Recombinant Adenovirus Delivery of Calreticulin-ESAT-6 Produces an Antigen-Specific Immune Response but no Protection Against a Mycobacterium Tuberculosis Challenge

S. C. Esparza-Gonzalez, A. Troy, J. Troudt, M. J. Loera-Arias, Julio Villatoro Hernandez, E. Torres-Lopez, J. Ancer-Rodriguez, Y. Gutierrez-Puente, G. Munoz-Maldonado, O. Saucedo-Cardenas, R. Montes-de-Oca-Luna, A. Izzo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Bacillus CalmetteGuerin (BCG) has failed to efficaciously control the worldwide spread of the disease. New vaccine development targets virulence antigens of Mycobacterium tuberculosis that are deleted in Mycobacterium bovis BCG. Immunization with ESAT-6 and CFP10 provides protection against M. tuberculosis in a murine infection model. Further, previous studies have shown that calreticulin increases the cell-mediated immune responses to antigens. Therefore, to test whether calreticulin enhances the immune response against M. tuberculosis antigens, we fused ESAT-6 to calreticulin and constructed a recombinant replication-deficient adenovirus to express the resulting fusion protein (AdCRTESAT-6). The adjuvant effect of calreticulin was assayed by measuring cytokine responses specific to ESAT-6. Recombinant adenovirus expressing the fusion protein produced higher levels of interferon-gamma and tumour necrosis factor-a in response to ESAT-6. This immune response was not improved by the addition of CFP-10 to the CRT-ESAT-6 fusion protein (AdCRTESAT-6CFP10). Mice immunized with these recombinant adenoviruses did not decrease the mycobacterial burden after low-dose aerosol infection with M. tuberculosis. We conclude that calreticulin can be used as an adjuvant to enhance the immune response against mycobacterial antigens, but it is not enough to protect against tuberculosis.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalScandinavian journal of immunology
Volume75
Issue number3
DOIs
Publication statusPublished - Mar-2012

Keywords

  • RESPIRATORY MUCOSAL IMMUNIZATION
  • FUSION PROTEIN
  • PULMONARY TUBERCULOSIS
  • ENCODING CALRETICULIN
  • VECTORED TUBERCULOSIS
  • VACCINE
  • ESAT-6
  • EPITOPE
  • DNA
  • ENHANCEMENT

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