Skip to main content
Log in

Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Streptococcus pneumoniae is a leading cause of infectious diseases in children under 5-year-old. Vaccine has been used as an indispensable strategy to prevent S. pneumoniae infection for more than 30 years. Our previous studies confirmed that mucosal immunization with live attenuated strain SPY1 can protect mice against nasopharyngeal colonization of S. pneumoniae and lethal pneumococcal infection, and the protective effects are comparable with those induced by commercially available 23-valent polysaccharide vaccine. However, live attenuated vaccine SPY1 needs four inoculations to get satisfactory protective effect, which may increase the risk of virulence recovery. It is reported that heterologous primeboost approach is more effective than homologous primeboost approach. In the present study, to decrease the doses of live SPY1 and improve the safety of SPY1 vaccine, we immunized mice with SPY1 and DnaJ protein alternately. Our results showed that heterologous prime-boost immunization with SPY1 and DnaJ protein could significantly reduce the colonization of S. pneumoniae in the respiratory tract of mice, and induce stronger Th1 and Th17 cellular immune responses than SPY1 alone. These results indicate heterologous prime-boost immunization method not only elicits better protective effect than SPY1 alone, but also reduces the doses of live SPY1 and decreases the risk of SPY1 vaccine. This work is the first time to study the protective efficiency with two different forms of S. pneumoniae candidate vaccine, and provides a new strategy for the development of S. pneumoniae vaccine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Babb, R., Chen, A., Hirst, T.R., Kara, E.E., McColl, S.R., Ogunniyi, A.D., Paton, J.C., and Alsharifi, M. 2016. Intranasal vaccination with gamma-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses. Clin. Sci. (Lond) 130, 697–710.

    Article  CAS  Google Scholar 

  • Blair, C., Naclerio, R.M., Yu, X., Thompson, K., and Sperling, A. 2005. Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: a mouse model. J. Infect. Dis. 192, 1237–1244.

    Article  CAS  PubMed  Google Scholar 

  • Bogaert, D., de Groot, R., and Hermans, P.W.M. 2004. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect. Dis. 4, 144–154.

    Article  CAS  PubMed  Google Scholar 

  • Cui, Y., Zhang, X., Gong, Y., Niu, S., Yin, N., Yao, R., Xu, W., Li, D., Wang, H., He, Y., et al. 2011. Immunization with DnaJ (hsp40) could elicit protection against nasopharyngeal colonization and invasive infection caused by different strains of Streptococcus pneumoniae. Vaccine 29, 1736–1744.

    Article  CAS  PubMed  Google Scholar 

  • Fioretti, D., Iurescia, S., Fazio, V.M., and Rinaldi, M. 2010. DNA vaccines: developing new strategies against cancer. J. Biomed. Biotechnol. 2010, 174378.

    Article  PubMed  PubMed Central  Google Scholar 

  • Golshani, M., Rafati, S., Siadat, S.D., Nejati-Moheimani, M., Shahcheraghi, F., Arsang, A., and Bouzari, S. 2015. Improved immunogenicity and protective efficacy of a divalent DNA vaccine encoding Brucella L7/L12-truncated Omp31 fusion protein by a DNA priming and protein boosting regimen. Mol. Immunol. 66, 384–391.

    Article  CAS  PubMed  Google Scholar 

  • Jahn-Schmid, B., Messner, P., Unger, F.M., Sleytr, U.B., Scheiner, O., and Kraft, D. 1996. Toward selective elicitation of TH1-controlled vaccination responses: vaccine applications of bacterial surface layer proteins. J. Biotechnol. 44, 225–231.

    Article  CAS  PubMed  Google Scholar 

  • Li, P., Cao, R.B., Zheng, Q.S., Liu, J.J., Li, Y., Wang, E.X., Li, F., and Chen, P.Y. 2010. Enhancement of humoral and cellular immunity in mice against Japanese encephalitis virus using a DNA primeprotein boost vaccine strategy. Vet. J. 183, 210–216.

    Article  CAS  PubMed  Google Scholar 

  • Li, W., Wang, S., and Lu, S. 2013. Pilot study on the use of DNA priming immunization to enhance Y. pestis LcrV-specific B cell responses elicited by a recombinant LcrV protein vaccine. Vaccines (Basel) 2, 36–48.

    Article  Google Scholar 

  • Liu, S., Shi, D., Wang, H.C., Yu, Y.Z., Xu, Q., and Sun, Z.W. 2015. Co-immunization with DNA and protein mixture: a safe and efficacious immunotherapeutic strategy for Alzheimer’s disease in PDAPP mice. Sci. Rep. 5, 7771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, Y., Wang, H., Zhang, S., Zeng, L., Xu, X., Wu, K., Wang, W., Yin, N., Song, Z., Zhang, X., et al. 2014. Mucosal immunization with recombinant fusion protein DnaJ-DeltaA146Ply enhances crossprotective immunity against Streptococcus pneumoniae infection in mice via interleukin 17A. Infect. Immun. 82, 1666–1675.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lorin, C., Vanloubbeeck, Y., Baudart, S., Ska, M., Bayat, B., Brauers, G., Clarinval, G., Donner, M.N., Marchand, M., Koutsoukos, M., et al. 2015. Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques. PLoS One 10, e0122835.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu, S. 2009. Heterologous prime-boost vaccination. Curr. Opin. Immunol. 21, 346–351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu, S. 2011. Two is better than one. Lancet. Infect. Dis. 11, 889–891.

    Article  PubMed  Google Scholar 

  • Lu, Y.J., Gross, J., Bogaert, D., Finn, A., Bagrade, L., Zhang, Q., Kolls, J.K., Srivastava, A., Lundgren, A., Forte, S., et al. 2008. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog. 4, e1000159.

