Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2

Abstract

Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.

Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection

“… 1 Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) boosts mucosal IgA responses, 2 and neutralizing IgA, including neutralizing IgA against the B.1.1.529 (omicron) variant of SARS-CoV-2, has been detected after infection with wild-type SARS-CoV-2. 3 However, the potential role of mucosal IgA in protection against SARS-CoV-2 infection is still largely unknown.…”

Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity

“…The high IgA titers against HR1 are intriguing. Interestingly, although IgG are about five times more abundant in serum than IgA, several studies showed higher neutralizing activities for IgA purified from sera of infected individuals compared to their IgG counterparts [64] , [65] . Whether IgA against HR1 display neutralizing function will need further investigation.…”

A Bacteriophage-Based, Highly Efficacious, Needle- and Adjuvant-Free, Mucosal COVID-19 Vaccine

“…It is intriguing why the neutralization activity induced by T4-CoV-2 vaccination is so broad. The reasons for this finding require further investigation, especially if it relates to the presence of high levels of IgA in the serum and sIgA in BALF, which are reported to be more potent than IgG in neutralizing SARS-CoV-2 virus ( 14 , 64 ).…”