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Mycolic acid nanoparticle vaccination leads to lipid antigen persistence and unique differentiation of mycobacterial-specific T cells

ABSTRACT: 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 properties of vaccine-induced Mtb lipid-specific memory T cells remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to T cells. MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized bicontinuous nanospheres (BCN) to efficiently encapsulate MA and deliver it to MA-specific T cells both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary delivery 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. Interestingly, pulmonary vaccination with MA-Ag85B-BCN led to 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 to have a T follicular helper-like phenotype. Overall, BCN platform allows for the dual encapsulation of lipid and protein antigen and leads to persistent lipid depots that could offer long-lasting immune response and protection.

ORGANISM(S): Mus musculus

PROVIDER: GSE226075 | GEO | 2023/04/25

REPOSITORIES: GEO

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