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:10.1016/j.xcrm.2020.100095

Cited by 23 publications

(29 citation statements)

References 56 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For indicated studies, vascular staining of T-cells was performed by IV injection of fluorochrome-labeled CD45.2 3 min prior to animal euthanasia. Single-cell suspensions from spleen and lung were prepared using standard techniques as described ( 17 ). Bronchoalveolar lavage (BAL) cells were collected from euthanized mice by cannulating the trachea and flushing 3 times with 1 ml cold 10% FBS-RPMI, followed by cell pelleting.…”

Section: Methodsmentioning

confidence: 99%

“…Several groups have developed vaccines to elicit influenza-specific lung T RM cells that confer heterosubtypic protection to influenza virus challenge using live attenuated influenza viruses ( 13 ), or viral vectors ( 14 ). Recently, we have tested a novel adjuvant, Adjuplex (ADJ, a nano emulsion of carbomer and soy lethicin ( 15 )), that when combined with subunit or IIV proteins potently induced CD8+ lung T RM cell responses after mucosal administration, and conferred substantial protection to influenza virus challenge ( 16 , 17 ). These studies highlight the importance for identification of novel adjuvants that can elicit mucosal CMI to non-replicating antigens, particularly so we can dissect and study the individual effects these adjuvants have on the magnitude and nature of the resultant mucosal CMI responses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus

et al. 2021

Self Cite

View full text Add to dashboard Cite

Eliciting durable and protective T cell-mediated immunity in the respiratory mucosa remains a significant challenge. Polylactic-co-glycolic acid (PLGA)-based cationic pathogen-like particles (PLPs) loaded with TLR agonists mimic biophysical properties of microbes and hence, simulate pathogen-pattern recognition receptor interactions to safely and effectively stimulate innate immune responses. We generated micro particle PLPs loaded with TLR4 (glucopyranosyl lipid adjuvant, GLA) or TLR9 (CpG) agonists, and formulated them with and without a mucosal delivery enhancing carbomer-based nanoemulsion adjuvant (ADJ). These adjuvants delivered intranasally to mice elicited high numbers of influenza nucleoprotein (NP)-specific CD8+ and CD4+ effector and tissue-resident memory T cells (TRMs) in lungs and airways. PLPs delivering TLR4 versus TLR9 agonists drove phenotypically and functionally distinct populations of effector and memory T cells. While PLPs loaded with CpG or GLA provided immunity, combining the adjuvanticity of PLP-GLA and ADJ markedly enhanced the development of airway and lung TRMs and CD4 and CD8 T cell-dependent immunity to influenza virus. Further, balanced CD8 (Tc1/Tc17) and CD4 (Th1/Th17) recall responses were linked to effective influenza virus control. These studies provide mechanistic insights into vaccine-induced pulmonary T cell immunity and pave the way for the development of a universal influenza and SARS-CoV-2 vaccines.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…To reiterate, intranasal (IN) vaccination with a subunit protein formulated with a combination adjuvant (Adjuplex [ADJ] + TLR4 agonist glucopyranosyl lipid A [GLA]) elicited high numbers of TRM CD8 T cells and provided robust protection against IAV (40).…”

Section: Dynamics Of Antigen-processing Innate Immune Cells In Lungs mentioning

confidence: 99%

CCR2 Regulates Vaccine-Induced Mucosal T-Cell Memory to Influenza A Virus

Lee

Kingstad-Bakke

Kedl³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T-cell based vaccines against respiratory viral pathogens such as influenza A virus (IAV). Chemokine receptor 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs, to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendrtitic cells (DCs) and monocyte-derived DCs internalized and processed vaccine antigen in lungs. We also found that Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF-3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127HI/KLRG-1LO, OX40+veCD62L+ve and mucosally imprinted CD69+veCD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs, induced by CCR2 deficiency was linked to dampened expression of T-bet, but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens including IAV and SARS-CoV-2.

show abstract

“…BCG may therefore be considered the first T cell-inducing vaccine, and still the only licensed vaccine promoting primarily T cell responses. In recent years, T cell-inducing vaccines have been evaluated for HIV, influenza, and malaria [ 37 , 68 , 71 , 72 , 73 , 74 , 75 ]. For example, a modified vaccinia virus Ankara (MVA) vector encoding the influenza nucleoprotein and matrix protein 1 (MVA-NP+M1) was tested in human clinical trials and showed a strong Th1 (IFN-γ) response with an acceptable safety profile [ 76 ].…”

Section: Novel Vaccination Approaches Against Respiratory Viral Inmentioning

confidence: 99%

Harnessing Cellular Immunity for Vaccination against Respiratory Viruses

Lukacs

Malinczak

2020

Vaccines

View full text Add to dashboard Cite

Severe respiratory viral infections, such as influenza, metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus (RV), and coronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cause significant mortality and morbidity worldwide. These viruses have been identified as important causative agents of acute respiratory disease in infants, the elderly, and immunocompromised individuals. Clinical signs of infection range from mild upper respiratory illness to more serious lower respiratory illness, including bronchiolitis and pneumonia. Additionally, these illnesses can have long-lasting impact on patient health well beyond resolution of the viral infection. Aside from influenza, there are currently no licensed vaccines against these viruses. However, several research groups have tested various vaccine candidates, including those that utilize attenuated virus, virus-like particles (VLPs), protein subunits, and nanoparticles, as well as recent RNA vaccines, with several of these approaches showing promise. Historically, vaccine candidates have advanced, dependent upon the ability to activate the humoral immune response, specifically leading to strong B cell responses and neutralizing antibody production. More recently, it has been recognized that the cellular immune response is also critical in proper resolution of viral infection and protection against detrimental immunopathology associated with severe disease and therefore, must also be considered when analyzing the efficacy and safety of vaccine candidates. These candidates would ideally result in robust CD4+ and CD8+ T cell responses as well as high-affinity neutralizing antibody. This review will aim to summarize established and new approaches that are being examined to harness the cellular immune response during respiratory viral vaccination.

show abstract

Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants

Cited by 23 publications

References 56 publications

Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus

Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus

CCR2 Regulates Vaccine-Induced Mucosal T-Cell Memory to Influenza A Virus

Harnessing Cellular Immunity for Vaccination against Respiratory Viruses

Contact Info

Product

Resources

About