New Tuberculosis Vaccine Strategies: Taking Aim at Un-Natural Immunity

Jeyanathan, Mangalakumari; Yao, Yushi; Afkhami, Sam; Smaill, Fiona; Xing, Zhou

doi:10.1016/j.it.2018.01.006

Cited by 59 publications

(93 citation statements)

References 118 publications

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“…The location of these T cells is crucial for the efficacy of the vaccine since the T cells have to be in direct contact with the Mtb infected macrophages [4,5,55]. Therefore, respiratory mucosal vaccination is believed to be the best way to teach the lung macrophages and dendritic cells (DCs) how to fight Mtb infection and to recruit antigen specific T cells to the site of infection (lung parenchyma and airway) [6,58].…”

Section: Discussionmentioning

confidence: 99%

“…These three cell lines were selected to give us an initial broad screen of cell types. In vitro cytotoxicity studies carried out in both nanoparticles and microparticles ( Figure 6) showed no toxic effects on either MH-S, THP-1 or RAW264.7 cells at all concentrations evaluated (6,12,25,50, 100 and 200 µg/mL). In both cases, >75% of cells were viable even at the highest concentration of 200 µg/mL tested.…”

Section: In Vitro Studies In Murine and Human Origin Cell Lines: Cellmentioning

confidence: 97%

“…Overcoming this delay is crucial for the design and development of a successful TB vaccine since this delay allows Mtb bacilli to proliferate in the AMs. Thus, respiratory mucosal vaccines promoting the recruitment of T cells in the lungs in order to control Mtb growth might be a promising strategy against pulmonary TB, as it has been shown to be critical for early infection control [6].Therefore, within this study, we have evaluated an immunisation strategy based on the parenteral priming of a T cell helper (Th) −17 response followed by mucosal boosting using free antigen or aerodynamically engineering particles. The cationic adjuvant formulation (CAF) 01 was selected as the "primer" since it has been previously reported that priming with CAF01 + Antigen facilitates a mixed Th1/Th17 response promoting rapid T cell homing to the lungs after airway boosting [7] and that the administration of CAF01 in combination with H56 TB antigen by parenteral route produces early CD4 T cell responses in the lungs after TB infection [5].…”

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confidence: 99%

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confidence: 99%

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Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting

et al. 2019

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Formulation of inhalable delivery systems containing tuberculosis (TB) antigens to target the site of infection (lungs) have been considered for the development of subunit vaccines. Inert delivery systems such as poly (lactic-co-glycolic acid) (PLGA) are an interesting approach due to its approval for human use. However, PLGA suffers hydrolytic degradation when stored in a liquid environment for prolonged time. Therefore, in this study, nano- and microparticles composed of different PLGA copolymers (50:50, 75:25 and 85:15), sucrose (10% w/v) and L-leucine (1% w/v) encapsulating H56 TB vaccine candidate were produced as dried powders. In vitro studies in three macrophage cell lines (MH-S, RAW264.7 and THP-1) showed the ability of these cells to take up the formulated PLGA:H56 particles and process the antigen. An in vivo prime-pull immunisation approach consisting of priming with CAF01:H56 (2 × subcutaneous (s.c.) injection) followed by a mucosal boost with PLGA:H56 (intranasal (i.n.) administration) demonstrated the retention of the immunogenicity of the antigen encapsulated within the lyophilised PLGA delivery system, although no enhancing effect could be observed compared to the administration of antigen alone as a boost. The work here could provide the foundations for the scale independent manufacture of polymer delivery systems encapsulating antigens for inhalation/aerolisation to the lungs.

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Section: Discussionmentioning

confidence: 99%

Section: In Vitro Studies In Murine and Human Origin Cell Lines: Cellmentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting

et al. 2019

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“…Not only will there be new drugs for TB but also the use of host-directed therapies and newer regimens might allow short treatment durations (Tiberi et al, 2018). There might even be a vaccine available (Jeyanathan et al, 2018). Despite epochal shifts in diagnosis and treatment, one facet would seem eerily familiar to physicians from the 20th century: the prominence of undernutrition as a driver of the TB pandemic.…”

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confidence: 99%

Crystal ball: the yesterday and tomorrow of tuberculosis

Sinha

Hochberg

2018

Environ Microbiol Rep

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Engineering Vaccines for Tissue‐Resident Memory T Cells

Knight

Wilson

2021

Advanced Therapeutics

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In recent years, tissue‐resident memory T cells (TRM) have attracted significant attention in the field of vaccine development. Distinct from central and effector memory T cells, TRM cells take up residence in home tissues such as the lung or urogenital tract and are ideally positioned to respond quickly to pathogen encounter. TRM are found to play a role in the immune response against many globally important infectious diseases for which new or improved vaccines are needed, including influenza and tuberculosis. It is also increasingly clear that TRM play a pivotal role in cancer immunity. Thus, vaccines that can generate this memory T cell population are highly desirable. The field of immunoengineering—that is, the application of engineering principles to study the immune system and design new and improved therapies that harness or modulate immune responses—is ideally poised to provide solutions to this need for next‐generation TRM vaccines. This review covers recent developments in vaccine technologies for generating TRM and protecting against infection and cancer, including viral vectors, virus‐like particles, and synthetic and natural biomaterials. In addition, it offers critical insights on the future of engineering vaccines for tissue‐resident memory T cells.

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New Tuberculosis Vaccine Strategies: Taking Aim at Un-Natural Immunity

Cited by 59 publications

References 118 publications

Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting

Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting

Crystal ball: the yesterday and tomorrow of tuberculosis

Engineering Vaccines for Tissue‐Resident Memory T Cells

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