Durability of Immune Response After COVID-19 Booster Vaccination and Association With COVID-19 Omicron lnfection

IMPORTANCE: The BNT162b2 two-dose vaccine (BioNTech/Pfizer) has high effectiveness that wanes within several months. The third dose is effective in mounting a significant immune response. but its durability is unknown.
OBJECTIVE: To compare antibody waning after second and third doses and estimate the association of antibody kinetics with susceptibility to infection with the Omicron variant of SARS-CoV-2.
DESIGN, SETTING, AND PARTICIPANTS: ln a prospective longitudinal cohort study iח a tertiary medical center in lsrael. health care workers who received the BNT162b2 vaccine were followed up monthly for lgG and neutralizing antibody levels. Linear mixed models were used to compare antibody titer waning of second and third doses and to assess whether antibody dynamics were associated with Omicron transmission. Avidity. זcell activation. and microneutralization of sera against different variants of concern were assessed for a subgroup.
EXPOSURE: Vaccination with a booster dose of the BNT162b2 vaccine.
MAIN OUTCOMES AND MEASURES The primary outcome was the rate of antibody titer change over time. and the secondary outcome was SARS-CoV-2 Omicron variant infection. as confirmed by reverse transcriptase-polymerase חiahcreaction.
RESULTS: Overall. 4868 health care workers (mean [SD] age, 46.9 [13.7] years; 3558 [73.1%] women) and 3972 health care workers (mean [5D] age. 48.5 [14.1] years; 996 [74.9%] women) were followed up for 5 months after their second and third vaccine doses. respectively. Waning of lgG levels was slower after the third compared with the second dose (1.32%/d [95% CI. 1.29%/d to 1.36%/d] vs 2.26% [95% CI. 2.13%/d 2.38%/d]). as was waning of neutralizing antibody levels (1.32%/d [95% CI. 1.21%/d to 1.43%/d] vs 3.34%/d [95% CI. 3.11%/d to 3.58%/d]). Among 2865 health care workers assessed for Omicron incidence during an additional 2 months of follow-up. lower lgG peak (ratio of means 0.86 [95% CI. 0.80-0.91]) was associated with Omicron infection. and among participants aged 65 years and older. faster waning of lgG and neutralizing antibodies (ratio of mean rates. 1.40; [95% CI. 1.13-1.68] and 3.58 [95% CI. 1.92-6.67]. respectively) were associated with Omicron infection. No waning in lgG avidity was observed 112 days after the third dose. Live neutralization of Omicron was lower compared with previous strains. with a geometric mean titer at the peak of 111 (95% CI. 75-166). compared with 942 (95% CI. 585-1518) for WT. 410 (95% CI. 266-634) for Delta; it demonstrated similar waning to 26 (95% CI. 16-42) within 4 months. Among 77 participants tested for T cell activity. mean (5D) T cell activity decreased from 98 (5.4) T cells/106 peripheral blood mononuclear cells to 59 (9.3) T cells/106 peripheral blood mononuclear cells.