Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c

Gunasena, Manuja; Shukla, Rajni Kant; Yao, Naiquan; Mejia, Oscar Rosas; Powell, Michael D.; Oestreich, Kenneth J; Aceves-Sánchez, Michel de Jesús; Flores-Valdéz, Mario Alberto; Liyanage, Namal P. M.; Robinson, Richard

doi:10.1038/s41598-022-14935-y

Cited by 13 publications

(9 citation statements)

References 57 publications

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“…Steigler et al showed that intranasal vaccination of mice resulted in increased levels of ILC1, ILC2, and ILC3 within lungs, 4 weeks post-immunization [ 41 ]. This is supported in future studies by Gunasena et al, showing increased levels of ILC1 and ILC3 in the tissue samples from lungs, liver, and spleen of mice 18 days post-immunization [ 71 ]. These studies have shown that BCG vaccination is involved with increased ILCs, yet there is room for further study regarding the interplay between BCG vaccination and its effects on ILCs post-infection with M. tb .…”

Section: Effects Of Bcg Vaccine On Natural Killer Cells and Innate Ly...supporting

confidence: 67%

“…Although Corral et al found that BCG vaccination showed no advantageous post-infection increase in the levels of other ILCs apart from ILC1, other studies have found there to be an increase in ILCs in response to the BCG vaccination itself [ 33 , 70 , 71 ]. Steigler et al showed that intranasal vaccination of mice resulted in increased levels of ILC1, ILC2, and ILC3 within lungs, 4 weeks post-immunization [ 41 ].…”

Section: Effects Of Bcg Vaccine On Natural Killer Cells and Innate Ly...mentioning

confidence: 99%

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Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection

et al. 2022

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is one of the leading causes of mortality due to respiratory tract infections worldwide. Infection by M. tb involves activation of a type I immune response characteristic of T helper type 1 (Th1) lymphocytes, natural killer (NK) cells, Interleukin-12 (IL-12), and interferon (IFN)-γ, all of which stimulate the activation of macrophages and robust phagocytosis in order to prevent further infectious manifestations and systemic dissemination. Recent discoveries about innate lymphoid cells (ILCs) have provided further insight about how these cells participate within the protective immune response against M. tb infection and help boost the type I immune response. In order to clearly understand the mechanisms of M. tb infection and advance the efficacy of future treatment and prevention, we must first look at the individual functions each type of immune cell plays within this process, specifically ILCs. By review of the recent literature and current evidence, our group aims to summarize the characterization of the three major groups of ILCs, including NK cells, and analyze the role that each group of ILCs play in the infectious process against M. tb in order to provide a more comprehensive understanding of the host immune response. Equally, previous studies have also highlighted the effects of how administration of the Bacille Calmette–Guérin (BCG) vaccine influences the cells and cytokines of the immune response against M. tb. Our group also aims to highlight the effects that BCG vaccine has on ILCs and how these effects provide added protection against M. tb.

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Section: Effects Of Bcg Vaccine On Natural Killer Cells and Innate Ly...supporting

confidence: 67%

Section: Effects Of Bcg Vaccine On Natural Killer Cells and Innate Ly...mentioning

confidence: 99%

Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection

et al. 2022

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“…Mtb possesses distinct mechanisms to evade our immune system, manifesting in various strategies, such as redirecting host immune responses towards tolerance and exhaustion, a characteristic also observed in other mycobacterial species, including BCG [41, 42]. Of note, BCG-elicited T cells were shown more likely to have an exhausted phenotype as compared to those elicited by BCGΔBCG1419c [43].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in vaccine induced immunity and protection againstMycobacterium tuberculosis

Parvathy,

Bhandiwad,

Eggers

et al. 2024

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Tuberculosis (TB) is a disease that has evolved with humankind for millennia, causing approximately 1.3 million deaths worldwide per annum. Although increased male affliction for TB and other infections were long known from an epidemiological perspective, our mechanistic understanding of the underlying immunological divergences is relatively recent. As such, there is insufficient knowledge regarding the sexually dimorphic immune response to TB vaccines, where no accepted correlates of protection are yet available. In this context, our goal was to explore how individual sex influences the protective effects of TB vaccines. For this purpose, we vaccinated female and male C57BL/6 mice with Bacille Calmette-Guérin (BCG) and two recombinant derivatives, VPM1002 and BCGΔBCG1419c, to analyse their protective efficacy against challenge withMycobacterium tuberculosisHN878. We found poor efficacy of BCG in males and the ability of next generation vaccine candidates to improve protection specifically in males. To determine the underlying mechanisms for the differences in survival upon vaccination between females and males, as well as, among different vaccine candidates, we analysed the distribution and persistence of the vaccine strains, in addition to vaccine-induced immune responses at various time points in draining lymph nodes and spleen. We identified sex specific differences in CD8 T cell proliferation in response to mycobacterial antigensex vivo, 90 days post-vaccination, that associates with vaccine mediated protection against HN878. By integrating our multi-parametric datasets into principal component analysis, followed by extraction of high-variance features, we have uncovered an additional significant association of early CD4 T cell responses with late CD8 T cell responses as well as with survival post HN878 infection. In addition, we have also identified specific clusters of responding CD8 T cells in spleen post-vaccination, that are globally deficient in males as compared to females, irrespective of the BCG strain administered.

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“…Tissue processing for flow cytometry staining: Tissue processing and flow cytometry staining were performed as previously described 46 . Briefly, mice were euthanized, and their lungs, spleens, and blood were processed.…”

Section: Confirmation and Sample Collectionmentioning

confidence: 99%

Unveiling the Immune Dynamics of Neisseria Persistent Oral Colonization: A Roadmap for Innovative Vaccine Strategies

Alles,

Gunasena,

Zia

et al. 2023

Preprint

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Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans perspective, but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to Neisseria musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from lung, blood and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria.

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Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c

Cited by 13 publications

References 57 publications

Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection

Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection

Sex differences in vaccine induced immunity and protection againstMycobacterium tuberculosis

Unveiling the Immune Dynamics of Neisseria Persistent Oral Colonization: A Roadmap for Innovative Vaccine Strategies

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