【摘 要】
：
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global crisis,urgently necessitating the development of safe,efficacious,convenient-to-store,and low-cost vaccine options.A major challenge is that the receptor-binding domain(RBD)-on
【机 构】
：
Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing
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Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global crisis,urgently necessitating the development of safe,efficacious,convenient-to-store,and low-cost vaccine options.A major challenge is that the receptor-binding domain(RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination.To enhance antigen processing and cross-presentation in draining lymph nodes(DLNs),we developed an interferon(IFN)-armed RBD dimerized by an immunoglobulin fragment(I-R-F).I-R-F efficiently directs immunity against RBD to DLNs.A low dose of l-R-F induces not only high titers of long-lasting neutralizing antibodies(NAbs)but also more comprehensive T cell responses than RBD.Notably,I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant.Our study shows that the pan-epitope modified human I-R-F(I-P-R-F)vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques.Based on these promising results,we have initiated a randomized,placebo-controlled,phase Ⅰ/Ⅱ trial of the human I-P-R-F vaccine(V-01)in 180 healthy adults,and the vaccine appears safe and elicits strong antiviral immune responses.Due to its potency and safety,this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.
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