Systemic and mucosal IgA responses are variably induced inresponse to SARS-CoV-2 mRNA vaccination and are associatedwith protection against subsequent infection

SARS-CoV-2 is a novel and highly contagious respiratory virus that has quickly spread across the globe. The virus uses a protein called Spike and its associated receptor binding domain (RBD) to interact with angiotensin converting enzyme 2 (ACE2) on host cells1. Interaction between viral Spike/RBD and ACE2 on the cell surface is the first essential step in SARS-CoV-2 infection, and expression of ACE2 on epithelial cells of the upper respiratory tract (URT) renders them susceptible to aerosolized virus. Thus, immunity in the oral and nasal mucosa is an important first line of defense against the development of COVID-192. Saliva is an important biofluid that can provide information about the mucosal antibody (Ab) response to SARS-CoV-23. Indeed, salivary gland epithelial cells express ACE2 and harbor a significant population of IgA-producing plasma cells4. Secretory IgA (SIgA) in the saliva exists as IgA dimers that are associated with the secretory component, a proteolytic cleavage product which remains bound to IgA after it is transported across epithelial cells via the polymeric Ig receptor (pIgR)5. Secretory polymeric IgA has been shown to have potent neutralizing activity against SARSCoV-2 in vitro6. We and others have shown that IgM, IgG and IgA Ab against the SARS-CoV-2 Spike and RBD proteins are readily detected in the