Hindawi Publishing Corporation
BioMed Research International
Volume 2013, Article ID 316304, 8 pages
http://dx.doi.org/10.1155/2013/316304
Research Article
Oral Immunogenicity of Plant-Made Mycobacterium
tuberculosis ESAT6 and CFP10
Elena A. Uvarova,
1
Pavel A. Belavin,
1
Natalya V. Permyakova,
1
Alla A. Zagorskaya,
1
Olesya V. Nosareva,
1,2
Almagul A. Kakimzhanova,
3
and Elena V. Deineko
1
1
Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, pr. Lavrentieva 10, Novosibirsk 630090, Russia
2
State Research Center of Virology and Biotechnology Vector, Koltsovo, Novosibirsk Oblast 630559, Russia
3
National Center of Biotechnology, ul. Valikhanova 13/1, Astana 010000, Kazakhstan
Correspondence should be addressed to Elena V. Deineko; deineko@bionet.nsc.ru
Received 12 June 2013; Accepted 28 November 2013
Academic Editor: Armando Acosta
Copyright © 2013 Elena A. Uvarova et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Two lines of transgenic carrot plants producing Mycobacterium tuberculosis proteins (ESAT6 and CFP10) have been constructed.
Te target proteins are present in carrot storage roots at a level not less than 0.056% of the total storage protein (TSP) for ESAT6 and
0.002% of TSP for CFP10. As has been shown, oral immunization of mice induces both the cell-mediated and humoral immunities.
Tese data suggest that the proteins in question are appropriate as a candidate edible vaccine against tuberculosis.
1. Introduction
Te tuberculosis caused by the bacterium Mycobacterium
tuberculosis is currently a topical problem in many countries
of the world. Recently, the number of tuberculosis cases,
including fatal outcomes, has been ever increasing [1]. Te
recorded dynamics of tuberculosis morbidity are complicated
by the spread HIV and hepatitis, ascribed by the WHO to
socially signifcant diseases [2].
To control tuberculosis, the Bacillus Calmette-Guerin
(BCG) vaccine—a live attenuated M. bovis strain [3]—was
designed as early as the 1920s; by the end of the 20th century,
about 3 billion persons worldwide had been vaccinated [4, 5].
Note that the genome of all the M. bovis BCG strains lacks
the RD1 region, characteristic of M. tuberculosis; this region
houses very important virulence factors, such as ESAT6 and
CFP10 [6, 7]. Despite the facts that BCG as a prevention
vaccine is used for protection of uninfected children and
is inefcient for adults for the most abundant tuberculosis
form, lung tuberculosis, BCG still remains the only available
vaccine against tuberculosis [3].
For tuberculosis prevention, the eforts of numerous
research groups are currently directed to design and creation
of new generation antituberculosis vaccines [8]. Over ten
candidate vaccines and one therapeutic vaccine against tuber-
culosis are now at diferent stages of clinical trials [2, 3]. Most
of them are subunit vaccines; in general, they can be divided
into two groups, namely, the vaccines for primary prevention
(intended to replace BCG) and booster vaccines (used for
revaccination). Te booster vaccines are necessary to prevent
reactivation of the pathogen during latent tuberculosis [9].
Secreted M. tuberculosis proteins are used in designing
booster vaccines; the most important of them are the proteins
that interfere with the integral components in the protection
against tuberculosis, that is, those able to induce a strong T-
cell response and -interferon secretion [10–12]. Te ESAT6
and CFP10 proteins are among the key cell virulence factors
of M. tuberculosis. Tey do induce a strong T-cell response
and, presumably, are involved in the lysis of the host cell
membrane or the overall host cell. Tese proteins are secreted
by the ESX-1 system, comprising at least ten genes (Rv3868–
Rv3877 ). Under in vitro conditions, the purifed recombinant