MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. This IgA antibody binds to SARS-CoV-2 RBD with high affinity competing at the ACE2 binding interface by blocking interactions with the receptor. In the current study, we describe the discovery of a cross-neutralizing human IgA monoclonal antibody, MAb362 IgA. How precisely which isotype may protect the mucosa from SARS-CoV-2 infection remains an open question. In animal models, high titers of mucosal IgA in the lung is correlated with reduced pathology upon viral challenge with SARS-CoV 19. In addition, the diverse, high level of glycosylation of IgA antibodies, further protects the mucosal surface with non-specific interference. The avidity of mucosal IgA, in comparison with IgG, owing to the multimeric structure, enhances the antibody binding with antigens.
This enhancement is likely facilitated by the Fc domain of IgG but not for its isotype variant IgA 18. Several anti-SARS-CoV MAbs have demonstrated cross-neutralizing activities against the S protein of SARS-CoV-2 16, 17.Īntibody-dependent enhancement of viral infections are one of the major hurdles in the development of effective vaccines. We and others have demonstrated that neutralizing MAbs that block RBD-ACE2 binding could confer potent protection against SARS-CoV as both prophylaxis and treatment in various animal models 7, 9, 10. Most current anti-SARS-CoV MAbs neutralize virus by binding to epitopes on the spike protein RBD of SARS-CoV 15. The receptor-binding domain (RBD) of the S protein facilitates viral entry into human cells through human angiotensin-converting enzyme 2 (ACE2) receptor binding leveraging a similar mechanism as SARS-CoV 12, 13, 14. These anti-coronavirus MAbs primarily target the viral spike (S) glycoprotein, a type I transmembrane glycoprotein that produces recognizable crown-like spike structures on the virus surface. The feasibility of human monoclonal antibodies (MAbs) as immunoprophylaxis or therapy against coronaviruses including SARS-CoV 7, 8, 9, 10 and MERS-CoV 11 has been demonstrated. Although concerns, as occurred with SARS-CoV 5, 6, that vaccines may cause disease enhancement still need to be addressed. Pre- or post-exposure immunotherapies with neutralizing antibodies, would be of great use by providing immediate mucosal immunity against SARS-CoV-2. Interventions for the prevention or treatment of COVID-19 are crucial for the ongoing outbreak. Phylogenic analysis has classified SARS-CoV-2 within the sarbecoviruses subgenus, the β lineage that also contains SARS-CoV, sharing ~79.6% sequence identity 4. Within 3 months of the first report cases, COVID-19 rapidly disseminated through the human population and had become a global pandemic by March 2020. The coronavirus disease 2019 (COVID-19) ranges from mild to severe acute respiratory infection, with a fatality rate estimated to range from 2 to 3% 1, 2, 3, 4.
In December 2019, a novel coronavirus (SARS-CoV-2) was identified as the cause of an outbreak of acute respiratory infections. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. Nature Communications volume 11, Article number: 4198 ( 2020)ĬOVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity.
A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction
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