1887

Abstract

In the present study, the adjuvant activity of flagellin was compared, in the conjugated and mixed forms, against a peptide vaccine from human immunodeficiency virus type 1 (HIV-1) p24–Nef vaccine candidate. Mice were immunized with the HIV-1 p24–Nef peptide with flagellin in both conjugated and mixed forms. Lymphocyte proliferation, CTL activity, and IL-4 and IFN-γ cytokines were evaluated by bromodeoxyuridine, carboxyfluorescein succinimidyl ester and ELISA methods, respectively. At the same time, the frequency of IFN-γ-producing T-lymphocytes, as well as total and isotype-specific antibodies, were assessed by ELISPOT and indirect ELISA, respectively. Our experimental results showed that the immunized mice with the HIV-1 p24–Nef conjugated or mixed forms of flagellin led to increases in the proliferative responses and Th1 cytokine pattern. The conjugated form of vaccine led to increased CTL activity and a Th1 cytokine pattern of immune responses, as well as an IgM isotype of humoral responses in comparison with the mixed form. The flagellin-conjugated vaccine seems to be more potent in increasing vaccine immunogenicity.

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2015-11-01
2020-04-04
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References

  1. Arimilli S., Johnson J. B., Clark K. M., Graff A. H., Alexander-Miller M. A., Mizel S. B., Parks G. D. 2008; Engineered expression of the TLR5 ligand flagellin enhances paramyxovirus activation of human dendritic cell function. J Virol 82:10975–10985 [CrossRef][PubMed]
    [Google Scholar]
  2. Asadi Karam M. R., Oloomi M., Mahdavi M., Habibi M., Bouzari S. 2013; Vaccination with recombinant FimH fused with flagellin enhances cellular and humoral immunity against urinary tract infection in mice. Vaccine 31:1210–1216 [CrossRef][PubMed]
    [Google Scholar]
  3. Azmi F., Ahmad Fuaad A. A., Skwarczynski M., Toth I. 2013; Recent progress in adjuvant discovery for peptide-based subunit vaccines. Hum Vaccin Immunother 10:778–796[PubMed] [CrossRef]
    [Google Scholar]
  4. Bargieri D. Y., Leite J. A., Lopes S. C., Sbrogio-Almeida M. E., Braga C. J., Ferreira L. C., Soares I. S., Costa F. T., Rodrigues M. M. 2010; Immunogenic properties of a recombinant fusion protein containing the C-terminal 19 kDa of Plasmodium falciparum merozoite surface protein-1 and the innate immunity agonist FliC flagellin of Salmonella typhimurium . Vaccine 28:2818–2826 [CrossRef][PubMed]
    [Google Scholar]
  5. Bates J. T., Graff A. H., Phipps J. P., Grayson J. M., Mizel S. B. 2011; Enhanced antigen processing of flagellin fusion proteins promotes the antigen-specific CD8+T cell response independently of TLR5 and MyD88. J Immunol 186:6255–6262 [CrossRef][PubMed]
    [Google Scholar]
  6. Braga C. J., Massis L. M., Alencar B. C., Rodrigues M. M., Sbrogio-Almeida M. E., Ferreira L. C. 2008; Cytotoxic T cell adjuvant effects of three Salmonella enterica flagellins. Braz J Microbiol 39:44–49 [CrossRef][PubMed]
    [Google Scholar]
  7. Calarota S. A., Dai A., Trocio J. N., Weiner D. B., Lori F., Lisziewicz J. 2008; IL-15 as memory T-cell adjuvant for topical HIV-1 DermaVir vaccine. Vaccine 26:5188–5195 [CrossRef][PubMed]
    [Google Scholar]
  8. Caron G., Duluc D., Frémaux I., Jeannin P., David C., Gascan H., Delneste Y. 2005; Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-(production by memory CD4+T cells. J Immunol 175:1551–1557 [CrossRef][PubMed]
    [Google Scholar]
