Supplementation with RD antigens enhances the protective efficacy of BCG in tuberculous mice

Kalra, Mamta; Grover, Ajay; Mehta, Neena; Singh, Jaspreet; Kaur, Jaspreet; Sable, Suraj B.; Behera, Digambar; Sharma, Pawan; Verma, Indu; Khuller, G. K.

doi:10.1016/j.clim.2007.07.007

Cited by 27 publications

(21 citation statements)

References 50 publications

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“…A combined vaccine regimen of BCG and a DNA vaccine expressing the fusion protein of ESAT-6 and CFP10 might oVer greater protection against TB in cattle [23]. BCG vaccination, supplementation with the mixtures of ESAT-6, CFP21, and MPT64 proteins, also resulted in signiWcantly greater protection against experimental murine TB than BCG alone [24]. Both RD1 and RD2 are deleted in our BCG China substrain; pcD2164 and pcD610 may amplify overall anti-TB immunity in BCG immune animals by activating rCM-and rEC-speciWc T cells and play an important role in producing the booster eVect on BCG prime, as evidenced by signiWcantly increased expression of IFN-after splenocytes were restimulated with speciWc antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies including overexpression of RD1 in BCG [21] or BCG supplementation with subunit or DNA vaccine encoding RDs [22][23][24] suggested that RDs encode some important immunodominant antigens of M. tuberculosis and RD1 could enhance the protective eYcacy of BCG in the forms of recombinant BCG or subunit vaccine. The direct impact of RD2 deletion on the unstable eYcacy of diVerent BCG substrains used for vaccination has not been determined.…”

Section: Introductionmentioning

confidence: 99%

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A DNA vaccine expressing CFP21 and MPT64 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis infection in mice

Chün

Chen

et al. 2011

Med Microbiol Immunol

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The efficacy of Bacillus Calmette-Guérin (BCG) vaccine in preventing adult tuberculosis (TB) is highly variable. Genetic differences between BCG vaccine substrains, which can be divided into early strains and late strains based on the loss of region of difference two (RD2), may result in the variability and BCG substrains. The effect of lack of RD2 on the protective efficacy of BCG substrains against TB remains unknown. In this study, we demonstrated that CFP21 and MPT64(rCM) fusion protein, encoded by RD2 of Mycobacterium tuberculosis, could stimulate higher level of interferon (IFN)-γ in tuberculin skin test (TST)-positive healthy population than in TST-negative healthy population. Compared with naive mice challenged with virulent M. tuberculosis H37Rv, C57BL/6 mice vaccinated with pcD2164 DNA expressing rCM protein resulted in a greater decrease in the bacterial load of lung. Moreover, pcD2164 could boost the protective immunity in mice primed by BCG than BCG alone or DNA vaccination alone, as evidenced by lower bacterial load in the lung tissue and reduced lung pathology. The protection induced by BCG prime-DNA vaccine boost strategy was associated with significant increases in rCM protein-specific IFN-γ. Therefore, our results clearly indicate that the loss of RD2 has an important influence on the protective efficacy of different BCG substrains. These findings will benefit the optimal choice of BCG substrain for neonatal immunization and rational design of new vaccines for the prevention of TB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A DNA vaccine expressing CFP21 and MPT64 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis infection in mice

Chün

Chen

et al. 2011

Med Microbiol Immunol

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“…These data indicated that IFA may be used as one of the most optimal adjuvants for Rv3117-based vaccine studies in animal models. Studies in mouse models of TB have shown that BCG efficacy may be enhanced through supplementation with other RD antigens (39). Further studies by the authors are planned to investigate the cellular immune response induced by an Rv3117-modified BCG in C57BL/6 mice and its protective efficacy prior to or subsequent to M. tuberculosis H 37 Rv challenge.…”

Section: Discussionmentioning

confidence: 99%

Immunological evaluation of a novel Mycobacterium tuberculosis antigen, Rv3117, absent in Mycobacterium bovis BCG

Zhao¹,

Sun²,

Hao³

et al. 2013

Molecular Medicine Reports

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Abstract. Tuberculosis (TB) remains a global infectious disease.To investigate the value of a novel Mycobacterium tuberculosis (M. tuberculosis) region of difference 5 (RD5)-encoded antigen, Rv3117, in the development of effective immunodiagnostics and vaccines against TB, the immune responses to the antigen were examined in human subjects, as well as in C57BL/6 mice. The results showed that Rv3117 was able to evoke specific humoral and cellular immune responses. Consistent with the results from the RD1-encoded antigens, culture filtrate protein 10 kDa (CFP-10) and early secreted antigenic target 6 kDa (ESAT-6), the immunoglobulin G (IgG), IgM and IgA antibody responses to Rv3117 were able to statistically distinguish between the 65 patients with active pulmonary TB and the 59 healthy controls (P<0.01, respectively). In addition, higher levels of Rv3117-specific interferon-γ (IFN-γ) were observed in immunized C57BL/6 mice than in the negative control mice (P<0.05). Furthermore, high titers of total IgG, IgG1 and IgG2a antibodies were present in the sera from immunized mice, even six weeks subsequent to the immunization. In conclusion, the present results suggested that Rv3117 may be used as a candidate for the development of TB immunodiagnostics and vaccine design.

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“…In immunogenicity studies, different combinations of antigens ESAT-6/CFP-10/CFP-21/MPT-64 with BCG supplementation resulted in significantly greater protection against experimental murine TB than BCG alone. The combination of RD2 antigen only was found to release cytokines as much as substantial levels [31,32]. …”

Section: Attenuation Mechanismsmentioning

confidence: 99%

BCG vaccine in Korea

Joung

Ryoo

2013

Clin Exp Vaccine Res

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The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and the first domestic BCG vaccine was produced by the National Defense Research Institute (NDRI), current Korea Centers for Disease Control and Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was manufactured at a scale required to meet the whole amount of domestic consumption. However, since 2006, the manufacture of BCG vaccine suspended and the whole amount of BCG was imported at this point of time. Now KIT is planning to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will be render great role to National Tuberculosis Control Program (NTP) and provide initiating step for developing new tuberculosis vaccines in Korea.

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Supplementation with RD antigens enhances the protective efficacy of BCG in tuberculous mice

Cited by 27 publications

References 50 publications

A DNA vaccine expressing CFP21 and MPT64 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis infection in mice

A DNA vaccine expressing CFP21 and MPT64 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis infection in mice

Immunological evaluation of a novel Mycobacterium tuberculosis antigen, Rv3117, absent in Mycobacterium bovis BCG

BCG vaccine in Korea

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