Immunogenicity and efficacy analyses of EPC002, ECA006, and EPCP009 protein subunit combinations as tuberculosis vaccine candidates

Wang, Ruihuan; Fan, Xueting; Jiang, Yi; Li, Guilian; Li, Machao; Zhao, Xiuqin; Luan, Xiuli; Deng, Yunli; Chen, Zixin; Liu, Haican; Wan, Kanglin

doi:10.1016/j.vaccine.2023.04.003

Cited by 5 publications

(6 citation statements)

References 47 publications

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“… 37 , 38 Thus, it has been widely used for the early evaluation of TB vaccine efficacy. 39 , 40 In our study, we found that vaccination with rBCG-ECD003 greatly enhances the ability of spleen lymphocytes to control Mtb growth in the long term. We observed a nearly 1.6-fold reduction in CFU compared to the BCG group.…”

Section: Discussionmentioning

confidence: 52%

Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice

Fang,

Wang,

Fan

et al. 2024

Human Vaccines & Immunotherapeutics

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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its efficacy against Mtb infection. In this study, the immune efficacy of recombination BCG (rBCG-ECD003) expressing specific antigens ESAT-6, CFP-10, and nDnaK was evaluated at different time points after immunizing BALB/c mice. The results revealed that rBCG-ECD003 induced multiple Th1 cytokine secretion including IFN-γ, TNF-α, IL-2, and IL-12 when compared to the parental BCG. Under the action of PPD or ECD003, rBCG-ECD003 immunization resulted in a significant increase in the proportion of IL-2 + and IFN-γ + IL-2 + CD4 + T cells. Importantly, rBCG-ECD003 induced a stronger long-term humoral immune response without compromising the safety of the parental BCG vaccine. By means of the protective efficacy assay in vitro , rBCG-ECD003 showed a greater capacity to inhibit Mtb growth in the long term. Collectively, these features of rBCG-ECD003 indicate long-term protection and the promising effect of controlling Mtb infection.

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Section: Discussionmentioning

confidence: 52%

Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice

Fang,

Wang,

Fan

et al. 2024

Human Vaccines & Immunotherapeutics

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“…The transformation of plasmids and the expression and purification of EPCP009 protein are described in previous articles [ 25 ]. Briefly, pET43.1a-009 was transformed into E. coli BL21 (DE3).…”

Section: Methodsmentioning

confidence: 99%

“…The nine cytokines (IFN-γ, IL-2, TNF-α, IL-17, GM-CSF, IL-12, IL-4, IL-6, and IL-10) representing different cellular immune types were detected by Luminex assay, and Th1-type cytokine IFN-γ and Th2-type cytokine IL-4 were detected by the Enzyme-linked immunospot (ELISpot) method, as previously described [ 25 ]. What is different is that the cells were stimulated with PPD and EPCP009, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The IgG, IgG1, and IgG2a antibody concentrations in the serum were measured by ELISA [ 25 ]. Briefly, 96-well ELISA plates were coated with 200 ng of the PPD or EPCP009 protein and incubated overnight at 4 °C and then were blocked with 3% skimmed milk for 2 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The primers for verifying the plasmid integration of rBCG-EPCP009 and mRNA expression levels of rBCG-EPCP009 are shown in Table 1. The transformation of plasmids and the expression and purification of EPCP009 protein are described in previous articles [25]. Briefly, pET43.1a-009 was transformed into E. coli BL21 (DE3).…”

Section: Recombinant Rbcg-epcp009 and The Fusion Protein Epcp009mentioning

confidence: 99%

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Comparison of the Immunogenicity and Efficacy of rBCG-EPCP009, BCG Prime-EPCP009 Booster, and EPCP009 Protein Regimens as Tuberculosis Vaccine Candidates

Wang,

Fan,

et al. 2023

Vaccines

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Bacillus Calmette–Guérin (BCG) is the only widely used prophylactic tuberculosis (TB) vaccine that can prevent severe TB in infants. However, it provides poor protection in adults, and therefore, there is ongoing research into new TB vaccines and immunization strategies with more durable immune effects. The recombinant BCG and BCG prime-protein booster are two important vaccine strategies that have recently been developed based on BCG and could improve immune responses. In this study, three immune strategies based on four protective antigens, namely, ESAT-6, CFP-10, nPPE18, and nPstS1, were applied to construct recombinant rBCG-EPCP009, EPCP009 subunit protein, and BCG prime-EPCP009 booster vaccine candidates. The short- and long-term immune effects after vaccination in Balb/c mice were evaluated based on humoral immunity, cellular immunity, and the ability of spleen cells to inhibit in vitro mycobacterial growth. At 8 and 12 weeks after the initial immunization, splenocytes from mice inoculated with the BCG prime-EPCP009 protein booster secreted higher levels of PPD- and EPCP009-specific IFN-γ, IL-2, TNF-α, IL-17, GM-CSF, and IL-12 and had a higher IFN-γ+CD4+ TEM:IL-2+CD8+ TCM cell ratio than splenocytes from mice inoculated with the rBCG-EPCP009 and EPCP009 proteins. In addition, the EPCPE009-specific IgG2a/IgG1 ratio was slightly higher in the BCG prime-EPCP009 protein booster group than in the other two groups. The in vitro mycobacterial inhibition assay showed that the splenocytes of mice from the BCG prime-EPCP009 protein booster group exhibited stronger inhibition of Mycobacterium tuberculosis (M. tuberculosis) growth than the splenocytes of mice from the other two groups. These results indicate that the BCG prime-EPCP009 protein booster exhibited superior immunogenicity and M. tuberculosis growth inhibition to the parental BCG, rBCG-EPCP009, and EPCP009 proteins under in vitro conditions. Thus, the BCG prime-EPCP009 protein booster may be important for the development of a more effective adult TB vaccine.

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Optimizing antigen selection for the development of tuberculosis vaccines

Yang,

Chen,

Xia

2024

Cell Insight

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Immunogenicity and efficacy analyses of EPC002, ECA006, and EPCP009 protein subunit combinations as tuberculosis vaccine candidates

Cited by 5 publications

References 47 publications

Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice

Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice

Comparison of the Immunogenicity and Efficacy of rBCG-EPCP009, BCG Prime-EPCP009 Booster, and EPCP009 Protein Regimens as Tuberculosis Vaccine Candidates

Optimizing antigen selection for the development of tuberculosis vaccines

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