Intranasal administration of a virus like particles-based vaccine induces neutralizing antibodies against SARS-CoV-2 and variants of concern

鼻腔内注射病毒样颗粒疫苗可诱导产生针对 SARS-CoV-2 及其相关变体的中和抗体

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作者:Dominik A Rothen, Pascal S Krenger, Aleksandra Nonic, Ina Balke, Anne-Cathrine S Vogt, Xinyue Chang, Alessandro Manenti, Fabio Vedovi, Gunta Resevica, Senta M Walton, Andris Zeltins, Emanuele Montomoli, Monique Vogel, Martin F Bachmann, Mona O Mohsen

Background

The highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of a vaccine against COVID-19.

Conclusion

Our data demonstrate that intranasal administration of CuMVTT -RBD induces a protective systemic and local specific antibody response against SARS-CoV-2 and its VOCs.

Methods

In the current study, we evaluated the immunogenicity of a traditional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal administration in a murine model. The candidate vaccine platform, CuMVTT -RBD, has been optimized to incorporate a universal T helper cell epitope derived from tetanus-toxin and is self-adjuvanted with TLR7/8 ligands.

Results

CuMVTT -RBD vaccine elicited a strong systemic RBD- and spike-IgG and IgA antibodies of high avidity. Local immune response was assessed, and our results demonstrate a strong mucosal antibody and plasma cell production in lung tissue. Furthermore, the induced systemic antibodies could efficiently recognize and neutralize different variants of concern (VOCs).

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