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In the mouse model experiments, a booster dose consisting of intramuscular mRNA, intranasal recombinant spike trimer protein plus cGAMP adjuvant (a STING agonist) or intranasal adenovirus-vector encoding the ancestral spike (AD5-S) was administered to mice previously vaccinated with 2 doses of intramuscular mRNA vaccine shots. These observations are an important addition to other studies that have reported superior mucosal (saliva) antibodies in those with prior COVID-19 than vaccinated individuals ( 4) and the establishment of tissue-resident T cells for up to 6 months after infection ( 5). Moreover, the vaccinated group had substantially fewer BAL tissue-resident spike-specific memory CD4 T, CD8 T, and RBD-specific memory B cells than the group with prior COVID-19. The vaccinated group, despite having comparable circulating neutralizing antibodies against D614G, delta, and omicron variants, had significantly lower neutralizing titers against all variants in the BAL compared to the convalescent group. Notably, the mean age of the participants was 70 years and similar for the three groups.
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In the human part of the study, 19 vaccinated participants were compared with 10 who had convalesced from COVID-19 and 5 who were unvaccinated. Beyond the conventional parameters of circulating antibodies, B and T cell immunity in the blood, this elegant study assessed bronchoalveolar lavage (BAL) fluid immunity to specifically characterize the lower respiratory mucosa, tissue-resident memory B and T cells that are part and parcel of protection.