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Jinyi Tang, Cong Zeng, Thomas M Cox, Chaofan Li, Young Min Son, In Su Cheon, Supriya Behl, Taylor J Justin, Rana Chakaraborty, Aaron J Johnson, Dante N Shiavo, James P Utz, Janani S Reisenauer, David E Midthun, John J Mullon, Eric S Edell, Robert S Vassallo, Ryan Kern, Shan-lu Liu, Jie Sun, Respiratory humoral and cellular immune responses following COVID-19 mRNA vaccination, The Journal of Immunology, Volume 208, Issue Supplement_1, May 2022, Page 65.22, https://doi.org/10.4049/jimmunol.208.Supp.65.22
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Abstract
Vaccination is the key for controlling COVID-19 pandemic. SARS-CoV-2 mRNA vaccines have been demonstrated to induce robust and persistent humoral and cellular immunity in the circulation, but the vaccine-induced immune responses in the respiratory tract remain largely elusive. Here, we examined SARS-CoV-2 S-specific antibody, B and T cell immune responses in the bronchoalveolar lavage (BAL) fluid and blood from unvaccinated, COVID-19 vaccinees or COVID-19 convalescents that recovered from prior moderate to severe SARS-CoV-2 infection. We found that mRNA vaccination induced significant SARS-CoV-2 S-specific CD4+ and CD8+ T cell responses in the blood but not in the BAL. Similarly, mRNA vaccination failed to provoke detectable SARS-CoV-2 S RBD-specific B cell responses in the BAL despite marked RBD-specific B cells were observed in the blood of COVID-19 vaccinees. In contrast, robust SARS-CoV-2 S-specific B and T cell responses were present in the BAL of COVID-19 convalescents. Furthermore, significant neutralizing antibody responses were only observed in the BAL from convalescents but not vaccinees, while both COVID-19 vaccinee and convalescent groups mounted marked neutralizing antibody responses in the blood. Thus, despite their induction of robust circulating humoral and cellular immunity, the current COVID-19 vaccines provoke relatively weak cellular and neutralizing antibody responses in the lower respiratory tract. Our results indicate that a mucosal booster vaccine may be needed to establish robust immunity in the respiratory mucosa, which could provide a strong first line of defense against SARS-CoV-2 re-infection.