| Summary: | Abstract The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those not exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 IgG II Quant assay) and neutralizing capacities (spike SARS-CoV-2 pseudovirus Wuhan and Omicron BA.1 variant) were measured after the third and fourth doses of a COVID-19 mRNA vaccine among 46 elderly residents (median age 85 years [IQR 81; 89]) of an assisted living facility. Among participants never infected by SARS-CoV-2, the mean serum IgG levels against RBD (2025 BAU/ml), 99 days after the fourth vaccine, was as high as 76 days after the third vaccine (1987 BAU/ml), and significantly higher (p = 0.030) when the latter were corrected for elapsed time. Neutralizing antibody levels against the historical Wuhan strain were significantly higher (Mean 1046 vs 1573; p = 0.002) and broader (against Omicron) (Mean 170 vs 375; p = 0.018), following the fourth vaccine. The six individuals with an Omicron breakthrough infection mounted strong immune responses for anti-RBD and neutralizing antibodies against the Omicron variant indicating that the fourth vaccine dose did not prevent a specific adaptation of the immune response. These findings point out the value of continued vaccine boosting in the elderly population
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