Abstract
With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.
Keywords: COVID-19; SARS-CoV-2; TLR7 agonist; adjuvant-protein conjugate; recombinant protein vaccine.
【저자키워드】 COVID-19, SARS-CoV-2, TLR7 agonist, adjuvant-protein conjugate, recombinant protein vaccine., 【초록키워드】 coronavirus disease, neutralizing antibody, Vaccine, immune response, Diseases, Neutralizing antibodies, TLR7, variants of concern, Toxicity, omicron, immune, Spike protein, Antigen, global pandemic, Protein, cellular immunity, mice, SARS-CoV-2 spike protein, Research, Cluster, vaccine candidate, Alpha, Beta, adjuvant, B.1.1.529, disease, New coronavirus, S1 subunit, Safe, humoral, Conjugates, S1 protein, Effect, Prevent, effective, facilitate, induce, triggered, the vaccine, expected, 【제목키워드】 concern, potent, agonist, conjugate,