期刊论文详细信息
BMC Immunology
Adjuvant effect of docetaxel on the immune responses to influenza A H1N1 vaccine in mice
Songhua Hu2  Yu Chen3  Fei Su2  Qing Fan2  Lin Yuan1  Jian Chen2 
[1] Institute of Microbiology, Academy of Jiangxi Province, Nanchang, Jiangxi, 330029, China;Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China;Center of Experimental Animals, Zhejiang Academy of Chinese Materia Medica, Hangzhou, Zhejiang, 310007, China
关键词: Th1/Th2;    H1N1;    Influenza;    Adjuvant;    Docetaxel;   
Others  :  1077900
DOI  :  10.1186/1471-2172-13-36
 received in 2011-11-26, accepted in 2012-05-01,  发布年份 2012
PDF
【 摘 要 】

Background

Vaccination remains one of the most effective approaches to prevent the spread of infectious diseases. Immune responses to vaccination can be enhanced by inclusion of adjuvant in a vaccine. Paclitaxel extracted from the bark of the Pacific yew tree Taxus brevifola was previously demonstrated to have adjuvant property. Compared to paclitaxel, docetaxel is another member of taxane family, and is more soluble in water and easier to manipulate in medication. To investigate the adjuvant effect of this compound, we measured the immune responses induced by co-administration of a split inactivated influenza H1N1 vaccine antigen with docetaxel.

Results

When co-administered with docetaxel, lower dose antigen (equivalent to 10 ng HA) induced similar levels of IgG and IgG isotypes as well as HI titers to those induced by higher dose antigen (equivalent to 100 ng HA). Docetaxel promoted splenocyte responses to H1N1 antigen, ConA and LPS, mRNA expressions of cytokines (IFN-gamma, IL-12, IL-4 and IL-10) and T-bet/GATA-3 by splenocytes. The enhanced immunity was associated with up-expressed microRNAs (miR-155, miR-150 and miR-146a) in docetaxel-stimulated RAW264.7 cells. Docetaxel promoted similar IgE level to but alum promoted significantly higher IgE level than the control.

Conclusion

Docetaxel has adjuvant effect on the influenza H1N1 vaccine by up-regulation of Th1/Th2 immune responses. Considering its unique vaccine adjuvant property as well as the safe record as an anti-neoplastic agent clinically used in humans during a long period, docetaxel should be further studied for its use in influenza vaccine production.

