Manganese‐Based Nanoparticle Vaccine for Combating Fatal Bacterial Pneumonia

Abstract

Bacterial pneumonia is the leading cause of death worldwide among all infectious diseases. However, currently available vaccines against fatal bacterial lung infections, including pneumonic plague, are accompanied by limitations, including insufficient antigen‐adjuvant co‐delivery and inadequate immune stimulation. Therefore, there is an urgent requirement to develop next‐generation vaccines to improve the interaction between antigen and adjuvant, as well as enhance the effects of immune stimulation. Our study developed a novel amino‐decorated mesoporous manganese silicate nanoparticle (AMMSN) loaded with rF1‐V10 (rF1‐V10@AMMSN) to prevent pneumonic plague. Our results suggest that subcutaneous immunization with rF1‐V10@AMMSN in a prime‐boost strategy induces robust production of rF1‐V10‐specific IgG antibodies with a geometric mean titer of 315844 at day 42 post‐primary immunization, which confers complete protection to mice against 50×LD50 of Yersinia pestis (Y. pestis) challenge via the aerosolized intratracheal route. Mechanistically, rF1‐V10@AMMSN can be taken up by dendritic cells (DCs) and promote DCs maturation through activation of the cyclic GMP–AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway and production of type I interferon. This process results in enhanced antigen presentation and promotes rF1‐V10‐mediated protection against Y. pestis infection. This manganese‐based nanoparticle vaccine represents a valuable strategy for combating fatal bacterial pneumonia.This article is protected by copyright. All rights reserved

Zinc–Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy

“…Compared with the other treatment groups, the FZOH + αPD-1 treatment group exhibited significantly greater maturation of DCs (Figure B,C). Mature DCs effectively present antigens and activate T cells . Therefore, the proportions of CD4 + and CD8 + T cells in the FZOH and FZOH + αPD-1 treatment groups increased, especially in the FZOH + αPD-1 group (Figure D,E).…”

“…Mature DCs effectively present antigens and activate T cells. 43 Therefore, the proportions of CD4 + and CD8 + T cells in the FZOH and FZOH + αPD-1 treatment groups increased, especially in the FZOH + αPD-1 group (Figure 7D,E). The release of DAMPs by FZOH-induced immunogenic cell death promoted antigen presentation and stimulated DC maturation.…”

Glycopolypeptide Coordinated Nanovaccine: Fabrication, Characterization, and Antitumor Immune Response

“…27−29 Through the coordination of manganese ions and imidazole groups, scientists have developed a variety of pH-sensitive coordination nanomaterials, which have promising applications in protein delivery and immunotherapy. 30,31 Synthetic polypeptide is one of the candidate materials for drug delivery because of its desirable biocompatibility, biodegradability, and unique secondary conformations, and some polypeptide nanomedicines and hydrogels have entered clinical trials. 32,33 In the antigen delivery and immunotherapy fields, our group previously prepared photoresponsive vesicles by glycosylated polypeptide amphiphiles for antigen delivery, and the glucose-coated polypeptide vesicles effectively delivered antigen into cells and triggered release through UV-irradiation-induced morphology transformation, thus activating a cellular immune response.…”

“…It is believed that manganese ions can increase the sensitivity of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) to double-stranded DNA and promote stimulator of interferon gene (STING) activation, i.e., as an agonist of the cGAS-STING pathway. For example, Jiang et al discovered manganese ions played dual functions of alarmin and agonist in the cGAS-STING pathway, promoting the secretion of type I interferon, then recruiting professional immune cells such as macrophages, dendritic cells, and lymphocytes and promoting the maturation and antigen presentation of dendritic cells, thereby activating immunity. − Through the coordination of manganese ions and imidazole groups, scientists have developed a variety of pH-sensitive coordination nanomaterials, which have promising applications in protein delivery and immunotherapy. , …”