  9. Eom J. S., Seok Kim J., Im Jang J., Kim B. H., Young Yoo S., Hyeon Choi J., Bang I. S., Lee I. S., Keun Park Y. 2013; Enhancement of host immune responses by oral vaccination to Salmonella enterica serovar Typhimurium harboring both FliC and FljB flagella. PLoS One 8:e74850 [CrossRef][PubMed]
    [Google Scholar]
  10. Faezi S., Safarloo M., Amirmozafari N., Nikokar I., Siadat S. D., Holder I. A., Mahdavi M. 2014; Protective efficacy of Pseudomonas aeruginosa type-A flagellin in the murine burn wound model of infection. APMIS 122:115–127 [CrossRef][PubMed]
    [Google Scholar]
  11. Fakharzadeh S., Kalanaky S., Hafizi M., Goya M. M., Masoumi Z., Namaki S., Shakeri N., Abbasi M., Mahdavi M., Nazaran M. H. 2013; The new nano-complex, Hep-c, improves the immunogenicity of the hepatitis B vaccine. Vaccine 31:2591–2597 [CrossRef][PubMed]
    [Google Scholar]
  12. Gauthier M. A., Klok H. A. 2008; Peptide/protein-polymer conjugates: synthetic strategies and design concepts. Chem Commun (Camb) 23:2591–2611 [CrossRef][PubMed]
    [Google Scholar]
  13. Girard A., Roques E., Massie B., Archambault D. 2014; Flagellin in fusion with human rotavirus structural proteins exerts an adjuvant effect when delivered with replicating but non-disseminating adenovectors through the intrarectal route. Mol Biotechnol 56:394–407 [CrossRef][PubMed]
    [Google Scholar]
  14. Honko A. N., Sriranganathan N., Lees C. J., Mizel S. B. 2006; Flagellin is an effective adjuvant for immunization against lethal respiratory challenge with Yersinia pestis . Infect Immun 74:1113–1120 [CrossRef][PubMed]
    [Google Scholar]
  15. Hou B., Reizis B., DeFranco A. L. 2008; Toll-like receptors activate innate and adaptive immunity by using dendritic cell-intrinsic and -extrinsic mechanisms. Immunity 29:272–282 [CrossRef][PubMed]
    [Google Scholar]
  16. Kaisho T., Akira S. 2002; Toll-like receptors as adjuvant receptors. Biochim Biophys Acta 1589:1–13 [CrossRef][PubMed]
    [Google Scholar]
  17. Karam M. R., Oloomi M., Mahdavi M., Habibi M., Bouzari S. 2013; Assessment of immune responses of the flagellin (FliC) fused to FimH adhesin of uropathogenic Escherichia coli . Mol Immunol 54:32–39 [CrossRef][PubMed]
    [Google Scholar]
  18. Lateef S. S., Gupta S., Jayathilaka L. P., Krishnanchettiar S., Huang J. S., Lee B. S. 2007; An improved protocol for coupling synthetic peptides to carrier proteins for antibody production using DMF to solubilize peptides. J Biomol Tech 18:173–176[PubMed]
    [Google Scholar]
  19. Lee S. E., Kim S. Y., Jeong B. C., Kim Y. R., Bae S. J., Ahn O. S., Lee J. J., Song H. C., Kim J. M., other authors. 2006; A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity. Infect Immun 74:694–702 [CrossRef][PubMed]
    [Google Scholar]
  20. Li W., Li S., Hu Y., Tang B., Cui L., He W. 2008; Efficient augmentation of a long-lasting immune responses in HIV-1 gag DNA vaccination by IL-15 plasmid boosting. Vaccine 26:3282–3290 [CrossRef][PubMed]
    [Google Scholar]
  21. Mahdavi M., Ebtekar M., Mahboudi F., Khorram Khorshid H., Rahbarizadeh F., Azadmanesh K., Darabi H., Pourasgari F., Hassan Z. M. 2009; Immunogenicity of a new HIV-1 DNA construct in a BALB/c mouse model. Iran J Immunol 6:163–173[PubMed]
    [Google Scholar]
  22. Mahdavi M., Ebtekar M., Azadmanesh K., Khorramkhorshid H. R., Rahbarizadeh F., Yazdi M. H., Zabihollahi R., Abolhassani M., Hassan Z. M. 2010; HIV-1 Gag p24-Nef fusion peptide induces cellular and humoral immune response in a mouse model. Acta Virol 54:131–136 [CrossRef][PubMed]
    [Google Scholar]
