Heterologous prime-boost BCG with DNA vaccine expressing fusion antigens Rv2299c and Ag85A improves protective efficacy against Mycobacterium tuberculosis in mice

Wu, Juan; Hu, Zhidong; Lu, Shuihua; Fan, Xiao‐Yong

doi:10.3389/fmicb.2022.927031

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…The resultant multiepitope DNA-based dual vaccine was immunogenic and elicited a T cell-mediated response in vitro, but in vivo vaccinated mice developed mild lung inflammation, limiting its utility [ 33 ]. Due to the negative results, this vaccine did not enter clinical trial; however, this study put forth a newer concept of developing a dual vaccine for HIV–TB co-infection [ 81 , 82 ].…”

Section: Newer Avenues In Tb Vaccine Researchmentioning

confidence: 99%

Vaccines against Tuberculosis: Where Are We Now?

2023

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Tuberculosis (TB) is among the top 10 leading causes of death in low-income countries. Statistically, TB kills more than 30,000 people each week and leads to more deaths than any other infectious disease, such as acquired immunodeficiency syndrome (AIDS) and malaria. TB treatment is largely dependent on BCG vaccination and impacted by the inefficacy of drugs, absence of advanced vaccines, misdiagnosis improper treatment, and social stigma. The BCG vaccine provides partial effectiveness in demographically distinct populations and the prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB incidences demands the design of novel TB vaccines. Various strategies have been employed to design vaccines against TB, such as: (a) The protein subunit vaccine; (b) The viral vector vaccine; (c) The inactivation of whole-cell vaccine, using related mycobacteria, (d) Recombinant BCG (rBCG) expressing Mycobacterium tuberculosis (M.tb) protein or some non-essential gene deleted BCG. There are, approximately, 19 vaccine candidates in different phases of clinical trials. In this article, we review the development of TB vaccines, their status and potential in the treatment of TB. Heterologous immune responses generated by advanced vaccines will contribute to long-lasting immunity and might protect us from both drug-sensitive and drug-resistant TB. Therefore, advanced vaccine candidates need to be identified and developed to boost the human immune system against TB.

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Section: Newer Avenues In Tb Vaccine Researchmentioning

confidence: 99%

Vaccines against Tuberculosis: Where Are We Now?

2023

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A dose escalation study to evaluate the safety of an aerosol BCG infection in previously BCG-vaccinated healthy human UK adults

Fredsgaard-Jones,

Harris,

Morrison

et al. 2024

Front. Immunol.

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IntroductionTuberculosis (TB) is the leading cause of death worldwide from a single infectious agent. Bacillus Calmette-Guérin (BCG), the only licensed vaccine, provides limited protection. Controlled human infection models (CHIMs) are useful in accelerating vaccine development for pathogens with no correlates of protection; however, the need for prolonged treatment makes Mycobacterium tuberculosis an unethical challenge agent. Aerosolised BCG provides a potential safe surrogate of infection. A CHIM in BCG-vaccinated as well as BCG-naïve individuals would allow identification of novel BCG-booster vaccine candidates and facilitate CHIM studies in populations with high TB endemicity. The purpose of this study was to evaluate the safety and utility of an aerosol BCG CHIM in historically BCG-vaccinated volunteers.MethodsThere were 12 healthy, historically BCG-vaccinated UK adults sequentially enrolled into dose-escalating groups. The first three received 1 × 104 CFU aerosol BCG Danish 1331 via a nebuliser. After safety review, subsequent groups received doses of 1 × 105 CFU, 1 × 106 CFU, or 1 × 107 CFU. Safety was monitored through self-reported adverse events (AEs), laboratory tests, and lung function testing. Immunology blood samples were taken pre-infection and at multiple timepoints post-infection. A bronchoalveolar lavage (BAL) taken 14 days post-infection was analysed for presence of live BCG.ResultsNo serious AEs occurred during the study. Solicited systemic and respiratory AEs were frequent in all groups, but generally short-lived and mild in severity. There was a trend for more reported AEs in the highest-dose group. No live BCG was detected in BAL from any volunteers. Aerosol BCG induced potent systemic cellular immune responses in the highest-dose group 7 days post-infection.DiscussionAerosol BCG infection up to a dose of 1 × 107 CFU was well-tolerated in historically BCG-vaccinated healthy, UK adults. No live BCG was detected in the BAL fluid 14 days post-infection despite potent systemic responses, suggesting early clearance. Further work is needed to expand the number of volunteers receiving BCG via the aerosol route to refine and establish utility of this aerosol BCG CHIM.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04777721.

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Immunoinformatic design of a multivalent vaccine against Brucella abortus and its evaluation in a murine model using a DNA prime-protein boost strategy

Molina,

Osorio,

Flores-Concha

et al. 2024

Front. Immunol.

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IntroductionThe development of effective vaccines against Brucella abortus is critical due to its significant impact on human and animal health. The objective of this study was to design and evaluate in silico and in vivo a multivalent vaccine based on the immunogenic potential of three selected open reading frames (ORFs) of Brucella.MethodsThe designed construct, named S22, was analyzed in silico to evaluate its physicochemical properties, antigenicity, allergenicity and toxicity. This construct was modeled and subjected to molecular dynamics analysis. Additionally, the antigenicity and protection induced by this construct was evaluated through In vivo assays immunizing BALB/c mice with protein (S22), DNA (pVS22) and combining both vaccine formats using a prime boost immunization strategy.ResultsAll bioinformatics analyses showed safe and high quality structural features, revealing favorable interactions between S22 and the TLR4/MD2 complex. Moreover, results from in vivo assays indicated that the S22 protein induced robust levels of IgG1 and IgG2a, suggesting a balanced Th1 and Th2 immune response. The DNA construct (pVS22) elicited primarily a Th1 response, whereas the use of a prime boost strategy, which combines both formats resulted in a balanced immune response with significant induction of lymphoproliferation and elevated.DiscussionAlthough our assays did not demonstrate the induction of a substantial protective response against B. abortus, this construct was capable of inducing immunogenicity. This study highlights the utility of in silico design for predicting and optimizing candidate vaccines and underscores the potential of using strategies such as prime boost, which incorporate antigens of different biological nature to modulate the immune response, while balancing parameters such as stability of the antigens and the cost of production.

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Heterologous prime-boost BCG with DNA vaccine expressing fusion antigens Rv2299c and Ag85A improves protective efficacy against Mycobacterium tuberculosis in mice

Cited by 3 publications

References 37 publications

Vaccines against Tuberculosis: Where Are We Now?

Vaccines against Tuberculosis: Where Are We Now?

A dose escalation study to evaluate the safety of an aerosol BCG infection in previously BCG-vaccinated healthy human UK adults

Immunoinformatic design of a multivalent vaccine against Brucella abortus and its evaluation in a murine model using a DNA prime-protein boost strategy

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