【 授权许可】

   
2012 Chen et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20141114155250997.pdf 1333KB PDF download
Figure 7. 160KB Image download
Figure 6. 69KB Image download
Figure 5. 31KB Image download
Figure 4. 66KB Image download
Figure 3. 32KB Image download
Figure 2. 55KB Image download
Figure 1. 26KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】
  • [1]Barry DW, Mayner RE, Staton E, Dunlap RC, Rastogi SC, Hannah JE, Blackburn RJ, Nortman DF, Graze PR: Comparative trial of influenza vaccines. I. Immunogenicity of whole virus and split product vaccines in man. Am J Epidemiol 1976, 104:34-46.
  • [2]Couch RB: Seasonal inactivated influenza virus vaccines. Vaccine 2008, 26(Suppl 4):D5-D9.
  • [3]Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, Burke DS: Strategies for mitigating an influenza pandemic. Nature 2006, 442:448-452.
  • [4]Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM: Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009, 361:1945-1952.
  • [5]Kieny MP, Costa A, Hombach J, Carrasco P, Pervikov Y, Salisbury D, Greco M, Gust I, LaForce M, Franco-Paredes C, Santos JI, D’Hondt E, Rimmelzwaan G, Karron R, Fukuda K: A global pandemic influenza vaccine action plan. Vaccine 2006, 24:6367-6370.
  • [6]World Health Organization: Antigenic and genetic characteristics of influenza A (H5N1) and influenza A (H9N2) viruses and candidate vaccine viruses developed for potential use in human vaccines. 2010. Available: http://www.who.int/influenza/resources/documents/201002_H5_H9_VaccineVirusUpdate.pdf webcite
  • [7]Hu AY, Weng TC, Tseng YF, Chen YS, Wu CH, Hsiao S, Chou AH, Chao HJ, Gu A, Wu SC, Chong P, Lee MS: Microcarrier-based MDCK cell culture system for the production of influenza H5N1 vaccines. Vaccine 2008, 26:5736-5740.
  • [8]Schubert C: Boosting our best shot. Nature Medicine 2009, 15:984-988.
  • [9]Kistner O, Howard MK, Spruth M, Wodal W, Bruhl P, Gerencer M, Crowe BA, Savidis-Dacho H, Livey I, Reiter M, Mayerhofer I, Tauer C, Grillberger L, Mundt W, Falkner FG, Barrett PN: Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses. Vaccine 2007, 25:6028-6036.
  • [10]Ninomiya A, Imai M, Tashiro M, Odagiri T: Inactivated influenza H5N1 whole-virus vaccine with aluminum adjuvant induces homologous and heterologous protective immunities against lethal challenge with highly pathogenic H5N1 avian influenza viruses in a mouse model. Vaccine 2007, 25:3554-3560.
  • [11]Gupta RK: Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 1998, 32:155-172.
  • [12]Podda A, Giudice GD: MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile. Expert Rev Vaccines 2003, 2:197-203.
  • [13]Podda A: The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine 2001, 19:2673-2680.
  • [14]Parretta E, Ianniello B, Ferrazin F, Rossi F, Capuano A: Italian post-marketing surveillance for adverse event reports after MF59-adjuvanted H1N1v vaccination. Vaccine 2011, 29:3708-3713.
  • [15]Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT: Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971, 93:2325-2327.
  • [16]Schiff PB, Fant J, Horwitz SB: Promotion of microtubule assembly in vitro by taxol. Nature 1979, 277:665-667.
  • [17]Abal M, Andreu JM, Barasoain I: Taxanes: microtubule and centrosome targets, and cell cycle dependent mechanisms of action. Curr Cancer Drug Targets 2003, 3:193-203.
  • [18]Tankanow RM: Docetaxel: a taxoid for the treatment of metastatic breast cancer. Am J Health Syst Pharm 1998, 55:1777-1791.
  • [19]Rowinsky EK, Donehower RC: Paclitaxel (taxol). N Engl J Med 1995, 332:1004-1014.
  • [20]Byrd-Leifer CA, Block EF, Takeda K, Akira S, Ding A: The role of MyD88 and TLR4 in the LPS-mimetic activity of Taxol. Eur J Immunol 2001, 31:2448-2457.
  • [21]Yuan L, Wu L, Chen J, Wu Q, Hu S: Paclitaxel acts as an adjuvant to promote both Th1 and Th2 immune responses induced by ovalbumin in mice. Vaccine 2010, 28:4402-4410.
  • [22]Garnett CT, Schlom J, Hodge JW: Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res 2008, 14:3536-3544.
  • [23]Cox RJ, Hovden AO, Brokstad KA, Szyszko E, Madhun AS, Haaheim LR: The humoral immune response and protective efficacy of vaccination with inactivated split and whole influenza virus vaccines in BALB/c mice. Vaccine 2006, 24:6585-6587.
  • [24]Caillet C, Piras F, Bernard MC, de Montfort A, Boudet F, Vogel FR, Hoffenbach A, Moste C, Kusters I: AF03-adjuvanted and non-adjuvanted pandemic influenza A (H1N1) 2009 vaccines induce strong antibody responses in seasonal influenza vaccine-primed and unprimed mice. Vaccine 2010, 28:3076-3079.
  • [25]Nauta JJP, Bruijn IA: On the bias in HI titers and how to reduce it. Vaccine 2006, 24:6645-6646.
  • [26]Gross PA, Davis AE: Neutralization test in influenza: use in individuals without hemagglutination inhibition antibody. J Clin Microbiol 1979, 10:382-384.
  • [27]Crume KP, O’Sullivan D, Miller JH, Northcote PT, La Flamme AC: Delaying the onset of experimental autoimmune encephalomyelitis with the microtubule-stabilizing compounds, paclitaxel and Peloruside A. J Leukoc Biol 2009, 86:949-958.
  • [28]O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 2007, 104:1604-1609.
  • [29]Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, Rajewsky N, Bender TP, Rajewsky K: MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 2007, 131:146-159.
  • [30]Chen CZ, Li L, Lodish HF, Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science 2004, 303:83-86.
  • [31]Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G, Braich R, Manoharan M, Soutschek J, Skare P, Klein LO, Davis MM, Chen CZ: miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 2007, 129:147-161.
  • [32]Verweij J, Clavel M, Chevalier B: Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann Oncol 1994, 5:495-505.
  • [33]Bissery MC, Nohynek G, Sanderink GJ, Lavelle F: Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experience. Anticancer Drugs 1995, 6:339-355. 363–8
  • [34]Hehme N, Engelmann H, Kuenzel W, Neumeier E, Saenger R: Immunogenicity of a monovalent, aluminum-adjuvanted influenza whole virus vaccine for pandemic use. Virus Res 2004, 103:163-171.
  • [35]Hamaoka T, Katz DH, Benacerraf B: Hapten-specific IgE antibody responses in mice. II. Cooperative interactions between adoptively transferred T and B lymphocytes in the development of IgE response. J Exp Med 1973, 138:538-556.
  • [36]Seitz CS, Brocker EB, Trautmann A: Vaccination-associated anaphylaxis in adults: diagnostic testing ruling out IgE-mediated vaccine allergy. Vaccine 2009, 27:3885-3889.
  • [37]Wood JM, Schild GC, Newman RW, Seagroatt V: An improved single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen: application for potency determinations of inactivated whole virus and subunit vaccines. J Biol Stand 1977, 5:237-247.
  • [38]Song X, Chen J, Sakwiwatkul K, Li R, Hu S: Enhancement of immune responses to influenza vaccine (H3N2) by ginsenoside Re. Int Immunopharmacol 2010, 10:351-356.
  • [39]Kendal AP, Pereira MS, Skehel JJ: Hemagglutination inhibition. In Concepts and procedures for laboratory-based influenza surveillance. Edited by Kendal AP, Pereira MS, Skehel JJ. Centers for Disease Control and Prevention and Pan-American Health Organization, Atlanta; 1982:B17-B35.
  • [40]Sun J, Hu S, Song X: Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice. Vaccine 2007, 25:1114-1120.
  • [41]Bustin SA: Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol 2000, 25:169-193.
  • [42]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001, 25:402-408.
  • [43]Purcell MK, Kurath G, Garver KA, Herwig RP, Winton JR: Quantitative expression profiling of immune response genes in rainbow trout following infectious haematopoietic necrosis virus (IHNV) infection or DNA vaccination. Fish Shellfish Immunol 2004, 17:447-462.
  文献评价指标  
  下载次数:63次 浏览次数:10次