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NPJ Vaccines . Immunization with virus-like vesicle-based COVID-19 vaccine induces robust systemic and mucosal immunity

tetano

Editor, Senior Moderator
NPJ Vaccines


. 2025 Sep 29;10(1):211.
doi: 10.1038/s41541-025-01260-4. Immunization with virus-like vesicle-based COVID-19 vaccine induces robust systemic and mucosal immunity

Lei Yang[SUP] 1 [/SUP], Timur O Yarovinsky[SUP] 1 [/SUP], Kien Pham[SUP] 1 [/SUP], Yibo Xi[SUP] 1 [/SUP], Peiwen Lu[SUP] 2 [/SUP], Akiko Iwasaki[SUP] 2 [/SUP], John K Rose[SUP] 1 [/SUP], Chen Liu[SUP] 3 [/SUP]



Affiliations
Abstract

Coronavirus disease 2019 (COVID-19) has led to significant global morbidity and mortality. Although several vaccines are approved, developing more effective candidates remains essential for long-term prevention. In this study, we present a COVID-19 vaccine candidate using a virus-like vesicle (VLV) platform, an enveloped self-amplifying RNA replicon incorporating an evolved Semliki Forest virus RNA polymerase and VSV glycoprotein. Two constructs were generated: VLV-S-FL (full-length spike protein) and VLV-S-RBD (receptor-binding domain). In C57BL/6J mice, VLV-S-FL elicited robust anti-spike antibody and T cell responses, with antibody levels comparable to those induced by the BNT162b2 mRNA vaccine. Prime-boost immunization with VLV-S-FL provided in vivo protection against SARS-CoV-2. Notably, intranasal boosting enhanced mucosal immunity, including IgA production and recruitment of CD4+ T, CD8+ T, and B cells in BALF. These findings suggest that VLV-S-FL is a promising COVID-19 vaccine capable of inducing both systemic and mucosal immune responses to prevent infection and reduce disease severity.


 
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