Optimization of a liver Trm cell-inducing mRNA vaccine by reduction of type I interferon response
Minnell, J. J.; Ganley, M.; Lee, A. R.; Phabmixay, T.; Farrand, K. J.; Burn, O. K.; Mamum, J. C.; Lamb, E.; Draper, S. L.; Chan, S. T. S.; Palmer, O. R.; Mason, N. C.; Bilbrough, T.; Anderson, R. J.; Compton, B. J.; Cozijnsen, A.; McKenzie, R. E.; Vink, J. N. A.; Le, S.; Jayasinghe, D.; Gras, S.; McFadden, G. I.; Heath, W. R.; Beattie, L.; Painter, G. F.; Holz, L. E.; Hermans, I. F.
Show abstract
CD8+ tissue-resident memory T cells provide rapid frontline protection at pathogen invasion sites, making them attractive targets for vaccine-mediated immunity. We previously developed an NKT cell-adjuvanted mRNA lipoplex vaccine capable of inducing liver Trm cells and sterile protection against malaria in mice. Here, we show that type I interferon (IFN-I) signalling through dendritic cells -- not T cells -- is a key brake on liver Trm induction by this vaccine. Optimising mRNA manufacturing to reduce immunostimulatory contaminants substantially dampened IFN-I production, boosted antigen expression in the lymphoid tissues, and drove significantly greater Trm accumulation. These enhanced responses translated into superior protection against parasite challenge. Our findings identify DC-intrinsic IFN-I signalling as a tractable target, and mRNA manufacturing quality as a critical and underappreciated lever, for maximising Trm-based vaccine efficacy.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Durability of DNA-LNP and mRNA-LNP Vaccine-Induced Immunity Against SARS-CoV-2 XBB.1.5 97%
- Heterologous immunization modulates B-cell epitope competition between helper peptides and the MPER segment in MPER/liposome vaccines 97%
- An Epitope-based Malaria Vaccine Targeting the Junctional Domain of Circumsporozoite Protein 97%
Similar papers in this journal
- Protective mucosal immunity against SARS-CoV-2 after heterologous systemic RNA-mucosal adenoviral vector immunization 96%
- Ending transmission of SARS-CoV-2: sterilizing immunity using an intranasal subunit vaccine 96%
- Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex 96%
Similar papers in this journal
- MDSC depletion during immunization with heat-killed Mycobacterium tuberculosis increases protection against BCG infection. 95%
- Combination of a Sindbis-SARS-CoV-2 spike vaccine and αOX40 antibody elicits protective immunity against SARS-CoV-2 induced disease and potentiates long-term SARS-CoV-2-specific humoral and T-cell immunity 95%
- Polymeric Pathogen-like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus 95%
Similar papers in this journal
- A Mimicry-Based Strategy Between Human and Commensal Antigens for the Development of a New Family of Immune Therapies for Cancer 95%
- Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma 95%
- Intratumor Childhood Vaccine-Specific CD4+ T cell Recall Coordinates Antitumor CD8+ T cells and Eosinophils 95%
Similar papers in this journal
- A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice 96%
- mRNA-LNP vaccines against Hepatitis B virus induce protective immune responses in preventive and chronic mouse challenge models 95%
- Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.