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Abstract Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with ‘any AE’ and ‘no AE’ among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities.

Summary: Intracellular organelles of mammalian cells communicate with one another during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identify voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 tethers endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and promotes clathrin-independent endocytosis, as well as endosome maturation at membrane association sites. With an optogenetics system to induce mitochondrion-endosome association, we find that, in addition to its structural role in such association, VDAC2 is functionally implicated in the promotion of endosome maturation. The mitochondrion-endosome association thus plays a role in the regulation of clathrin-independent endocytosis and endosome maturation.