Abstract
To face the continuous emergence of SARS-CoV-2 variants, broadly protective therapeutic antibodies are highly needed. We here focused on the fusion peptide (FP) region of the viral spike antigen since it is highly conserved among alpha- and betacoronaviruses. First, we found that coronavirus cross-reactive antibodies are commonly formed during infection, being omnipresent in sera from COVID-19 patients, in ~50% of pre-pandemic human sera (rich in antibodies against endemic human coronaviruses), and even in feline coronavirus-infected cats. Pepscan analyses demonstrated that a confined N-terminal region of the FP is strongly immunogenic across diverse coronaviruses. Peptide-purified human antibodies targeting this conserved FP epitope exhibited broad binding of alpha- and betacoronaviruses, besides weak and transient SARS-CoV-2 neutralizing activity. Being frequently elicited by coronavirus infection, these FP-binding antibodies might potentially exhibit Fc-mediated effector functions and influence the kinetics or severity of coronavirus infection and disease.
Highlights
The outcome of infection with SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), varies widely from asymptomatic to acute respiratory distress syndrome leading to death
To quantify coronavirus cross-reactive antibodies in human sera, we developed immunoperoxidase monolayer assays (IPMA) in cells that were either infected with virus (HCoV-OC43 or HCoV229E) or transfected with an expression plasmid for V5-tagged SARS-CoV-2 S or N protein, which avoided biosafety level-3 manipulation of live SARS-CoV-2 (Figure 1A)
We analyzed a series of 23 serum samples from seven COVID-19 patients, hospitalized during the first pandemic wave in Belgium in 2020 (SARS-CoV-2 room temperature (RT)-qPCR positive patients I-O; sera taken between day 2 and 18 after onset of symptoms)
Summary
The outcome of infection with SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), varies widely from asymptomatic to acute respiratory distress syndrome leading to death. Since adolescents and children under 5 years of age exhibit the highest infection frequency by endemic human coronaviruses (eHCoVs) [3, 4], the hypothesis has been raised that the immune response induced by these viruses might offer some levels of cross-protection against SARS-CoV-2 [4,5,6]. SARS-CoV-2 is the seventh coronavirus known to infect humans, besides HCoV-OC43, -229E, -NL63, -HKU1, severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). HCoV-OC43 is the most prevalent eHCoV and accounts, together with HCoV-229E, for about 30% of all common colds This explains the high seroprevalence for these two viruses in the adult population [3, 4, 9,10,11,12]
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