Boosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection

Muflihah, Heni; Florido, Mário; Lin, Chung-Cherng; Xia, Yingju; Triccas, James A.; Stambas, John; Britton, Warwick J.

doi:10.1371/journal.pone.0259829

Cited by 4 publications

(2 citation statements)

References 57 publications

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“…Another study reported using recombinant influenza A viruses (rIVAs) expressing an immune-dominant M. tuberculosis CD4 + T cell epitope (PR8-p25 and X31-p25) as a booster vaccine for BCG, which increased the frequency of specific IFN-γ-secreting T cells and polyfunctional CD4 + T cells in the lungs. However, that vaccine did not significantly increase protection against M. tuberculosis . Validation of protective efficacy is a vital prerequisite for clinical trials of novel vaccines.…”

Section: Discussionmentioning

confidence: 95%

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Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG

Mao

Wang

et al. 2023

ACS Infect. Dis.

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The resuscitation of dormant Mycobacterium tuberculosis is an important cause of adult tuberculosis (TB) transmission. According to the interaction mechanism between M. tuberculosis and the host, the latency antigen Rv0572c and region of difference 9 (RD9) antigen Rv3621c were selected in this study to prepare the fusion protein DR2. Stimulating clinically diagnosed active tuberculosis infections (i.e., TB patients), latent tuberculosis infections, and healthy controls confirmed that T lymphocytes could recognize DR2 protein in the peripheral blood of TB-infected individuals more than subcomponent protein. The DR2 protein was then emulsified in the liposome adjuvant dimethyl dioctadecyl ammonium bromide, and imiquimod (DIMQ) was administered to C57BL/6 mice immunized with Bacillus Calmette-Guérin (BCG) vaccine to evaluate their immunogenicity. Studies have shown that DR2/DIMQ, a booster vaccine for BCG primary immunization, can elicit robust CD4+ Th1 cell immune response and predominant IFN-γ+ CD4+ effector memory T cells (TEM) subsets. Furthermore, the serum antibody level and the expression of related cytokines increased significantly with the extension of immunization time, with IL2+, CD4+, or CD8+ central memory T cells (TCM) subsets predominant in the long term. This immunization strategy showed matched prophylactic protective efficacy by performing in vitro challenge experiment. This result provides robust evidence that the novel subunit vaccine prepared by fusion protein DR2 combined with liposomal adjuvant DIMQ is a promising TB vaccine candidate for further preclinical trials as a booster vaccine for BCG.

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Section: Discussionmentioning

confidence: 95%

“…However, that vaccine did not significantly increase protection against M. tuberculosis. 67 Validation of protective efficacy is a vital prerequisite for clinical trials of novel vaccines. Here, the primary splenocytes of mice in each immune group were extracted and challenged with M. tuberculosis in vitro.…”

Section: ■ Discussionmentioning

confidence: 99%

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG

Mao

Wang

et al. 2023

ACS Infect. Dis.

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Chitosan-Based Nanomaterial as Immune Adjuvant and Delivery Carrier for Vaccines

et al. 2022

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With the support of modern biotechnology, vaccine technology continues to iterate. The safety and efficacy of vaccines are some of the most important areas of development in the field. As a natural substance, chitosan is widely used in numerous fields—such as immune stimulation, drug delivery, wound healing, and antibacterial procedures—due to its good biocompatibility, low toxicity, biodegradability, and adhesion. Chitosan-based nanoparticles (NPs) have attracted extensive attention with respect to vaccine adjuvants and delivery systems due to their excellent properties, which can effectively enhance immune responses. Here, we list the classifications and mechanisms of action of vaccine adjuvants. At the same time, the preparation methods of chitosan, its NPs, and their mechanism of action in the delivery system are introduced. The extensive applications of chitosan and its NPs in protein vaccines and nucleic acid vaccines are also introduced. This paper reviewed the latest research progress of chitosan-based NPs in vaccine adjuvant and drug delivery systems.

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Tuberculosis Coinfection among COVID-19 Patients: Clinical Presentation and Mortality in a Tertiary Lung Hospital in Indonesia

Muflihah,

Yulianto,

Rina

et al. 2024

The International Journal of Mycobacteriology

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Background: Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are the top two killers of infectious disease. We aimed to determine the association of TB coinfection with the inhospital mortality of COVID-19 patients in Indonesia as a TB-endemic country. Methods: We conducted a retrospective cohort study in a tertiary lung hospital in Indonesia. All TB-coinfected COVID-19 patients who were hospitalized between January 2020 and December 2021 were included in the study. COVID-19 patients without TB were randomly selected for the control group. Clinical characteristics and laboratory results were assessed. Survival analysis was performed to determine the estimated death rate and median survival time (MST). Multivariate Cox regression analysis was conducted to define the association of TB coinfection with the in-hospital mortality of COVID-19. Results: We included 86 (8.3%) TB coinfections among 1034 confirmed COVID-19 patients. TB coinfection patients had younger age, malnutrition, and different symptoms compared to the COVID-19 group. TB-coinfected patients had a lower estimated death rate than the COVID-19 group (6.5 vs. 18.8 per 1000 population). MST in the COVID-19 group was 38 (interquartile range 16–47) days, whereas the same observation time failed to determine the MST in the TB coinfection group. TB coinfection had a crude hazard ratio of mortality 0.37 (95% confidence interval [CI] 0.15–0.94, P = 0. 004). The final model analysis including age, sex, and lymphocyte as confounding factors resulted in an adjusted HR of mortality 0.31 (95% CI 0.1–0.9). Conclusion: This study showed TB coinfection was negatively associated with the in-hospital mortality of COVID-19.

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Boosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection

Cited by 4 publications

References 57 publications

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG

Chitosan-Based Nanomaterial as Immune Adjuvant and Delivery Carrier for Vaccines

Tuberculosis Coinfection among COVID-19 Patients: Clinical Presentation and Mortality in a Tertiary Lung Hospital in Indonesia

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