Pseudo-rationale design of efficient TB vaccines: lesson from the mycobacterial 27-kDa lipoprotein

Tuberculosis
Avi-Hai Hovav, Herve Bercovier

Abstract

To develop or improve acellular vaccines against tuberculosis, scientists are in quest for the most efficient Th1 antigens. Immunization of mice with the M. tuberculosis 27-kDa antigen resulted in a strong Th1 immune response as indicated by serum analysis, splenocyte proliferation and cytokines secretion profile. Unexpectedly, mice immunized with 27-kDa turned out to be more susceptible to mycobacterial challenge as we found significant increase in the splenic cfu count compared to control groups. Moreover, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. Further analysis of 27-kDa revealed that this lipoprotein is a B-cell mitogen, a feature that is known to be linked to enhanced virulence of the pathogen. However, by using the non-acylated form, 27DeltaSP, we excluded the involvement of the mitogenicity of 27-kDa in its deleterious effect. Currently, there is no explanation to the fact that the 27-kDa interferes with the protective immunity of other mycobacterial antigens; however, it is clear that 27-kDa need to be excluded from any future vaccine preparations. Indeed, we developed a multivalent vaccine that consists of six...Continue Reading

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Citations

Jul 14, 2012·Immunotherapy·T Mark Doherty
Jul 14, 2012·Tuberculosis·Otmane Lamrabet, Michel Drancourt
Jan 9, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Suraj B SableG K Khuller
Apr 30, 2009·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Jes Dietrich, T Mark Doherty
Jun 20, 2008·Expert Review of Vaccines·Lan H Ly, David N McMurray

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