Neutralizing antibodies to SARS-CoV-2 Omicron variant after 3rd mRNA vaccination in health care workers and elderly subjects and response to a single dose in previously infected adults

ABSTRACT

The emergence of SARS-CoV-2 Omicron variant (B.1.1.529) with major spike protein mutations has raised concern over potential neutralization escape and breakthrough infections among vaccinated and previously SARS-CoV-2 infected subjects. We measured cross-protective antibodies against variants in health care workers (HCW, n=20) and nursing home residents (n=9) from samples collected 1-2 months following the booster (3rd) dose. We also assessed the antibody responses in prior to Omicron era infected subjects (n=38) with subsequent administration of a single mRNA vaccine dose. Following booster vaccination HCWs had high IgG antibody concentrations to the spike protein and neutralizing antibodies (NAb) were detectable against all variants. IgG concentrations among the elderly remained lower, and some lacked NAbs against the Beta and Omicron variants. NAb titers were significantly reduced against Delta, Beta and Omicron compared to wild-type virus regardless of age. Vaccination induced high IgG concentrations and variable titers of cross-reactive NAbs in previously infected subjects, whereas NAb titers against Omicron were barely detectable 1-month post-infection. High IgG concentrations with cross-protective neutralizing activity were detected after three COVID-19 vaccine doses in HCWs. However, lower NAb titers seen in the frail elderly suggest inadequate protection against Omicron breakthrough infections, yet protection against severe COVID-19 is expected. O_TBL View this table org.highwire.dtl.DTLVardef@84f4c4org.highwire.dtl.DTLVardef@e1a056org.highwire.dtl.DTLVardef@e5a4ecorg.highwire.dtl.DTLVardef@ae8370org.highwire.dtl.DTLVardef@137480e_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONGeometric mean IgG concentrations, GMC [95% CI] expressed as BAU/ml for spike proteins (SFL and RBD) and geometric mean titers, GMT [95% CI] of neutralizing antibodies (NAb) against wild-type (WT) virus and three variants of concern Delta (B.1.617.2), Beta (B.1.351) and Omicron (B.1.1.529) in elderly (n=7-9) and health care workers (HCW) 21-42 (n=7) or 43-77 (n=8) days post booster mRNA vaccination (3rd dose of Comirnaty). C_TABLECAPTION C_TBL Clinical trial registrationEudraCT 2021-004788-29