  23. Mahdavi M., Ebtekar M., Khorram Khorshid H. R., Azadmanesh K., Hartoonian C., Hassan Z. M. 2011; ELISPOT analysis of a new CTL based DNA vaccine for HIV-1 using GM-CSF in DNA prime/peptide boost strategy: GM-CSF induced long-lived memory responses. Immunol Lett 140:14–20 [CrossRef][PubMed]
    [Google Scholar]
  24. Mizel S. B., Bates J. T. 2010; Flagellin as an adjuvant: cellular mechanisms and potential. J Immunol 185:5677–5682 [CrossRef][PubMed]
    [Google Scholar]
  25. Nakagawa Y., Watari E., Shimizu M., Takahashi H. 2011; One-step simple assay to determine antigen-specific cytotoxic activities by single-color flow cytometry. Biomed Res 32:159–166 [CrossRef][PubMed]
    [Google Scholar]
  26. Nguyen C. T., Hong S. H., Sin J. I., Vu H. V., Jeong K., Cho K. O., Uematsu S., Akira S., Lee S. E., Rhee J. H. 2013a; Flagellin enhances tumor-specific CD8+T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model. Vaccine 31:3879–3887 [CrossRef][PubMed]
    [Google Scholar]
  27. Nguyen C. T., Hong S. H., Ung T. T., Verma V., Kim S. Y., Rhee J. H., Lee S. E. 2013b; Intranasal immunization with a flagellin-adjuvanted peptide anticancer vaccine prevents tumor development by enhancing specific cytotoxic T lymphocyte response in a mouse model. Clin Exp Vaccine Res 2:128–134 [CrossRef][PubMed]
    [Google Scholar]
  28. Parker R. 2002; The global HIV/AIDS pandemic, structural inequalities, and the politics of international health. Am J Public Health 92:343–347 [CrossRef][PubMed]
    [Google Scholar]
  29. Pérez O., Romeu B., Cabrera O., González E., Batista-Duharte A., Labrada A., Pérez R., Reyes L. M., Ramírez W., other authors. 2013; Adjuvants are key factors for the development of future vaccines: lessons from the Finlay adjuvant platform. Front Immunol 4:407 [CrossRef][PubMed]
    [Google Scholar]
  30. Qian F., Guo A., Li M., Liu W., Pan Z., Jiang L., Wu X., Xu H. 2015; Salmonella flagellin is a potent carrier-adjuvant for peptide conjugate to induce peptide-specific antibody response in mice. Vaccine 33:2038–2044 [CrossRef][PubMed]
    [Google Scholar]
  31. Ramon G. 1924; Sur la toxine et sur l'anatoxine diphtheriques. Ann Inst Pasteur 38:1–10
    [Google Scholar]
  32. Schmid M. A., Takizawa H., Baumjohann D. R., Saito Y., Manz M. G. 2011; Bone marrow dendritic cell progenitors sense pathogens via Toll-like receptors and subsequently migrate to inflamed lymph nodes. Blood 118:4829–4840 [CrossRef][PubMed]
    [Google Scholar]
  33. Thibault S., Imbeault M., Tardif M. R., Tremblay M. J. 2009; TLR5 stimulation is sufficient to trigger reactivation of latent HIV-1 provirus in T lymphoid cells and activate virus gene expression in central memory CD4+T cells. Virology 389:20–25 [CrossRef][PubMed]
    [Google Scholar]
  34. Toyota-Hanatani Y., Inoue M., Ekawa T., Ohta H., Igimi S., Baba E. 2008; Importance of the major Fli C antigenic site of Salmonella enteritidis as a subunit vaccine antigen. Vaccine 26:4135–4137 [CrossRef][PubMed]
    [Google Scholar]
  35. Vicente-Suarez I., Brayer J., Villagra A., Cheng F., Sotomayor E. M. 2009; TLR5 ligation by flagellin converts tolerogenic dendritic cells into activating antigen-presenting cells that preferentially induce T-helper 1 responses. Immunol Lett 125:114–118 [CrossRef][PubMed]
    [Google Scholar]
  36. Yin G., Qin M., Liu X., Suo J., Tang X., Tao G., Han Q., Suo X., Wu W. 2013; An Eimeria vaccine candidate based on Eimeria tenella immune mapped protein 1 and the TLR-5 agonist Salmonella typhimurium FliC flagellin. Biochem Biophys Res Commun 440:437–442 [CrossRef][PubMed]
    [Google Scholar]
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