Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis

Belnoue, Elodie; Vogelzang, Alexis; Nieuwenhuizen, Natalie E.; Krzyzaniak, Magdalena Anna; Darbre, Stéphanie; Kreutzfeldt, Mario; Wagner, Ingrid; Merkler, Doron; Lambert, Paul‐Henri; Kaufmann, Stefan H. E.; Siegrist, Claire‐Anne; Pinschewer, Daniel D.

doi:10.3390/ijms23052700

Cited by 6 publications

(5 citation statements)

References 39 publications

(50 reference statements)

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“…CD8 + but not CD4 + T cells were efficiently boosted upon vector revaccination. According to this research, rLCMV may be helpful for adult and/or neonatal vaccination programs against pulmonary TB [79].…”

Section: Tb/flu-04lmentioning

confidence: 85%

The Use of Viral Vectors for Gene Therapy and Vaccination in Tuberculosis

Mata-Espinosa,

Lara-Espinosa,

Barrios-Payán

et al. 2023

Pharmaceuticals

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Tuberculosis (TB), an infection caused by Mycobacterium tuberculosis (Mtb), is one of the primary causes of death globally. The treatment of TB is long and based on several drugs, producing problems in compliance and toxicity, increasing Mtb resistance to first-line antibiotics that result in multidrug-resistant TB and extensively drug-resistant TB. Thus, the need for new anti-TB treatments has increased. Here, we review some model strategies to study gene therapy based on the administration of a recombinant adenovirus that encodes diverse cytokines, such as IFNγ, IL12, GM/CSF, OPN, TNFα, and antimicrobial peptides to enhance the protective immune response against Mtb. These models include a model of progressive pulmonary TB, a model of chronic infection similar to latent TB, and a murine model of pulmonary Mtb transmission to close contacts. We also review new vaccines that deliver Mtb antigens via particle- or virus-based vectors and trigger protective immune responses. The results obtained in this type of research suggest that this is an alternative therapy that has the potential to treat active TB as an adjuvant to conventional antibiotics and a promising preventive treatment for latent TB reactivation and Mtb transmission. Moreover, Ad vector vaccines are adequate for preventing infectious diseases, including TB.

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Section: Tb/flu-04lmentioning

confidence: 85%

The Use of Viral Vectors for Gene Therapy and Vaccination in Tuberculosis

Mata-Espinosa,

Lara-Espinosa,

Barrios-Payán

et al. 2023

Pharmaceuticals

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show abstract

“…Due to their high immunogenicity, LCMV vectors have been explored as vaccine candidates for various diseases (8)(9)(10). In these prior studies, LCMV vectors have been genetically modified to include a foreign antigen to prime antigen-specific immune responses.…”

Section: Lcmv Vectorsmentioning

confidence: 99%

An attenuated lymphocytic choriomeningitis virus vector enhances tumor control in mice partly via IFN-I

Chung,

Awakoaiye,

Dangi

et al. 2024

Journal of Clinical Investigation

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Viral vectors are being used for the treatment of cancer. Yet, their efficacy varies among tumors and their use poses challenges in immunosuppressed patients, underscoring the need for alternatives. We report striking antitumoral effects by a nonlytic viral vector based on attenuated lymphocytic choriomeningitis virus (r3LCMV). We show in multiple tumor models that injection of tumor-bearing mice with this vector results in improved tumor control and survival. Importantly, r3LCMV improved tumor control in immunodeficient Rag1 –/– mice and MyD88 –/– mice, suggesting that multiple pathways contributed to the antitumoral effects. The antitumoral effects of r3LCMV were also observed when this vector was administered several weeks before tumor challenges, suggesting the induction of trained immunity. Single-cell RNA sequencing analyses, antibody blockade experiments, and knockout models revealed a critical role for host-intrinsic IFN-I in the antitumoral efficacy of r3LCMV vectors. Collectively, these data demonstrate potent antitumoral effects by r3LCMV vectors and unveil multiple mechanisms underlying their antitumoral efficacy.

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“…The replication-deficient lymphocytic choriomeningitis virus (rLCMV)-based vaccine vector expressing M.tb antigens Ag85B and TB10.4 (Ag85B-TB10.4) was tested in neonatal and adult mice. It was observed that after administration, this vaccine was capable of generating heterogeneous CD4 + , CD8 + T cell populations, and lung damage was reduced when infected with M.tb [ 26 ]. rLCMV may be developed as a novel vector for delivering mycobacterial antigens.…”

Section: Description Of Various Vaccine Candidates Designed Against Tbmentioning

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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Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis

Cited by 6 publications

References 39 publications

The Use of Viral Vectors for Gene Therapy and Vaccination in Tuberculosis

The Use of Viral Vectors for Gene Therapy and Vaccination in Tuberculosis

An attenuated lymphocytic choriomeningitis virus vector enhances tumor control in mice partly via IFN-I

Vaccines against Tuberculosis: Where Are We Now?

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