Robust induction of TRMs by combinatorial nanoshells confers cross-strain sterilizing immunity against lethal influenza viruses

Lin, Pin Hung; Liang, Chieh-Yu; Yao, Bing; Chen, Hui-Wen; Pan, Ching Fu; Wu, Liwei; Lin, Yi; Hsu, Yu Sung; Liu, Yu Han; Chen, Pei‐Jer; Hu, Che Ming Jack; Yang, Hung‐Chih

doi:10.1016/j.omtm.2021.03.010

Cited by 7 publications

(1 citation statement)

References 61 publications

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“…Notwithstanding the virtues of the subunit vaccine described herein, one limitation of this study is the response elicited by purified rOVA-3 which is in part attributable to co-purifying endotoxins. Nonetheless, as MPLA is an FDA-approved adjuvant 104,105 , results reported herein are useful for the development of subunit vaccines deliverable via the intranasal route-e.g., FluMist, nasal sprays of quadrivalent, live attenuated influenza viruses, by leveraging advances in delivery platforms and technologies [106][107][108] .…”

Section: Subunit Vaccination-induced Cd8 + Trm Cells Express Lineage-...mentioning

confidence: 99%

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Suryadevara

Kumar

Xiang

et al. 2022

Sci Rep

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Natural infection as well as vaccination with live or attenuated viruses elicit tissue resident, CD8+ memory T cell (Trm) response. Trm cells so elicited act quickly upon reencounter with the priming agent to protect the host. These Trm cells express a unique molecular signature driven by the master regulators—Runx3 and Hobit. We previously reported that intranasal instillation of a subunit vaccine in a prime boost vaccination regimen installed quick-acting, CD8+ Trm cells in the lungs that protected against lethal vaccinia virus challenge. It remains unexplored whether CD8+ Trm responses so elicited are driven by a similar molecular signature as those elicited by microbes in a real infection or by live, attenuated pathogens in conventional vaccination. We found that distinct molecular signatures distinguished subunit vaccine-elicited lung interstitial CD8+ Trm cells from subunit vaccine-elicited CD8+ effector memory and splenic memory T cells. Nonetheless, the transcriptome signature of subunit vaccine elicited CD8+ Trm resembled those elicited by virus infection or vaccination. Clues to the basis of tissue residence and function of vaccine specific CD8+ Trm cells were found in transcripts that code for chemokines and chemokine receptors, purinergic receptors, and adhesins when compared to CD8+ effector and splenic memory T cells. Our findings inform the utility of protein-based subunit vaccination for installing CD8+ Trm cells in the lungs to protect against respiratory infectious diseases that plague humankind.

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Section: Subunit Vaccination-induced Cd8 + Trm Cells Express Lineage-...mentioning

confidence: 99%

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Suryadevara

Kumar

Xiang

et al. 2022

Sci Rep

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Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus

Liu,

Kabir,

Chen

et al. 2024

Adv Healthcare Materials

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Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, we have bioengineered biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366, a nucleoprotein‐derived epitope and PA224, a polymerase acidic subunit derived epitope. These BP‐NP366/PA224 could be manufactured at high yield and are obtained at ∼93% purity exhibiting ambient‐temperature stability. Immunological characterisation includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunisation. Immunization with BP‐NP366/PA224 without adjuvant triggers influenza‐specific CD8+ T cell priming and memory CD8+ T cell development. Co‐delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza‐specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP‐NP366/PA224 with poly(I:C) provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.This article is protected by copyright. All rights reserved

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Lymph Node Follicle‐Targeting STING Agonist Nanoshells Enable Single‐Shot M2e Vaccination for Broad and Durable Influenza Protection

et al. 2023

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The highly conserved matrix protein 2 ectodomain (M2e) of influenza viruses presents a compelling vaccine antigen candidate for stemming the pandemic threat of the mutation-prone pathogen, yet the low immunogenicity of the diminutive M2e peptide renders vaccine development challenging. A highly potent M2e nanoshell vaccine that confers broad and durable influenza protectivity under a single vaccination is shown. Prepared via asymmetric ionic stabilization for nanoscopic curvature formation, polymeric nanoshells co-encapsulating high densities of M2e peptides and stimulator of interferon genes (STING) agonists are prepared. Robust and long-lasting protectivity against heterotypic influenza viruses is achieved with a single administration of the M2e nanoshells in mice. Mechanistically, molecular adjuvancy by the STING agonist and nanoshell-mediated prolongation of M2e antigen exposure in the lymph node follicles synergistically contribute to the heightened anti-M2e humoral responses. STING agonist-triggered T cell helper functions and extended residence of M2e peptides in the follicular dendritic cell network provide a favorable microenvironment that induces Th1-biased antibody production against the diminutive antigen. These findings highlight a versatile nanoparticulate design that leverages innate immune pathways for enhancing the immunogenicity of weak immunogens. The single-shot nanovaccine further provides a translationally viable platform for pandemic preparedness.

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Robust induction of TRMs by combinatorial nanoshells confers cross-strain sterilizing immunity against lethal influenza viruses

Cited by 7 publications

References 61 publications

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus

Lymph Node Follicle‐Targeting STING Agonist Nanoshells Enable Single‐Shot M2e Vaccination for Broad and Durable Influenza Protection

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