4.5 Article

Protective immunity induced by a DNA vaccine expressing eIF4A of Toxoplasma gondii against acute toxoplasmosis in mice

Journal

VACCINE
Volume 31, Issue 13, Pages 1734-1739

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2013.01.027

Keywords

Toxoplasma gondii; Toxoplasmosis; DNA vaccine; eIF4A; Protective immunity; Mice

Funding

  1. National Natural Science Foundation of China [31230073, 31172316, 31228022, 31101812]
  2. International Science and Technology Cooperation Project of Gansu Province [1204WCGA023]
  3. Science Fund for Creative Research Groups of Gansu Province [1210RJIA006]
  4. National S & T Major Program [2012ZX10004220]
  5. Special Basic Research Fund for Nonprofit Central Public Research Institutes [2012ZL081]

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Toxoplasma gondii is an obligate intracellular protozoan parasite infecting humans, mammals and birds. Eukaryotic translation initiation factor (eIF4A) is a newly identified protein associated with tachyzoite virulence. To evaluate the protective efficacy of T. gondii eIF4A, a DNA vaccine (pVAX-eIF4A) encoding T. gondii eIF4A (Tg-eIF4A) gene was constructed. The expression ability of this recombinant DNA plasmid was examined in Marc145 cells by IFA. Then, Kunming mice were intramuscularly immunized with pVAX-eIF4A and followed by challenge infection with the highly virulent T. gondii RH strain. The results showed that vaccination with pVAX-eIF4A elicited specific humoral responses, with high IgG antibody titers and specific lymphocyte proliferative responses. The cellular immune response was associated with significant production of IFN-gamma, IL-2 in Kunming mice, and a mixed IgG1/IgG2a response with predominance of IgG2a production, indicating that a Th1 type response was elicited after immunization with pVAX-eIF4A. In addition, the increase of the percentage of CD8+ T cells in lymphoid in mice suggested the activation of MHC class I restricted antigen presentation pathways. After lethal challenge, the mice vaccinated with the pVAX-eIF4A showed a significantly prolonged survival time (23.0 +/- 5.5 days) compared with control mice which died within 7 days of challenge (P < 0.05). These results demonstrate that pVAX-eIF4A could elicit strong humoral, Th1-type cellular immune responses and increase survival time of immunized mice, suggesting that eIF4A is a promising vaccine candidate against acute T. gondii infection in mice. (C) 2013 Elsevier Ltd. All rights reserved.

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