Humoral response superiority of the monovalent XBB.1.5 over the bivalent BA.1 and BA.5 mRNA COVID-19 vaccines.

JN.1, the dominating SARS-CoV-2 variant, is antigenically distinct from ancestral BA.1, BA.5 and XBB.1.5 variants, raising concern about effectiveness of updated COVID-19 vaccines. Here, we compared the neutralizing antibody response against JN.1, 1-month after receipt of the three available Moderna mRNA vaccines. Sera obtained from 37, 30 and 30 XBB.1.5, BA.1 and BA.4-5 -vaccine recipients, respectively, were tested for anti-RBD IgG and for JN-1 specific neutralizing antibody levels. Geometric mean fold rise (GMFR) in JN.1 specific neutralizing titers was 27 (95 % CI: 17-43.1), 10.1 (95 % CI: 6.48-15.7) and 8.77 (95 % CI: 5.69-13.5) following XBB.1.5, BA.1 and BA.4-5 vaccines, respectively, translating into a 64 % lower adjusted response (geometric mean ratio [GMR] = 0.36, 95 % CI: 0.21-0.6) in the BA.1 arm, and a 75 % lower response (GMR = 0.25, 95 % CI: 0.15-0.43) in the BA.4-5 arm. This suggests that XBB.1.5 vaccination will most likely, result in improved effectiveness against JN.1 compared with other COVID-19 vaccines.

Immunogenicity and Reactogenicity of Coadministration of COVID-19 and Influenza Vaccines.

Importance: COVID-19 and seasonal influenza vaccines were previously given separately, although their coadministration is warranted for vaccination adherence. Limited data on their coadministration have been published. Objective: To compare the reactogenicity and immunogenicity of COVID-19 and influenza vaccinations administered together with those of COVID-19 vaccination alone. Design, Setting, and Participants: This prospective cohort study included health care workers at a large tertiary medical center in Israel who received the Influvac Tetra (Abbott) influenza vaccine (2022/2023), the Omicron BA.4/BA.5-adapted bivalent (Pfizer/BioNTech) vaccine, or both. Vaccination began in September 2022, and data were collected until January 2023. Vaccines were offered to all employees and were coadministered or given separately. Adverse reaction questionnaires were sent, and serologic samples were also collected. Exposures: Receiving COVID-19 vaccine, influenza vaccine, or both. Main Outcomes and Measures: The main outcomes for the reactogenicity analysis were symptoms following vaccine receipt, assessed by a digital questionnaire: any local symptoms; fever; weakness or fatigue; any systemic symptoms; and their duration. The immunogenicity analysis' outcome was postvaccination anti-spike IgG titer. Results: This study included 2 cohorts for 2 separate analyses. The reactogenicity analysis included 588 participants (of 649 questionnaire responders): 85 in the COVID-19 vaccine-alone group (median [IQR] age, 71 [58-74] years; 56 [66%] female); 357 in the influenza vaccine-alone group (median [IQR] age, 55 [40-65] years; 282 [79%] female); and 146 in the coadministration group (median [IQR] age, 61 [50-71] years; 81 [55%] female). The immunogenicity analysis included 151 participants: 74 participants in the COVID-19 vaccine group (median [IQR] age, 67 [56-73] years; 45 [61%] female) and 77 participants in the coadministration group (median [IQR] age, 60 [49-73] years; 42 [55%] female). Compared with COVID-19 vaccination alone, the risk of systemic symptoms was similar in the coadministration group (odds ratio, 0.82; 95% CI, 0.43-1.56). Geometric mean titers in the coadministration group were estimated to be 0.84 (95% CI, 0.69-1.04) times lower than in the COVID-19 vaccine-alone group. Conclusions and Relevance: In this cohort study of health care workers who received a COVID-19 vaccine, an influenza vaccine, or both, coadministration was not associated with substantially inferior immune response or to more frequent adverse events compared with COVID-19 vaccine administration alone, supporting the coadministration of these vaccines.

Humoral Immunity of Unvaccinated COVID-19 Recovered vs. Naïve BNT162b2 Vaccinated Individuals: A Prospective Longitudinal Study.

To study the differences in the immune response to SARS-CoV-2 infection compared to the response to vaccination, we characterized the humoral immune kinetics of these situations. In this prospective longitudinal study, we followed unvaccinated COVID-19-recovered individuals (n = 130) and naïve, two-dose BNT162b2-vaccinated individuals (n = 372) who were age- and BMI-matched for six months during the first pandemic year. Anti-RBD-IgG, neutralizing antibodies (NAbs), and avidity were assessed monthly. For recovered patients, data on symptoms and the severity of the disease were collected. Anti-RBD-IgG and NAbs titers at peak were higher after vaccination vs. after infection, but the decline was steeper (peak log IgG: 3.08 vs. 1.81, peak log NAbs: 5.93 vs. 5.04, slopes: -0.54 vs. -0.26). Peak anti-RBD-IgG and NAbs were higher in recovered individuals with BMI > 30 and in older individuals compared to individuals with BMI < 30, younger population. Of the recovered, 42 (36%) experienced long-COVID symptoms. Avidity was initially higher in vaccinated individuals compared with recovered individuals, though with time, it increased in recovered individuals but not among vaccinated individuals. Here, we show that while the initial antibody titers, neutralization, and avidity are lower in SARS-CoV-2-recovered individuals, they persist for a longer duration. These results suggest differential protection against COVID-19 in recovered-unvaccinated vs. naïve-vaccinated individuals.

Timing of Lung Transplant Referral in Patients with Severe COVID-19 Lung Injury Supported by ECMO.

