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

Abstract

IMPORTANCEThe 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 PARTICIPANTSIn a prospective longitudinal cohort study in a tertiary medical center in Israel, health care workers who received the BNT162b2 vaccine were followed up monthly for IgG 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, T cell 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 MEASURESThe 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 chain reaction. RESULTS Overall, 4868 health care workers (mean [SD] age, 46.9 [13.7] years; 3558 [73.1%] women) and 3972 health care workers (mean [SD] 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 IgG 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 IgG 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 IgG 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 IgG 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 (SD) T cell activity decreased from 98 (5.4) T cells/10 6 peripheral blood mononuclear cells to 59 (9.3) T cells/10 6 peripheral blood mononuclear cells. (continued) Key Points Question What is the durability of the immune response after 3 vaccine doses, and are antibody kinetics associated with SARS-CoV-2 Omicron infection? Findings In this cohort study of 3972 health care workers, reduction in antibody levels 5 months after the third BNT16...

Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine

“…Our findings that the higher durability of antibody titers after the 3-dose of mRNA vaccine than after 2-dose is consistent with a previous study of Israeli healthcare workers [3] and compatible with the effectiveness studies of mRNA vaccines showing a slower waning of VE for infection over time in recipients of 3-dose relative to those of 2-dose [15, 16]. In addition, we found that hybrid immunity (vaccination and infection) has added durability over the immunity induced by vaccination alone.…”

“…Epidemiological data are scarce regarding the waning pattern of humoral immunity following 2-and 3-dose COVID-19 vaccination and its related factors. Studies among 2-dose recipients showed that anti-SARS-CoV-2 spike antibody titers waned faster in older age [4] and female sex [3] and slower in those with a history of COVID-19 [5], but no such investigation has been done for 3-dose. It remains elusive for both doses whether the waning speed of antibody differs depending on obesity [6,7], comorbid conditions [7,8], immunosuppression [7,8], or behavioral factors (smoking and alcohol drinking [9][10][11]), which have been linked to lower immune response to COVID-19 vaccine.…”

“…The widespread use of primary (1- to 2-dose) and booster (3-dose) vaccinations against coronavirus disease 2019 (COVID-19) substantially decreased the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization [1, 2]. With the waning of vaccine-induced humoral immunity over time [3], however, vaccine effectiveness (VE) of 2- and 3-dose for infection has decreased [1, 2]. Understanding the duration of vaccine-induced immunity and factors accelerating the waning is critical for formulating vaccine policy, including the recommendation regarding the timing and target of an additional booster dose.…”

210-Day Kinetics of Total, IgG, and Neutralizing Spike Antibodies across a Course of 3 Doses of BNT162b2 mRNA Vaccine

“…Furthermore, we found that the AT50 of IgG and N-Ab responses were longer following the third dose than after the second dose. Other studies [ 18 ] have also demonstrated a similar pattern where waning of both IgG and N-Ab was slower after the third compared to the second dose (IgG 1.32% vs. 2.26% per day and N-Ab 1.32% vs. 3.34% per day). Given that total S-Ab exhibited a shorter AT50 than IgG post-booster, both antibody levels may need to be assessed to observe the waning antibody levels post-vaccination, and IgG may be the preferred antibody to follow-up for long-term antibody response.…”

Efficacy of the wild-type/Omicron BA.1 bivalent vaccine as the second booster dose against Omicron BA.2 and BA.5

“…The comparison between the results of our previous report and our current study after the first booster dose led to an inference that the original monovalent vaccine rapidly loses immunity against Omicron (10). This inference conforms with reports based on similar studies (14, 19). In fact, vaccine effectiveness waned remarkably within a few months of administration in clinical settings (20, 21).…”