Biomaterial Database

SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity. 2024

Ninaad Lasrado, and Marjorie Rowe, and Katherine McMahan, and Nicole P Hachmann, and Jessica Miller, and Catherine Jacob-Dolan, and Jinyan Liu, and Brookelynne Verrette, and Kristin A Gotthardt, and Darren M Ty, and Juliana Pereira, and Camille R Mazurek, and Amelia Hoyt, and Ai-Ris Y Collier, and Dan H Barouch

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections.