Immunogenicity of a fusion protein containing immunodominant epitopes of Ag85C, MPT51, and HspX from Mycobacterium tuberculosis in mice and active TB infection.

PLoS One. 2012;7(10):e47781.

de Sousa EM, da Costa AC, Trentini MM, de Araújo Filho JA, Kipnis A, Junqueira-Kipnis AP.

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

Abstract

Tuberculosis (TB) remains a major global health problem. The only vaccine against tuberculosis, attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease in adults. More effective vaccines and better therapies are urgently needed to reduce the global spread of TB. This study evaluated the immunogenicity of a recombinant M. tuberculosis Ag85C-MPT51-HspX fusion protein (CMX) in mice and individuals with active tuberculosis. BALB/c mice were immunized with the CMX protein liposome-encapsulated with CpG DNA or with CpGDNA liposome-encapsulated, liposome or saline as negative controls. The immunization produced high levels of anti-CMX -specific IgG1 and IgG2a antibodies and induced an increase in the relative and absolute numbers of specific TCD4 IFN-γ(+) and TNF-α(+) cells in the spleen. Sera from a cohort of individuals with active tuberculosis contained higher levels of IgG and IgM that recognized CMX when compared to healthy individuals. In conclusion, this protein was shown to be immunogenic both in mice and humans.

PMID: 23133523

 

Supplementary information

Although tuberculosis (TB) is a treatable infectious disease and a vaccine has been in use for about 100 years, more than one million of deaths occur every year due to TB. Several laboratories have spent the last 20 years in search for a new vaccine to TB. Our laboratory in Central Brazil has been focusing in identifying molecules/ biomarkers that could distinguish between active TB, latent TB and control individuals. This is a very difficult task, especially in endemic country where other environmental and pathogenic Mycobacteria co-exist. The group believes that in order to produce a good vaccine, we need to first identify what are the main antigens produced during the different phases of the infection, and then select only the antigens that is not recognized by the immune response of patients with other mycobacterioses or by healthy individuals

In this regard this paper shows a fusion protein that was combined by three different antigens. One being the Ag85 complex that is recognized at the early stages of experimental TB infection and by T cells from TB patients. The other antigen: HspX, is recognized by individuals with latent TB. Finally, MPT51 that is recognized by T cells and antibodies from active and chronic phase of TB was also used. The novelty of this vaccine was the antigens selected based upon antigenicity between active and latent TB and the use of immunodominant epitopes.

Due to its originality for Public Healthy this work conquered a prize from Sanofi Laboratories and Medical Services on December 2012.

The novelty and promising applications of this recombinant protein, called CMX, encouraged us to test it in the mouse model of infection and when a recombinant M. smegmatis was used as vector, this vaccine showed better protection than BCG, the actual vaccine for tuberculosis.

 

Ana Paula Junqueira-Kipnis

Figure shows the authors: Monalisa M. Trentini, André Kipnis, Ana Paula (myself), Adeliane Castro Costa and Eduardo Martins de Sousa.

This study was supported by CNPq, CAPES and FAPEG.

 

Contact information:

Dr Ana Paula Junqueira-Kipnis, DVM, PhD

Associate Professor

Laboratório de Imunopatologia das Doenças infecciosas/ Laboratory of Infeccious Diseases Immunopathology.

Universidade Federal de Goiás/Federal University of Brazil

Rua 235 esquina com Primeira Avenida. Setor Universitário.

Goiânia-Goiás, Brazil. 74605-050

 

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