 L1 HPV 11 L1 HPV 16 L1 HPV 18	酿酒酵母	羟基磷酸硫酸铝	美国默沙东公司
Gardasil9^®	2014	L1 HPV 6 L1 HPV 11 L1 HPV 16 L1 HPV 18 L1 HPV 31 L1 HPV 33 L1 HPV 45 L1 HPV 52 L1 HPV 58	酿酒酵母	羟基磷酸硫酸铝	美国默沙东公司
馨可宁^®	2019	L1 HPV 16 L1 HPV 18	大肠杆菌	氢氧化铝	厦门万泰
沃泽惠^®	2022	L1 HPV 16 L1 HPV 18	毕赤酵母	磷酸铝	沃森生物

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Research Progress of Virus-like Particles Vaccine

病毒样颗粒疫苗研究进展

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