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The new severe acute respiratory coronavirus 2 (SARS-CoV-2), which has caused the pandemic of a life-threatening disease (COVID-19), has overwhelmed the whole world with its high transmissibility and wide range of severity. Although the use of several antiviral drugs such as paxlovid and molnupiravir has been approved by the FDA, COVID-19 vaccines still play an important role to minimize the risk of infection or even death through induction of the immune responses, especially neutralizing antibodies. However, it has been found that the recently identified SARS-CoV-2 variants of concern (VOCs) like Omicron earn new mutations on the spike protein and lead to immune evasion from the current vaccines. Though a booster dose of mRNA vaccine is still effective against the antigenically distinct variant, it is not known how well it may protect from new VOCs and/or other coronaviruses. Thus, understanding the cross-reactive immunity between different coronaviruses is a crucial step to design an effective pan-coronavirus vaccine. Understanding the cross-reactive immunity between different coronaviruses is needed before we can design a pan-coronavirus vaccine. Another coronavirus, SARS-CoV-1, which caused a global outbreak in 2003, shares 80% genomic nucleotide sequence identity with the SARS-CoV-2. We thus investigated the immunological question of cross-reactivity by comparing the serological responses between the patients infected by SARS-CoV-1 and SARS-CoV-2. Similar question was addressed from mice after immunization or infection. Our results showed that induction of cross-binding antibody to the spikes of these …