Single-Dose Intranasal Vaccination Elicits Systemic and Mucosal Immunity Against SARS-CoV-2

Abstract

A safe and durable vaccine is urgently needed to tackle the COVID19 pandemic. The nasal compartment is the first barrier that needs to be breached by the SARS-CoV-2 virus before dissemination to the lung. Despite remarkable progress, current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. We report the development of an intranasal subunit vaccine that contains the spike protein and liposomal STING agonist as an adjuvant. This vaccine induces systemic neutralizing antibodies, mucosal IgA in the lung and nasal compartments, and T-cell responses in the lung of mice. Single-cell RNA- sequencing confirmed the coordinated activation of T and B cell responses in a germinal center-like manner within the nasal-associated lymphoid tissues (NALT), confirming its role as an inductive site to enable durable immunity. The ability to elicit immunity in the respiratory tract can prevent the initial establishment of infection in individuals and prevent disease transmission.Funding: This publication was supported by the NIH (U01AI148118) and Owens foundation. XLacknowledges partial funding support from the National Cancer Institute (NIH R15CA182769, P20CA221731, P20CA221696 ) and CPRIT (RP150656). The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike Glycoprotein(Stabilized) from SARS-Related Coronavirus 2, Wuhan-Hu-1, Recombinant from Baculovirus, NR 52308. Supported by the NIH/NCI under award number P30 CA016672 and used the M.D.Anderson ORION core.Conflict of Interest: UH has filed a provisional patent based on the findings in this study. All other authors have no competing interests to declare.Ethical Approval: All the animal experiments were reviewed and approved by UH IACUC.