Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice

Megan A Files; Kubra F Naqvi; Tais B Saito; Tara M Clover; Jai S Rudra; Janice J Endsley

doi:10.1038/s41541-022-00466-0

Self-adjuvanting nanovaccines boost lung-resident CD4⁺ T cell immune responses in BCG-primed mice

NPJ Vaccines. 2022 Apr 26;7(1):48. doi: 10.1038/s41541-022-00466-0.

Authors

Megan A Files^{1

2}, Kubra F Naqvi³, Tais B Saito^{4

5}, Tara M Clover⁶, Jai S Rudra⁷, Janice J Endsley⁸

Affiliations

¹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
² Institute of Translational Science, University of Texas Medical Branch, Galveston, TX, 77555, USA.
³ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
⁴ Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
⁵ Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
⁶ Comprehensive Industrial Hygiene Laboratory (CIHL), Navy Environmental and Preventive Medicine Unit TWO (NEPMU-2), Department of the Navy, Norfolk, VA, 23551, USA.
⁷ Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA. srudra22@wustl.edu.
⁸ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. jjendsle@utmb.edu.

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.

Abstract

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