Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells.

Autor:	Morgun E; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States., Zhu J; Department of Biomedical Engineering, Northwestern University, Evanston, United States., Almunif S; Department of Biomedical Engineering, Northwestern University, Evanston, United States., Bobbala S; Department of Biomedical Engineering, Northwestern University, Evanston, United States., Aguilar MS; Department of Medicine, University of Washington School of Medicine, Seattle, United States., Wang J; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States., Conner K; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States., Cui Y; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States., Cao L; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States., Seshadri C; Department of Medicine, University of Washington School of Medicine, Seattle, United States., Scott EA; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States., Wang CR; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Oct 25; Vol. 12. Date of Electronic Publication: 2023 Oct 25.
DOI:	10.7554/eLife.87431
Abstrakt:	Mycobacterium tuberculosis (Mtb) infection elicits both protein and lipid antigen-specific T cell responses. However, the incorporation of lipid antigens into subunit vaccine strategies and formulations has been underexplored, and the characteristics of vaccine-induced Mtb lipid-specific memory T cells have remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to unconventional T cell subsets. These MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting that MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized the enhanced stability of bicontinuous nanospheres (BCN) to efficiently encapsulate MA for in vivo delivery to MA-specific T cells, both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary administration of MA-loaded BCN (MA-BCN) elicited MA-specific T cell responses in humanized CD1 transgenic mice. Simultaneous delivery of MA and Ag85B within BCN activated both MA- and Ag85B-specific T cells. Notably, pulmonary vaccination with MA-Ag85B-BCN resulted in the persistence of MA, but not Ag85B, within alveolar macrophages in the lung. Vaccination of MA-BCN through intravenous or subcutaneous route, or with attenuated Mtb likewise reproduced MA persistence. Moreover, MA-specific T cells in MA-BCN-vaccinated mice differentiated into a T follicular helper-like phenotype. Overall, the BCN platform allows for the dual encapsulation and in vivo activation of lipid and protein antigen-specific T cells and leads to persistent lipid depots that could offer long-lasting immune responses. Competing Interests: EM, JZ, SA, SB, MA, JW, KC, YC, LC, CS, ES No competing interests declared, CW Reviewing Editor eLife (© 2023, Morgun et al.)
Databáze:	MEDLINE
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