tetano
Editor, Senior Moderator
ACS Appl Mater Interfaces
. 2024 Dec 26.
doi: 10.1021/acsami.4c16246. Online ahead of print. Dual-Engineered Phage Vaccine Platform Facilitates STING Activation for Influenza Protection
Fei Wang[SUP] 1 [/SUP], Shuhan Chen[SUP] 2 [/SUP], Yinhe Xia[SUP] 1 [/SUP], Caihong Liu[SUP] 3 [/SUP], Zhou Xu[SUP] 1 [/SUP], Ruilong Song[SUP] 3 [/SUP], Wenfeng Liu[SUP] 1 [/SUP], Tingting Liu[SUP] 4 [/SUP], Gang Chen[SUP] 1 [/SUP], Qingquan Liu[SUP] 2 [/SUP]
Affiliations
Influenza epidemics remain a global public health challenge. Vaccination with nucleic acid-based vaccines, which trigger strong cellular and humoral immune responses, represents a promising approach for preventing virus infection. However, its effectiveness relies on efficient delivery and an immunoadjuvant. Here, we constructed a gene- and nanoengineered vaccine delivery platform via modifying MnO[SUB]2[/SUB] nanoparticles (NPs) onto the surface of the M13 phage, which carried the hemagglutinin stem gene of influenza A virus preceded by a eukaryotic initial transcriptional region. Specifically, the M13 phage protected the inserted nucleic acid vaccine against degradation due to the existence of capsid proteins. MnO[SUB]2[/SUB] NPs released Mn[SUP]2+[/SUP] ions under the acidic condition of endolysosomes, thereby promoting the cytoplasmic delivery of phage vaccines, which significantly improved the antigen expression. Moreover, Mn[SUP]2+[/SUP] acted as a potent adjuvant for dendritic cell maturation by activating the cGAS/STING pathway. Immunization with the engineered phage vaccine induced CD4[SUP]+[/SUP] T cell, CD8[SUP]+[/SUP] T cell, and humoral immune responses in mice. In infected mouse models, the vaccines ameliorated weight loss, survival rate, lung virus titers, and pulmonary pathologies and conferred full protection against influenza viruses. Collectively, we developed a dual-engineered phage vaccine platform, offering an alternative regimen for optimizing nucleic acid vaccines, which may have broad applications in the rational design of vaccine formulations.
Keywords: MnO2 nanoparticles; STING pathway; influenza virus; phage; vaccine delivery.
. 2024 Dec 26.
doi: 10.1021/acsami.4c16246. Online ahead of print. Dual-Engineered Phage Vaccine Platform Facilitates STING Activation for Influenza Protection
Fei Wang[SUP] 1 [/SUP], Shuhan Chen[SUP] 2 [/SUP], Yinhe Xia[SUP] 1 [/SUP], Caihong Liu[SUP] 3 [/SUP], Zhou Xu[SUP] 1 [/SUP], Ruilong Song[SUP] 3 [/SUP], Wenfeng Liu[SUP] 1 [/SUP], Tingting Liu[SUP] 4 [/SUP], Gang Chen[SUP] 1 [/SUP], Qingquan Liu[SUP] 2 [/SUP]
Affiliations
- PMID: 39723915
- DOI: 10.1021/acsami.4c16246
Influenza epidemics remain a global public health challenge. Vaccination with nucleic acid-based vaccines, which trigger strong cellular and humoral immune responses, represents a promising approach for preventing virus infection. However, its effectiveness relies on efficient delivery and an immunoadjuvant. Here, we constructed a gene- and nanoengineered vaccine delivery platform via modifying MnO[SUB]2[/SUB] nanoparticles (NPs) onto the surface of the M13 phage, which carried the hemagglutinin stem gene of influenza A virus preceded by a eukaryotic initial transcriptional region. Specifically, the M13 phage protected the inserted nucleic acid vaccine against degradation due to the existence of capsid proteins. MnO[SUB]2[/SUB] NPs released Mn[SUP]2+[/SUP] ions under the acidic condition of endolysosomes, thereby promoting the cytoplasmic delivery of phage vaccines, which significantly improved the antigen expression. Moreover, Mn[SUP]2+[/SUP] acted as a potent adjuvant for dendritic cell maturation by activating the cGAS/STING pathway. Immunization with the engineered phage vaccine induced CD4[SUP]+[/SUP] T cell, CD8[SUP]+[/SUP] T cell, and humoral immune responses in mice. In infected mouse models, the vaccines ameliorated weight loss, survival rate, lung virus titers, and pulmonary pathologies and conferred full protection against influenza viruses. Collectively, we developed a dual-engineered phage vaccine platform, offering an alternative regimen for optimizing nucleic acid vaccines, which may have broad applications in the rational design of vaccine formulations.
Keywords: MnO2 nanoparticles; STING pathway; influenza virus; phage; vaccine delivery.