CVR - Coronavirus Vaccines R&D Roadmap

Milestone
2.2.c

Mucosal vs. systemic humoral immunity

In progress

Determine the relative roles of mucosal (e.g., in the upper and lower respiratory and gastrointestinal tracts) versus systemic immunity in protecting against coronavirus infection and limiting the potential for virus transmission. 

Progress Highlights

See CVR Scholar Hub page: Mucosal vs. Systemic Immunity to Coronaviruses

Located in upper and lower respiratory tracts, acting as the primary barrier against SARS-CoV-2 

Secretory IgA (sIgA) neutralizes SARS-CoV-2 at mucosal surfaces, preventing viral attachment and replication in the nasal epithelium, and reducing viral load in aerosols and droplets. 

Mucosal IgA and IgG, produced locally after infection or vaccination, prevent viral spread to the lower respiratory tract, lowering severe disease risk.

Mucosal IgA peaks post-infection/vaccination, but wanes within months.

Induced by intranasal vaccines, reducing mucosal viral shedding and transmission.

Mucosal memory B and T cells provide rapid localized immunity, but are shorter-lived.

Greater T cell recruitment, and TRM T cell cell counts in the airways is linked to milder disease and lower viral pulmonary loads.

Circulates through blood and lymph, providing systemic protection and reducing disease severity. Systemic IgG provides robust protection against severe disease by neutralizing circulating SARS-CoV-2 and limiting systemic spread.

Systemic IgG plays a limited role in reducing viral shedding at mucosal surfaces due to less efficient transport into respiratory secretions compared to sIgA.

Long-lasting protection with memory B cells maintaining immunity for over a year.

Induced by systemic vaccines, producing high IgG titers, but limited mucosal IgA.

Ensures rapid secondary response upon reinfection, but less effective at preventing initial mucosal infection.

Eser 2023 found that higher frequencies of circulating nucleocapsid-specific T cells (CD4⁺ and CD8⁺) in a patient’s blood during the first week of infection correlates with lower viral loads in the upper airway.

NIAID Project Nextgen Phase 1/2a trials were established to evaluate a range of immunological assays to increase understanding of mucosal immunity as it relates to SARS-Cov-2 and other coronavirus vaccines.