Intranasal Vaccination with rePcrV Protects against Pseudomonas aeruginosa and Generates Lung Tissue-Resident Memory T Cells

Abstract

Tissue-resident memory T (TRM) cells are immune sentinels that bear a key role in the local immune system and rapidly respond to infection. Our previous studies showed that mucosal immunization via intranasal pathways was more effective than intramuscular route. However, the mechanism of enhanced protective immunity remains unclear. Here, we formulated a Pseudomonas aeruginosa vaccine composed of type III secretion protein PcrV from P. aeruginosa and curdlan adjuvant and then administered by the intranasal route. Flow cytometry and immunofluorescence staining showed that the ratio of CD44+CD62L-CD69+CD4+ TRM cells induced by this vaccine was significantly increased, and IL-17A production was notably enhanced. Further analysis revealed that vaccinated mice can protect against the P. aeruginosa challenge even after administration with FTY720 treatment. What is more, our results showed that CD4+ TRM might be involved in the recruitment of neutrophils and provided partial protection against Pseudomonas aeruginosa. Taken together, these data demonstrated that CD4+ TRM cells were elicited in lung tissues after immunization with rePcrV and contributed to protective immunity. Furthermore, it provided novel strategies for the development of vaccines for P. aeruginosa and other respiratory-targeted vaccines.

Progress towards Adjuvant Development: Focus on Antiviral Therapy

“…Curdlan is used in Pseudomonas aeruginosa vaccine and induces the production of high levels of IL-17A and CD44+ CD62L-CD69+ CD4+ TRM cells [158]. Curdlan is also able to activate dendritic cells (DCs) and enhance DC-based antitumor immunity and for this reason is under evaluation for antitumor immunotherapy [159].…”

Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development

“…When proteins of interests are fused with the secretion signal of a T3SS effector ExoS (S 54 ) ( 16 ), and the strain P. aeruginosa was deleted of all its native T3SS effectors while maintaining a functional injectisome, the recombinant proteins can be efficiently injected into various cell lines such as A549, 5637, HL‐60, mESCs and hESCs ( 17 ). Notably, the P. aeruginosa also naturally colonizes in the lungs, conferring a convenient intranasal route to stimulation of tissue-resident immunity ( 18 , 19 ). Hence, due to its excellent delivery ability and possibility of eliciting both CD4 + and CD8 + immune response, we developed a series of T3SS-based aPA vaccines, in which the T3SS effectors, secretion repressor, and several acute virulence factors were deleted, as well as a gene essential for growth to confer the auxotrophic phenotype.…”