tetano
Editor, Senior Moderator
Acta Pharm Sin B
. 2026 Mar;16(3):1625-1642.
doi: 10.1016/j.apsb.2025.12.021. Epub 2026 Jan 5.
Liposomal simvastatin potentiates intranasal H1N1 influenza subunit vaccine via increasing transcytosis of antigen and submucosal dendritic cell recruitment
Afeng Yang[SUP] 1 [/SUP], Chen Zhang[SUP] 1 [/SUP], Aihua Wu[SUP] 1 [/SUP], Jiaojiao Xu[SUP] 1 [/SUP], Hongzheng Lin[SUP] 1 [/SUP], Zhe Li[SUP] 1 [/SUP], Tingting Li[SUP] 1 [/SUP], Yunlu Li[SUP] 1 [/SUP], Ningshao Xia[SUP] 2 [/SUP], Xunlong Shi[SUP] 1 [/SUP], Tianying Zhang[SUP] 2 [/SUP], Wei Lu[SUP] 1 [/SUP]
Affiliations
Intranasal vaccines specifically eliciting mucosal immunity in the upper respiratory tract have shown advantages in protecting against respiratory virus invasion. Yet, no clinically licensed intranasal adjuvant remains a major hurdle for the development of intranasal vaccines with low immunogenic antigens like subunit vaccines. Here, we show that liposomes loading simvastatin (Lipo-SV) serve as potent mucosal adjuvants for the intranasal liposomal subunit vaccine encapsulating the hemagglutinin 1 (HA1) glycoprotein of A/PR/8/34 (PR8) H1N1 influenza (Lipo-HA1), providing robust protection against the lethal PR8 H1N1 infection. Compared to cholera toxin subunit B (CTB), the only mucosal adjuvant used in humans, the Lipo-SV substantiate intranasal Lipo-HA1 vaccines to elicit robust systemic and local mucosal immune responses. The underlying mechanism of the adjuvanticity of Lipo-SV involves the increased transcytosis of antigens by inhibiting the geranylgeranylation of RAB5 and RAB7B GTPases in nasal epithelial cells. Moreover, Lipo-SV enhance the submucosal recruitment of dendritic cell for antigen uptake via the Toll-like receptor 4-dependent pathway. Unlike CTB, intranasal Lipo-SV do not induce inflammation in the lung or the inflammatory cytokines in the central nervous system. Our results present a paradigm of design of mucosal adjuvant to target the mucosal epithelial cells in addition to the antigen-presenting cells.
Keywords: Dendritic cell recruitment; H1N1 influenza; Intranasal adjuvant; Liposomes; Nasal epithelial cells; Simvastatin; Subunit vaccine; Transcytosis of antigens.
. 2026 Mar;16(3):1625-1642.
doi: 10.1016/j.apsb.2025.12.021. Epub 2026 Jan 5.
Liposomal simvastatin potentiates intranasal H1N1 influenza subunit vaccine via increasing transcytosis of antigen and submucosal dendritic cell recruitment
Afeng Yang[SUP] 1 [/SUP], Chen Zhang[SUP] 1 [/SUP], Aihua Wu[SUP] 1 [/SUP], Jiaojiao Xu[SUP] 1 [/SUP], Hongzheng Lin[SUP] 1 [/SUP], Zhe Li[SUP] 1 [/SUP], Tingting Li[SUP] 1 [/SUP], Yunlu Li[SUP] 1 [/SUP], Ningshao Xia[SUP] 2 [/SUP], Xunlong Shi[SUP] 1 [/SUP], Tianying Zhang[SUP] 2 [/SUP], Wei Lu[SUP] 1 [/SUP]
Affiliations
- PMID: 41909735
- PMCID: PMC13031069
- DOI: 10.1016/j.apsb.2025.12.021
Intranasal vaccines specifically eliciting mucosal immunity in the upper respiratory tract have shown advantages in protecting against respiratory virus invasion. Yet, no clinically licensed intranasal adjuvant remains a major hurdle for the development of intranasal vaccines with low immunogenic antigens like subunit vaccines. Here, we show that liposomes loading simvastatin (Lipo-SV) serve as potent mucosal adjuvants for the intranasal liposomal subunit vaccine encapsulating the hemagglutinin 1 (HA1) glycoprotein of A/PR/8/34 (PR8) H1N1 influenza (Lipo-HA1), providing robust protection against the lethal PR8 H1N1 infection. Compared to cholera toxin subunit B (CTB), the only mucosal adjuvant used in humans, the Lipo-SV substantiate intranasal Lipo-HA1 vaccines to elicit robust systemic and local mucosal immune responses. The underlying mechanism of the adjuvanticity of Lipo-SV involves the increased transcytosis of antigens by inhibiting the geranylgeranylation of RAB5 and RAB7B GTPases in nasal epithelial cells. Moreover, Lipo-SV enhance the submucosal recruitment of dendritic cell for antigen uptake via the Toll-like receptor 4-dependent pathway. Unlike CTB, intranasal Lipo-SV do not induce inflammation in the lung or the inflammatory cytokines in the central nervous system. Our results present a paradigm of design of mucosal adjuvant to target the mucosal epithelial cells in addition to the antigen-presenting cells.
Keywords: Dendritic cell recruitment; H1N1 influenza; Intranasal adjuvant; Liposomes; Nasal epithelial cells; Simvastatin; Subunit vaccine; Transcytosis of antigens.