Abstract
The COVID-19 pandemic caused by SARS-CoV-2 has a significant burden on the economy and healthcare around the world. Vaccines are the most effective tools to fight infectious diseases by containing the spread of the disease. The current vaccines against SARS-CoV-2 are mostly based on the spike protein of SARS-CoV-2, which is large and has many immune-dominant non-neutralizing epitopes that may effectively skew the antibody response towards non-neutralizing antibodies. Here, we have explored the possibility of immune-focusing the receptor binding motif (RBM) of the spike protein of SARS-CoV-2 that induces mostly neutralizing antibodies in natural infection or in vacinees. The result shows that the scaffolded RBM can bind to Angiotensin Converting Enzyme 2 (ACE2) although with low affinity and induces a strong antibody response in mice. The immunized sera can bind both, the receptor binding domain (RBD) and the spike protein, which holds the RBM in its natural context. Sera from the immunized mice showed robust interferon γ response but poor neutralization of SARS-CoV-2 suggesting presence of a predominant T cell epitope on scaffolded RBM. Together, we provide a strategy for inducing strong antigenic T cell response which could be exploited further for future vaccine designing and development against SARS-CoV-2 infection.
Keywords: Immuno-focusing; RBD; SARS-CoV-2; Scaffold; Vaccine.
【저자키워드】 SARS-CoV-2, Vaccine, RBD, Immuno-focusing, Scaffold, 【초록키워드】 neutralizing antibody, ACE2, Vaccine, neutralization, SARS-COV-2 infection, COVID-19 pandemic, Antibody Response, Infectious disease, Receptor binding domain, Spread, T cell, mice, sera, healthcare, natural infection, epitope, receptor binding motif, T cell response, angiotensin, Non-neutralizing antibodies, interferon γ, antigenic, immunized mice, effective, immunized, robust, caused, the disease, the spike protein, induce, predominant, the antibody response, non-neutralizing epitope, RBM, 【제목키워드】 Vaccine, Protein, receptor binding motif, approach,