tetano
Editor, Senior Moderator
J Nanobiotechnology
. 2023 Dec 13;21(1):479.
doi: 10.1186/s12951-023-02229-y. A novel "prime and pull" strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge
Zhannan Wang[SUP] 1 [/SUP], Yingkai He[SUP] 1 [/SUP], Wenfeng Wang[SUP] 1 [/SUP], Yawen Tian[SUP] 1 [/SUP], Chongbo Ge[SUP] 1 [/SUP], Futing Jia[SUP] 1 [/SUP], Tongyu Zhang[SUP] 1 [/SUP], Gerui Zhang[SUP] 1 [/SUP], Mingyue Wang[SUP] 1 [/SUP], Jinshuo Gong[SUP] 1 [/SUP], Haibin Huang[SUP] 1 [/SUP], Jianzhong Wang[SUP] 1 [/SUP], Chunwei Shi[SUP] 1 [/SUP], Wentao Yang[SUP] 1 [/SUP], Xin Cao[SUP] 1 [/SUP], Yan Zeng[SUP] 1 [/SUP], Nan Wang[SUP] 1 [/SUP], Aidong Qian[SUP] 1 [/SUP], Yanlong Jiang[SUP] 2 [/SUP], Guilian Yang[SUP] 3 [/SUP], Chunfeng Wang[SUP] 4 [/SUP]
Affiliations
Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (T[SUB]RM[/SUB]), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (T[SUB]EM[/SUB]). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b[SUP]+[/SUP] DCs, increased intracellular IL-17 production in lung CD4[SUP]+[/SUP] T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung T[SUB]RM[/SUB]s, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel "prime and pull" strategy for addressing the production of protective T[SUB]RM[/SUB] cells in vaccine design.
Keywords: DC targeting; Influenza virus; Nanoparticle vaccine; Sequential immunization; TRM cell.
. 2023 Dec 13;21(1):479.
doi: 10.1186/s12951-023-02229-y. A novel "prime and pull" strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge
Zhannan Wang[SUP] 1 [/SUP], Yingkai He[SUP] 1 [/SUP], Wenfeng Wang[SUP] 1 [/SUP], Yawen Tian[SUP] 1 [/SUP], Chongbo Ge[SUP] 1 [/SUP], Futing Jia[SUP] 1 [/SUP], Tongyu Zhang[SUP] 1 [/SUP], Gerui Zhang[SUP] 1 [/SUP], Mingyue Wang[SUP] 1 [/SUP], Jinshuo Gong[SUP] 1 [/SUP], Haibin Huang[SUP] 1 [/SUP], Jianzhong Wang[SUP] 1 [/SUP], Chunwei Shi[SUP] 1 [/SUP], Wentao Yang[SUP] 1 [/SUP], Xin Cao[SUP] 1 [/SUP], Yan Zeng[SUP] 1 [/SUP], Nan Wang[SUP] 1 [/SUP], Aidong Qian[SUP] 1 [/SUP], Yanlong Jiang[SUP] 2 [/SUP], Guilian Yang[SUP] 3 [/SUP], Chunfeng Wang[SUP] 4 [/SUP]
Affiliations
- PMID: 38093320
- PMCID: PMC10717309
- DOI: 10.1186/s12951-023-02229-y
Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (T[SUB]RM[/SUB]), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (T[SUB]EM[/SUB]). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b[SUP]+[/SUP] DCs, increased intracellular IL-17 production in lung CD4[SUP]+[/SUP] T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung T[SUB]RM[/SUB]s, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel "prime and pull" strategy for addressing the production of protective T[SUB]RM[/SUB] cells in vaccine design.
Keywords: DC targeting; Influenza virus; Nanoparticle vaccine; Sequential immunization; TRM cell.