Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination

Abstract

Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, SARS-CoV-2 immunity has been studied extensively in blood. However, the capacity of peripheral vaccination to generate sustained humoral and cellular immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Bronchoalveolar lavage samples obtained from vaccinated donors with or without prior infection revealed enrichment of spike-specific antibodies, class-switched memory B cells and T cells in the lung mucosa compared to the periphery in the setting of hybrid immunity, whereas in the context of vaccination alone, local anti-viral immunity was limited to antibody responses. Spike-specific T cells persisted in the lung mucosa for up to 5 months post-vaccination and multi-specific T cell responses were detected at least up to 11 months post-infection. Thus, durable lung mucosal immunity against SARS-CoV-2 seen after hybrid exposure cannot be achieved by peripheral vaccination alone, supporting the need for vaccines targeting the airways.