Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

Virology Journal

Dexin Li¹  Mengfeng Li²  Lifang Jiang²  Quanfu Zhang¹  Fushun Zhang¹  Li Zhang¹  Cong Jin¹  Xiaofang Wang¹  Fang Miao¹  Chuan Li¹  Wen Gu¹  Mifang Liang¹  Shuo Zhang¹ 

[1] State Key Laboratory for Molecular Virology and Genetic Engineering, Institute for Viral Disease Control and Prevention, China CDC, 155 Chang Bai Road, Chang Ping District, Beijing 102206, China;Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China

关键词: Vaccine;    VLP;    Dengue virus;   

Others  :  1156479
DOI  :  10.1186/1743-422X-8-333

 received in 2011-04-20, accepted in 2011-06-30,  发布年份 2011

【 摘 要 】

Background

The incidence of dengue, an infectious disease caused by dengue virus (DENV), has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs) has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated.

Results

By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses.

Conclusions

Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

【 授权许可】

   
2011 Zhang et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Ramanathan MP, Kuo YC, Selling BH, et al.: Development of a novel DNA SynCon™ tetravalent dengue vaccine that elicitsimmune responses against four serotypes. Vaccine 2009, 27:6444-53.
• [2]Centers for Disease Control and Prevention (CDC) DoV-bID-DF [http://cdc.gov/ncidod/dvbid/dengue] webcite [cited]
• [3]Chambers TJ, Hahn CS, Galler R, et al.: Flavivirus genome organization, expression, and replication. Ann Rev Microbiol 1990, 44:649-88.
• [4]Sabchareon A, Lang J, Chanthavanich P, et al.: Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration, ratio, and multiple doses. Am J Trop Med Hyg 2002, 66:264-72.
• [5]Sabchareon A, Lang J, Chanthavanich P, et al.: Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children. Pediatr Infect Dis J 2004, 23:99-109.
• [6]Edelman R, Wasserman SS, Bodison SA, et al.: Phase I trial of 16 formulations of a tetravalent live-attenuated dengue vaccine. Am J Trop Med Hyg 2003, 69:48-60.
• [7]Innis BL, Eckels KH: Progress in development of a live-attenuated, tetravalent dengue virus vaccine by the United States Army Medical Research and Materiel Command. Am J Trop Med Hyg 2003, 69:1-4.
• [8]Imoto Jun-ichi, Konishi Eiji: Dengue tetravalent DNA vaccine increases its immunogenicity in mice when mixed with a dengue type 2 subunit vaccine or an inactivated Japanese encephalitis vaccine. Vaccine 2007, 25:1076-84.
• [9]Webster DanielP, Farrar Jeremy, Rowland-Jones Sarah: Progress towards a dengue vaccine. The Lancet Infectious Diseases 2009, 9:678-87.
• [10]Galarza JM, Latham T, Cupo A: Virus-like particle (VLP) vaccine conferred complete protection against a lethal influenza virus challenge. Viral Immunol 2005, 18(1):244-51.
• [11]Li C, Liu F, Liang M, Zhang Q, et al.: Hantavirus-like particles generated in CHO cells induce specific immune responses in C57BL/6 mice. Vaccine 2010, 28:4294-4300.
• [12]Weber J, Cheinsong-Popov R, Callow D, et al.: Immunogenicity of the yeast recombinant p17/p24:Ty virus-like particles (p24-VLP) in healthy volunteers. Vaccine 1995, 13:831-4.
• [13]Sedlik C, Saron M, Sarraseca J, et al.: Recombinant parvovirus-like particles as an antigen carrier: a novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells. Proc Natl Acad Sci USA 1997, 94:7503-8.
• [14]Murata K, Lechmann M, Qiao M, et al.: Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection. Proc Natl Acad Sci USA 2003, 100:6753-8.
• [15]Pinto , Ligia A, Castle , et al.: HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood. Vaccine 2005, 23:3555-64.
