Introduction:Bacillus Calmette–Guérin(BCG)is the only approved tuberculosis(TB)vaccine;however,it has partial efficacy and time-limited protection.Subunit booster vaccines may enhance the effects of BCG;however,...Introduction:Bacillus Calmette–Guérin(BCG)is the only approved tuberculosis(TB)vaccine;however,it has partial efficacy and time-limited protection.Subunit booster vaccines may enhance the effects of BCG;however,their efficacy depends on their composition.Methods:Six-week-old BALB/c mice received primary immunization with BCG,followed by EPCP009 protein boosters(mixed with DDA/poly:IC[DP]adjuvant)once,twice,or thrice(2-week intervals).Six weeks after the first immunization,blood and spleen samples were collected.Levels of antibodies and cytokines were assessed via enzyme-linked immunosorbent assay(ELISA),Luminex,and enzymelinked immunospot(ELISpot)The ability of splenocytes to inhibit Mycobacterium tuberculosis(Mtb)was assessed by MGIA,and pathological analyses were conducted on the liver,spleen,and lung.In addition,mice were immunized with EPCP009 or H4 protein separately.BCG was administered intravenously 6 weeks later,and spleens were collected at 3.5 weeks to quantify the BCG bacterial load.Results:BCG combined with a single EPCP009 dose provided better short-term(6-week)and longterm(12-week)protection than multiple doses.During the long-term process,the levels of purified protein derivative(PPD)-specific interferon(IFN)-γand granulocyte-macrophage colony-stimulating factor(GM-CSF)remained relatively high.No significant differences in the BCG colony counts were observed among the EPCP009/DP,phosphate-buffered saline(PBS),and DP groups.Conclusions:These findings demonstrate that BCG vaccination combined with a single dose of EPCP009 enhances protective efficacy against TB.This study provides a critical theoretical basis for designing booster immunization strategies for TB vaccines.展开更多
基金Supported by the Youth Fund for Enhancing the Capability of Infectious Disease Surveillance and Prevention(no.102393240020020000003)the Fourteenth Five-Year National Key Research and Development Program of China(no.2023YFC2307201).
文摘Introduction:Bacillus Calmette–Guérin(BCG)is the only approved tuberculosis(TB)vaccine;however,it has partial efficacy and time-limited protection.Subunit booster vaccines may enhance the effects of BCG;however,their efficacy depends on their composition.Methods:Six-week-old BALB/c mice received primary immunization with BCG,followed by EPCP009 protein boosters(mixed with DDA/poly:IC[DP]adjuvant)once,twice,or thrice(2-week intervals).Six weeks after the first immunization,blood and spleen samples were collected.Levels of antibodies and cytokines were assessed via enzyme-linked immunosorbent assay(ELISA),Luminex,and enzymelinked immunospot(ELISpot)The ability of splenocytes to inhibit Mycobacterium tuberculosis(Mtb)was assessed by MGIA,and pathological analyses were conducted on the liver,spleen,and lung.In addition,mice were immunized with EPCP009 or H4 protein separately.BCG was administered intravenously 6 weeks later,and spleens were collected at 3.5 weeks to quantify the BCG bacterial load.Results:BCG combined with a single EPCP009 dose provided better short-term(6-week)and longterm(12-week)protection than multiple doses.During the long-term process,the levels of purified protein derivative(PPD)-specific interferon(IFN)-γand granulocyte-macrophage colony-stimulating factor(GM-CSF)remained relatively high.No significant differences in the BCG colony counts were observed among the EPCP009/DP,phosphate-buffered saline(PBS),and DP groups.Conclusions:These findings demonstrate that BCG vaccination combined with a single dose of EPCP009 enhances protective efficacy against TB.This study provides a critical theoretical basis for designing booster immunization strategies for TB vaccines.
