Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants

Marinaik, Chandranaik B.; Kingstad-Bakke, Brock; Lee, Woo‐Jong; Hatta, Masato; Sonsalla, Michelle; Larsen, Autumn; Neldner, Brandon; Gasper, David J.; Kedl, Ross M.; Kawaoka, Yoshihiro; Suresh, M.

doi:10.1101/2020.07.10.197459

Cited by 2 publications

(2 citation statements)

References 59 publications

(69 reference statements)

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“…In vaccine studies in the lung against influenza viruses, adjuvants, which are TLR agonist, induce an effective polyfunctional T cell immunity. Nevertheless, the induction of CD69 and CD103 expression was similar between different adjuvants [ 80 ]. A direct activation and differentiation of T RM cells by TLR activation could not be shown in the liver yet.…”

Section: Liver T Rm Cells—in Health Disease Anmentioning

confidence: 99%

Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists

Bartsch

Damasio

Subudhi

et al. 2020

Cells

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T cells play an important role to build up an effective immune response and are essential in the eradication of pathogens. To establish a long-lasting protection even after a re-challenge with the same pathogen, some T cells differentiate into memory T cells. Recently, a certain subpopulation of memory T cells at different tissue-sites of infection was detected—tissue-resident memory T cells (TRM cells). These cells can patrol in the tissue in order to encounter their cognate antigen to establish an effective protection against secondary infection. The liver as an immunogenic organ is exposed to a variety of pathogens entering the liver through the systemic blood circulation or via the portal vein from the gut. It could be shown that intrahepatic TRM cells can reside within the liver tissue for several years. Interestingly, hepatic TRM cell differentiation requires a distinct cytokine milieu. In addition, TRM cells express specific surface markers and transcription factors, which allow their identification delimited from their circulating counterparts. It could be demonstrated that liver TRM cells play a particular role in many liver diseases such as hepatitis B and C infection, non-alcoholic fatty liver disease and even play a role in the development of hepatocellular carcinoma and in building long-lasting immune responses after vaccination. A better understanding of intrahepatic TRM cells is critical to understand the pathophysiology of many liver diseases and to identify new potential drug targets for the development of novel treatment strategies.

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Section: Liver T Rm Cells—in Health Disease Anmentioning

confidence: 99%

Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists

Bartsch

Damasio

Subudhi

et al. 2020

Cells

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show abstract

“…Carbomer-based adjuvants have shown great promise in veterinary vaccines (22,23), in stimulating neutralizing antibodies against HIV and malaria antigens (24,25), and also in experimental vaccines against influenza virus in mice (26)(27)(28)(29). Combination adjuvants provide effective T cell-based immunity to influenza A virus (29), but is unknown whether vaccines formulated in ADJ can provide T-cell-based protection against systemic infections.…”

Section: Introductionmentioning

confidence: 99%

Subunit Vaccine-Elicited Effector-Like Memory CD8 T Cells Protect Against Listeriosis

Lee

Larsen

Kingstad-Bakke

et al. 2020

Preprint

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Development of T-cell-based subunit protein vaccines against diseases, such as AIDS, tuberculosis and malaria remains a challenge for immunologists. Here, we have evaluated whether cross-presentation induced by nanoemulsion adjuvant Adjuplex (ADJ), can be combined with the immunomodulatory effects of TLR agonists (CpG or glucopyranosyl lipid adjuvant [GLA]) to evoke protective systemic CD8 T cell-based immunity to Listeria monocytogenes (LM). Vaccination with ADJ, alone or in combination with CpG or GLA augmented activation and antigen uptake by migratory and resident dendritic cells and up-regulated CD69 expression on B and T lymphocytes in draining lymph nodes. By virtue of its ability to engage BATF3-dependent cross-presenting DCs, ADJ potently elicited effector CD8 T cells that differentiated into a distinct subset of granzyme B-expressing CD27LO effector-like memory CD8 T cells, which provided highly effective immunity to LM in spleen and liver. CpG or GLA alone did not elicit effector-like memory CD8 T cells and induced moderate protection in spleen, but not in the liver. Surprisingly, combining CpG or GLA with ADJ limited the magnitude of ADJ-induced CD8 T cell memory and compromised protective immunity to LM, especially in the liver. Taken together, data presented in this manuscript provides a glimpse of protective CD8 T cell memory differentiation induced by a nano-emulsion adjuvant and demonstrates the unexpected negative effects of TLR signaling on the magnitude of CD8 T cell memory and protective immunity to listeriosis.

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Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants

Cited by 2 publications

References 59 publications

Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists

Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists

Subunit Vaccine-Elicited Effector-Like Memory CD8 T Cells Protect Against Listeriosis

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