• [16]Akahata Wataru, Yang Zhi-Yong, Andersen Hanne, et al.: A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nature Medicine 2010, 16:334-8.
• [17]Chang GJ, Davis BS, Hunt AR, et al.: Flavivirus DNA vaccines: current status and potential. Ann NY Acad Sci 2001, 951:272-85.
• [18]Putnak R, Porter K, Schmaljohn C: DNA vaccines for flaviviruses. Adv Virus Res 2003, 61:445-68.
• [19]Lindenbach BD, Rice CM: Flaviviridae: the viruses and their replication. In Fields Virology. 4th edition. Edited by Knipe DM, Howley PM. Philadelphia: Lippincott Williams & Willkins; 2001:991-1041.
• [20]Chang GJ, Hunt AR, Davis B: A single intramuscular injection of recombinant plasmid DNA induces protective immunity and prevents Japanese encephalitis in mice. J Virol 2000, 74:4244-52.
• [21]Lobigs Mario, Lee Eva: Inefficient Signalase Cleavage Promotes Efficient Nucleocapsid Incorporation into Budding Flavivirus Membranes. J Virol 2004, 78:178-86.
• [22]Hoke CH Jr, Malinoski FJ, Eckels KH, et al.: Preparation of an attenuated dengue 4 (341750 Carib) virus vaccine. II. Safety and immunogenicity in humans. Am J Trop Med Hyg 1990, 43:219-26.
• [23]Edelman R, Tacket CO, Wasserman SS, et al.: A live attenuated dengue-1 vaccine candidate (45AZ5) passaged in primary dog kidney cell culture is attenuated and immunogenic for humans. J Infect Dis 1994, 170:1448-55.
• [24]Staropoli I, Frenkiel MP, Megret F, et al.: Affinity-purified dengue-2 virus envelope glycoprotein induces neutralizing antibodies and protective immunity in mice. Vaccine 1997, 15:1946-54.
• [25]Simmons M, Nelson WM, Wu SJ, et al.: Evaluation of the protective efficacy of a recombinant dengue envelope B domain fusion protein against dengue 2 virus infection in mice. Am J Trop Med Hyg 1998, 58:655-62.
• [26]Bray M, Men R, Lai CJ: Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge. J Virol 1996, 70:4162-6.
• [27]Pletnev AG, Men R: Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4. Proc Natl Acad Sci USA 1998, 95:1746-51.
• [28]Kochel T, Wu SJ, Raviprakash K, et al.: Inoculation of plasmids expressing the dengue-2 envelope gene elicit neutralizing antibodies in mice. Vaccine 1997, 15:547-52.
• [29]Chang GJ, Hunt AR, Holmes DA, et al.: Enhancing biosynthesis and secretion of premembrane and envelope proteins by the chimeric plasmid of dengue virus type 2 and Japanese encephalitis virus. Virology 2003, 306:170-80.
• [30]Hsieh SC, Liu IJ, King CC, et al.: A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles Virology. 2008, 374(2):338-50.
• [31]Hsieh SC, Tsai WY, Wang WK: The length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum. J Virol 2010, 84:4782-97.
• [32]Purdy DE, Chang GJ: Secretion of noninfectious dengue virus-like particles and identification of amino acids in the stem region involved in intracellular retention of envelope protein. Virology 2005, 333:239-250.
• [33]Babu J Pradeep, Pattnaik1 Priyabrata, Gupta Nimesh, et al.: Immunogenicity of a recombinant envelope domain III protein of dengue virus type-4 with various adjuvants in mice. Vaccine 2008, 26:4655-63.
• [34]Schirmbeck R, Melber K, Kuhrober A, et al.: Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo. J Immunol 1994, 152:1110-9.
• [35]Greenstone HL, Nieland JD, de Visser KE, et al.: Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model. Proc Natl Acad Sci USA 1998, 95(4):1800-5.
• [36]Valdés I, Bernardo L, Gil L, et al.: A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice. Virology 2009, 394:249-58.