Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.

Marinaik, Chandranaik B; Kingstad-Bakke, Brock; Lee, Woojong; Hatta, Masato; Sonsalla, Michelle; Larsen, Autumn; Neldner, Brandon; Gasper, David J et al. · Cell Rep Med · 2020

basic_science · Level V

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Abstract

Induction of protective mucosal T cell memory remains a formidable challenge to vaccinologists. Using a combination adjuvant strategy that elicits potent CD8 and CD4 T cell responses, we define the tenets of vaccine-induced pulmonary T cell immunity. An acrylic-acid-based adjuvant (ADJ), in combination with Toll-like receptor (TLR) agonists glucopyranosyl lipid adjuvant (GLA) or CpG, promotes mucosal imprinting but engages distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of T<sub>H</sub>1/T<sub>C</sub>1/T<sub>H</sub>17/T<sub>C</sub>17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampens T cell receptor (TCR) signaling, mitigates terminal differentiation of effectors, and enhances the development of CD4 and CD8 T<sub>RM</sub> cells that protect against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells play a vital role in optimal programming of CD8 T<sub>RM</sub> and viral control. Taken together, these findings provide further insights into vaccine-induced multifaceted mucosal T cell immunity with implications in the development of vaccines against respiratorypathogens, including influenza virus and SARS-CoV-2.

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