Harnessing Cross-Reactive CD8<sup>+</sup>T<sub>RM</sub>Cells for Long-Standing Protection Against Influenza A Virus

Uddbäck, Ida; Kohlmeier, Jacob E.; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard

doi:10.1089/vim.2019.0177

Cited by 7 publications

(5 citation statements)

References 62 publications

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“…We observed a marked contraction of the T H 17 response over time after vaccination. This response was associated with impaired vaccine efficacy, and this contraction is similar to the CD8 + T cell responses after influenza infection in the lung ( 48 , 49 ), but lung CD8 + T cell contraction was not observed after recombinant adenovirus vaccination for influenza ( 49 ). We hypothesize that other adjuvants or vaccine platforms may lead to more sustained CD4 + TRM responses, and additional studies on the molecular mechanisms involved in CD4 + T cell contraction may provide insights that guide the development of durable vaccine-induced T cell responses.…”

Section: Discussionmentioning

confidence: 75%

Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

et al. 2021

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Tissue-resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from Klebsiella pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both T H 1 and T H 17 cells that shared transcriptional features with cells elicited by heat-killed K. pneumoniae. Antibody responses were required to prevent bacterial dissemination but dispensable for lung-specific immunity. In contrast, lung immunity required CD4 + T cells, STAT3 expression, and IL-17R signaling in fibroblasts. Lung-specific CD4 + T cells from OmpX+LTA1-immunized mice were observed homing to the lung and could mediate protection against infection in an adoptive transfer model. Vaccine-elicited T H 17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with T H 1 cells, and T H 17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a promising vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae.

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Section: Discussionmentioning

confidence: 75%

Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

et al. 2021

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“…CD8 + T cells recognize viral peptides derived from internal viral components that are less subject to antibody-selected antigenic drift, and therefore more conserved across influenza strains and subtypes (3,4). Indeed, CD8 + T cells specific to conserved viral epitopes correlate with protection against symptomatic influenza illness, making a vaccine capable of stimulating heterologous CD8 + T cells an attractive target in vaccine design (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell-natural killer cell cross-talk modulates T cell activation in response to influenza A viral infection

et al. 2022

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Influenza viruses lead to substantial morbidity and mortality including ~3-5 million cases of severe illness and ~290,000-650,000 deaths annually. One of the major hurdles regarding influenza vaccine efficacy is generating a durable, robust cellular immune response. Appropriate stimulation of the innate immune system is key to generating cellular immunity. Cross-talk between innate dendritic cells (DC) and natural killer (NK) cells plays a key role in activating virus-specific T cells, yet the mechanisms used by influenza A viruses (IAV) to govern this process remain incompletely understood. Here, we used an ex vivo autologous human primary immune cell culture system to evaluate the impact of DC-NK cell cross-talk and subsequent naïve T cell activation at steady-state and after exposure to genetically distinct IAV strains–A/California/07/2009 (H1N1) and A/Victoria/361/2011 (H3N2). Using flow cytometry, we found that exposure of DCs to IAV in co-culture with NK cells led to a decreased frequency of CD83+ and CD86+ cells on DCs and an increased frequency of HLA-DR+ on both DCs and NK cells. We then assessed the outcome of DC-NK cell cross-talk on T cell activation. At steady-state, DC-NK cell cross-talk increased pan T cell CD69 and CD25 expression while exposure to either IAV strain reduced pan T cell CD25 expression and suppressed CD4+ and CD8+ T cell IFN-γ and TNF production, following chemical stimulation with PMA/Ionomycin. Moreover, exposure to A/Victoria/361/2011 elicited lower IFN-γ production by CD4+ and CD8+ T cells compared with A/California/07/2009. Overall, our results indicate a role for DC-NK cell cross-talk in T cell priming in the context of influenza infection, informing the immunological mechanisms that could be manipulated for the next generation of influenza vaccines or immunotherapeutics.

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“…Unlike HA and NA, NP is highly conserved [ 36 ]. Many reports demonstrated that NP-specific T cell responses, including CD4+ and CD8+ T cell responses, contributed to heterosubtypic protection and long-term immune memory [ 37 , 38 , 39 , 40 , 41 ]. Some conserved HLA I and II-recognized epitopes have been characterized.…”

Section: Antigenic Structures Conserved Over Different Influenza Tmentioning

confidence: 99%

Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches

Tang

Zhu

Wang

2020

Viruses

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Influenza is one of the top threats to public health. The best strategy to prevent influenza is vaccination. Because of the antigenic changes in the major surface antigens of influenza viruses, current seasonal influenza vaccines need to be updated every year to match the circulating strains and are suboptimal for protection. Furthermore, seasonal vaccines do not protect against potential influenza pandemics. A universal influenza vaccine will eliminate the threat of both influenza epidemics and pandemics. Due to the massive challenge in realizing influenza vaccine universality, a single vaccine strategy cannot meet the need. A comprehensive approach that integrates advances in immunogen designs, vaccine and adjuvant nanoplatforms, and vaccine delivery and controlled release has the potential to achieve an effective universal influenza vaccine. This review will summarize the advances in the research and development of an affordable universal influenza vaccine.

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Harnessing Cross-Reactive CD8⁺T_RMCells for Long-Standing Protection Against Influenza A Virus

Cited by 7 publications

References 62 publications

Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

Dendritic cell-natural killer cell cross-talk modulates T cell activation in response to influenza A viral infection

Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches

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Harnessing Cross-Reactive CD8+TRMCells for Long-Standing Protection Against Influenza A Virus

Cited by 7 publications

References 62 publications

Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

Dendritic cell-natural killer cell cross-talk modulates T cell activation in response to influenza A viral infection

Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches

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Harnessing Cross-Reactive CD8⁺T_RMCells for Long-Standing Protection Against Influenza A Virus