ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing "original antigenic sin."
Subject(s)
B-Lymphocytes/immunology , B-Lymphocytes/virology , COVID-19/immunology , COVID-19/virology , Coronavirus/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Specificity , Case-Control Studies , Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins/immunology , Cross Reactions , Female , Host Microbial Interactions/immunology , Humans , Immunoglobulin G/blood , Longitudinal Studies , Male , Middle Aged , Pandemics , Phosphoproteins/immunology , Seasons , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The re-emergence of lethal coronaviruses calls for international collaboration to produce coronavirus vaccines, which are still lacking to date. Ongoing efforts to develop MERS-CoV vaccines should consider the different target populations (dromedary camels and humans) and the correlates of protection. Extending on our current knowledge of MERS, vaccination of dromedary camels to induce mucosal immunity could be a promising approach to diminish MERS-CoV transmission to humans. In addition, it is equally important to develop vaccines for humans that induce broader reactivity against various coronaviruses to be prepared for a potential next CoV outbreak.
