@article{2d690d0f0c1c4eaab6a68fee79e7823f,
title = "Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice",
abstract = "Heterologous vaccine regimens could extend waning protection in the global population immunized with Mycobacterium bovis Bacille Calmette-Guerin (BCG). We demonstrate that pulmonary delivery of peptide nanofibers (PNFs) bearing an Ag85B CD4+ T cell epitope increased the frequency of antigen-specific T cells in BCG-primed mice, including heterogenous populations with tissue resident memory (Trm) and effector memory (Tem) phenotype, and functional cytokine recall. Adoptive transfer of dendritic cells pulsed with Ag85B-bearing PNFs further expanded the frequency and functional repertoire of memory CD4+ T cells. Transcriptomic analysis suggested that the adjuvanticity of peptide nanofibers is, in part, due to the release of damage-associated molecular patterns. A single boost with monovalent Ag85B PNF in BCG-primed mice did not reduce lung bacterial burden compared to BCG alone following aerosol Mtb challenge. These findings support the need for novel BCG booster strategies that activate pools of Trm cells with potentially diverse localization, trafficking, and immune function.",
author = "Files, {Megan A.} and Naqvi, {Kubra F.} and Saito, {Tais B.} and Clover, {Tara M.} and Rudra, {Jai S.} and Endsley, {Janice J.}",
note = "Funding Information: Support for Megan Files and Kubra Naqvi was generously provided through pre-doctoral fellowships from the Sealy Institute for Vaccine Sciences, and the James W. McLaughlin Endowment, respectively, at the University of Texas Medical Branch, Galveston, Texas. Research funding was provided through the Washington University McKelvey School of Engineering, Department of Biomedical Engineering Commitment Funds (12–360–94361 J) and the National Institute of Health, National Institute of Allergy and Infectious Diseases (R01 AI130278–01A1) to Dr. Jai Rudra. Drs. Rudra and Endsley were also jointly supported through National Institute of Health, National Institute of Allergy and Infectious Diseases (R21AI115302). The authors would like to thank Mark Griffin and Dr. Yuejin Liang from UTMB{\textquoteright}s flow cytometry core for their guidance with all flow cytometry experiments. We additionally extend gratitude to Dr. William Lawrence and Jennifer Peel in the UTMB Aerobiology Core Facility for performance of Mtb aerosol challenge experiments. The authors further wish to thank Jeffrey Marek for assistance with RNA sequencing analysis, and Dr. Preeti Bharaj for her assistance in formulating flow cytometry panels. Finally, the authors thank the Animal Resource Care team at UTMB for all experimental animal husbandry and care. Funding Information: Support for Megan Files and Kubra Naqvi was generously provided through pre-doctoral fellowships from the Sealy Institute for Vaccine Sciences, and the James W. McLaughlin Endowment, respectively, at the University of Texas Medical Branch, Galveston, Texas. Research funding was provided through the Washington University McKelvey School of Engineering, Department of Biomedical Engineering Commitment Funds (12?360?94361?J) and the National Institute of Health, National Institute of Allergy and Infectious Diseases (R01 AI130278?01A1) to Dr. Jai Rudra. Drs. Rudra and Endsley were also jointly supported through National Institute of Health, National Institute of Allergy and Infectious Diseases (R21AI115302). The authors would like to thank Mark Griffin and Dr. Yuejin Liang from UTMB?s flow cytometry core for their guidance with all flow cytometry experiments. We additionally extend gratitude to Dr. William Lawrence and Jennifer Peel in the UTMB Aerobiology Core Facility for performance of Mtb aerosol challenge experiments. The authors further wish to thank Jeffrey Marek for assistance with RNA sequencing analysis, and Dr. Preeti Bharaj for her assistance in formulating flow cytometry panels. Finally, the authors thank the Animal Resource Care team at UTMB for all experimental animal husbandry and care. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41541-022-00466-0",
language = "English",
volume = "7",
journal = "npj Vaccines",
issn = "2059-0105",
number = "1",
}