Limits...
Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.

Niu H, Peng J, Bai C, Liu X, Hu L, Luo Y, Wang B, Zhang Y, Chen J, Yu H, Xian Q, Zhu B - PLoS ONE (2015)

Bottom Line: The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge.Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination.In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.

View Article: PubMed Central - PubMed

Affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

ABSTRACT
Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.

No MeSH data available.


Related in: MedlinePlus

The immunogenicity of LT69 vaccine in mice.C57BL/6 mice were immunized with 50μg or 10μg or 2μg of LT69 formulated in DDA/Poly(I:C) separately via subcutaneous injection three times (2 weeks apart) or with a single dose of BCG (5×106 CFU). For EAMM+MH group, the mice received EAMM (10 μg) plus MH (10 μg) in DDA/Poly(I:C). Six weeks after the final immunization, spleen cells were stimulated with ESAT6 (10 xg /ml), Ag85B (5 μg/ml), Mtb10.4 (10 μg/ml), HspX (10 μg/ml) and PPD (5 μg/ml) separately in vitro. (A) The IFN-γ secretion in splenocytes. (B) The IL-2 secretion in splenocytes. Results are presented as means ± SD, n = 4. * p < 0.05, relative to PBS,BCG; ** p < 0.05, relative to PBS,BCG and EAMM+MH groups
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4476732&req=5

pone.0130641.g002: The immunogenicity of LT69 vaccine in mice.C57BL/6 mice were immunized with 50μg or 10μg or 2μg of LT69 formulated in DDA/Poly(I:C) separately via subcutaneous injection three times (2 weeks apart) or with a single dose of BCG (5×106 CFU). For EAMM+MH group, the mice received EAMM (10 μg) plus MH (10 μg) in DDA/Poly(I:C). Six weeks after the final immunization, spleen cells were stimulated with ESAT6 (10 xg /ml), Ag85B (5 μg/ml), Mtb10.4 (10 μg/ml), HspX (10 μg/ml) and PPD (5 μg/ml) separately in vitro. (A) The IFN-γ secretion in splenocytes. (B) The IL-2 secretion in splenocytes. Results are presented as means ± SD, n = 4. * p < 0.05, relative to PBS,BCG; ** p < 0.05, relative to PBS,BCG and EAMM+MH groups

Mentions: With the stimulation of ESAT6, Ag85B, Mtb8.4 or PPD in vitro, the production of IFN-γ and IL-2 by spleen cells from mice immunized with LT69 were higher than that from PBS, BCG and EAMM+MH (p < 0.05) (Fig 2). With the stimulation of HspX, the IFN-γ secretions in the group of LT69 were higher than PBS, and BCG groups, but the differences between the groups of LT69 and EAMM+MH were not obvious (Fig 2A).


Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.

Niu H, Peng J, Bai C, Liu X, Hu L, Luo Y, Wang B, Zhang Y, Chen J, Yu H, Xian Q, Zhu B - PLoS ONE (2015)

The immunogenicity of LT69 vaccine in mice.C57BL/6 mice were immunized with 50μg or 10μg or 2μg of LT69 formulated in DDA/Poly(I:C) separately via subcutaneous injection three times (2 weeks apart) or with a single dose of BCG (5×106 CFU). For EAMM+MH group, the mice received EAMM (10 μg) plus MH (10 μg) in DDA/Poly(I:C). Six weeks after the final immunization, spleen cells were stimulated with ESAT6 (10 xg /ml), Ag85B (5 μg/ml), Mtb10.4 (10 μg/ml), HspX (10 μg/ml) and PPD (5 μg/ml) separately in vitro. (A) The IFN-γ secretion in splenocytes. (B) The IL-2 secretion in splenocytes. Results are presented as means ± SD, n = 4. * p < 0.05, relative to PBS,BCG; ** p < 0.05, relative to PBS,BCG and EAMM+MH groups
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476732&req=5

pone.0130641.g002: The immunogenicity of LT69 vaccine in mice.C57BL/6 mice were immunized with 50μg or 10μg or 2μg of LT69 formulated in DDA/Poly(I:C) separately via subcutaneous injection three times (2 weeks apart) or with a single dose of BCG (5×106 CFU). For EAMM+MH group, the mice received EAMM (10 μg) plus MH (10 μg) in DDA/Poly(I:C). Six weeks after the final immunization, spleen cells were stimulated with ESAT6 (10 xg /ml), Ag85B (5 μg/ml), Mtb10.4 (10 μg/ml), HspX (10 μg/ml) and PPD (5 μg/ml) separately in vitro. (A) The IFN-γ secretion in splenocytes. (B) The IL-2 secretion in splenocytes. Results are presented as means ± SD, n = 4. * p < 0.05, relative to PBS,BCG; ** p < 0.05, relative to PBS,BCG and EAMM+MH groups
Mentions: With the stimulation of ESAT6, Ag85B, Mtb8.4 or PPD in vitro, the production of IFN-γ and IL-2 by spleen cells from mice immunized with LT69 were higher than that from PBS, BCG and EAMM+MH (p < 0.05) (Fig 2). With the stimulation of HspX, the IFN-γ secretions in the group of LT69 were higher than PBS, and BCG groups, but the differences between the groups of LT69 and EAMM+MH were not obvious (Fig 2A).

Bottom Line: The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge.Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination.In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.

View Article: PubMed Central - PubMed

Affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

ABSTRACT
Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.

No MeSH data available.


Related in: MedlinePlus