    Article  PubMed  PubMed Central  Google Scholar 

  • Magalhaes, I., Sizemore, D.R., Ahmed, R.K., Mueller, S., Wehlin, L., Scanga, C., Weichold, F., Schirru, G., Pau, M.G., Goudsmit, J., et al. 2008. rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector. PLoS One 3, e3790.

    Article  PubMed  PubMed Central  Google Scholar 

  • Moffitt, K.L. and Malley, R. 2011. Next generation pneumococcal vaccines. Curr. Opin. Immunol. 23, 407–413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mook-Kanamori, B.B., Geldhoff, M., van der Poll, T., and van de Beek, D. 2011. Pathogenesis and pathophysiology of pneumococcal meningitis. Clin. Microbiol. Rev. 24, 557–591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nand, K.N., Gupta, J.C., Panda, A.K., Jain, S.K., and Talwar, G.P. 2015. Priming with DNA enhances considerably the immunogenicity of hCG ß-LTB vaccine. Am. J. Reprod. Immunol. 74, 302.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen, C.T., Kim, S.Y., Kim, M.S., Lee, S.E., and Rhee, J.H. 2011. Intranasal immunization with recombinant PspA fused with a flagellin enhances cross-protective immunity against Streptococcus pneumoniae infection in mice. Vaccine 29, 5731–5739.

    Article  CAS  PubMed  Google Scholar 

  • O’Brien, K.L., Wolfson, L.J., Watt, J.P., Henkle, E., Deloria-Knoll, M., McCall, N., Lee, E., Mulholland, Kim, Levine, O.S., Cherian, T., et al. 2009. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374, 893–902.

    Article  PubMed  Google Scholar 

  • Pilishvili, T., Lexau, C., Farley, M.M., Hadler, J., Harrison, L.H., Bennett, N.M., Reingold, A., Thomas, A., Schaffner, W., Craig, A.S., et al. 2010. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J. Infect. Dis. 201, 32–41.

    Article  PubMed  Google Scholar 

  • Roche, A.M., King, S.J., and Weiser, J.N. 2007. Live attenuated Streptococcus pneumoniae strains induce serotype-independent mucosal and systemic protection in mice. Infect. Immun. 75, 2469–2475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigo, C. and Lim, W.S. 2014. The relevance of pneumococcal serotypes. Curr. Infect. Dis. Rep. 16, 403.

    Article  PubMed  Google Scholar 

  • Wang, Y., Jiang, B., Guo, Y., Li, W., Tian, Y., Sonnenberg, G.F., Weiser, J.N., Ni, X., and Shen, H. 2016. Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection. Mucosal Immunol. 10, 250–259.

    Article  PubMed  PubMed Central  Google Scholar 

  • Weinberger, D.M., Malley, R., and Lipsitch, M. 2011. Serotype replacement in disease after pneumococcal vaccination. Lancet 378, 1962–1973.

    Article  PubMed  PubMed Central  Google Scholar 

  • WHO. 2012. Pneumococcal vaccines WHO position paper—2012. Wkly. Epidemiol. Rec. 87, 129–144.

    Google Scholar 

  • WHO. 2013. Progress in introduction of pneumococcal conjugate vaccine worldwide, 2000–2012. Wkly. Epidemiol. Rec. 88, 173–180.

    Google Scholar 

  • Wilson, R., Cohen, J.M., Jose, R.J., de Vogel, C., Baxendale, H., and Brown, J.S. 2015. Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses. Mucosal Immunol. 8, 627–639.

    Article  CAS  PubMed  Google Scholar 

  • Wu, K., Yao, R., Wang, H., Pang, D., Liu, Y., Xu, H., Zhang, S., Zhang, X., and Yin, Y. 2014. Mucosal and systemic immunization with a novel attenuated pneumococcal vaccine candidate confer serotype independent protection against Streptococcus pneumoniae in mice. Vaccine 32, 4179–4188.

    Article  CAS  PubMed  Google Scholar 

  • Wu, K., Zhang, X., Shi, J., Li, N., Li, D., Luo, M., Cao, J., Yin, N., Wang, H., Xu, W., et al. 2010. Immunization with a combination of three pneumococcal proteins confers additive and broad protection against Streptococcus pneumoniae infections in mice. Infect. Immun. 78, 1276–1283.

    Article  CAS  PubMed  Google Scholar 

  • Xu, X., Meng, J., Wang, Y., Zheng, J., Wu, K., Zhang, X., Yin, Y., and Zhang, Q. 2014. Serotype-independent protection against pneumococcal infections elicited by intranasal immunization with ethanol-killed pneumococcal strain, SPY1. J. Microbiol. 52, 315–323.

    Article  CAS  PubMed  Google Scholar 

  • Xu, X., Wang, H., Liu, Y., Wang, Y., Zeng, L., Wu, K., Wang, J., Ma, F., Xu, W., Yin, Y., et al. 2015. Mucosal immunization with the live attenuated vaccine SPY1 induces humoral and Th2-Th17-regulatory T cell cellular immunity and protects against pneumococcal infection. Infect. Immun. 83, 90–100.

    Article  PubMed  Google Scholar 

  • Yan, W., Wang, H., Xu, W., Wu, K., Yao, R., Xu, X., Dong, J., Zhang, Y., Zhong, W., and Zhang, X. 2012. SP0454, a putative threonine dehydratase, is required for pneumococcal virulence in mice. J. Microbiol. 50, 511–517.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wenchun Xu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qiu, Y., Zhang, X., Wang, H. et al. Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice. J Microbiol. 55, 823–829 (2017). https://doi.org/10.1007/s12275-017-7262-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-017-7262-1

Keywords

Navigation