Severe respiratory failure caused by COVID-19 often requires mechanical ventilation, including extracorporeal membrane oxygenation (ECMO). In rare cases, lung transplantation (LTx) may be considered as a last resort. However, uncertainties remain about patient selection and optimal timing for referral and listing. This retrospective study analyzed patients with severe COVID-19 who were supported by veno-venous ECMO and listed for LTx between July 2020 and June 2022. Out of the 20 patients in the study population, four who underwent LTx were excluded. The clinical characteristics of the remaining 16 patients were compared, including nine who recovered and seven who died while awaiting LTx. The median duration from hospitalization to listing was 85.5 days, and the median duration on the waitlist was 25.5 days. Younger age was significantly associated with a higher likelihood of recovery without LTx after a median of 59 days on ECMO, compared to those who died at a median of 99 days. In patients with severe COVID-19-induced lung damage supported by ECMO, referral to LTx should be delayed for 8-10 weeks after ECMO initiation, particularly for younger patients who have a higher probability of spontaneous recovery and may not require LTx.

Factors Associated With Protection From SARS-CoV-2 Omicron Variant Infection and Disease Among Vaccinated Health Care Workers in Israel.

Importance: A correlation between antibody levels and risk of infection has been demonstrated for the wild-type, Alpha, and Delta SARS-COV-2 variants. High rates of breakthrough infections by the Omicron variant emphasized the need to investigate whether the humoral response elicited by mRNA vaccines is also associated with reduced risk of Omicron infection and disease. Objective: To investigate whether the high antibody levels in individuals who have received at least 3 doses of an mRNA vaccine are associated with reduced risk of Omicron infection and disease. Design, Setting, and Participants: This prospective cohort study used serial real time-polymerase chain reaction (RT-PCR) and serological test data from January and May 2022 to assess the association of preinfection immunoglobin G (IgG) and neutralizing antibody titers with incidence of Omicron variant infection, incidence of symptomatic disease, and infectivity. Participants included health care workers who had received 3 or 4 doses of an mRNA COVID-19 vaccine. Data were analyzed from May to August 2022. Exposures: Levels of SARS-CoV-2 anti-receptor binding domain IgG and neutralizing antibodies. Main Outcomes and Measures: The main outcomes were incidence of Omicron infection, incidence of symptomatic disease, and infectivity. Outcomes were measured using SARS-COV-2 PCR and antigen testing and daily online surveys regarding symptomatic disease. Results: This study included 3 cohorts for 3 different analyses: 2310 participants were included in the protection from infection analysis (4689 exposure events; median [IQR] age, 50 [40-60] years; 3590 [76.6%] among female health care workers), 667 participants (median [IQR] age, 46.28 (37.44,54.8); 516 [77.4%] female) in the symptomatic disease analysis, and 532 participants (median [IQR] age, 48 [39-56] years; 403 [75.8%] female) in the infectivity analysis. Lower odds of infection were observed for each 10-fold increase in preinfection IgG (odds ratio [OR], 0.71; 95% CI, 0.56-0.90) and for each 2-fold increase in neutralizing antibody titers (OR, 0.89; 95% CI, 0.83-0.95). The odds of substantial symptomatic disease were reduced for each 10-fold increase in IgG levels (OR, 0.48; 95% CI, 0.29-0.78) and for each 2-fold increase in neutralizing antibodies levels (OR, 0.86; 95% CI, 0.76-0.96). Infectivity, assessed by mean cycle threshold value, was not significantly decreased with increasing IgG or neutralizing antibodies titers. Conclusions and Relevance: In this cohort study of vaccinated health care workers, IgG and neutralizing antibody titer levels were associated with protection against infection with the Omicron variant and against symptomatic disease.

Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study.

BACKGROUND: Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19. METHODS: In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data. FINDINGS: From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30). INTERPRETATION: Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses. FUNDING: Israeli Ministry of Health.

Immunogenicity of Omicron BA.1-adapted BNT162b2 vaccines: randomized trial, 3-month follow-up.

OBJECTIVES: The capability of the SARS-CoV-2 Omicron variant to escape immunity conferred by mRNA vaccines has led to the development of Omicron-adapted vaccines. In this study, we aimed to compare the immune response with the ancestral strain and with the BA.1 Omicron variant after administration of the original vaccine and the Omicron-adapted vaccine. METHODS: This is an ongoing phase 3, double-blinded randomized controlled trial, comparing the original BNT161b2 vaccine, monovalent Omicron BA.1-adapted BNT161b2 vaccine, and bivalent combinations. Each vaccine was given at a 30 µg and 60 µg dose. Primary outcomes considered included neutralization titers of SARS-CoV-2 ancestral strain and Omicron BA.1. Exploratory endpoints included neutralization titers for Omicron BA.5, and the incidence of COVID-19 cases. RESULTS: Overall, 122 individuals (22, 19, 20, 20, 20, 20, and 21 in each arm) completed a 90-day follow-up. Three months after vaccination, adjusting for baseline levels, neutralizing antibody titers were 0.63 (95% CI: 0.3-1.32) and 0.54 (0.24-1.2) for monovalent/60 µg, 0.9 (0.42-1.92) and 2.69 (1.17-6.17) times for monovalent-Omi.BA.1/30 µg, 1.28 (0.6-2.75) and 2.79 (1.21-6.41) times for monovalent-Omi.BA.1/60 µg, 0.96 (0.46-1.97) and 2.07 (0.93-4.58) times for bivalent-Omi.BA.1/30 µg, and 0.79 (0.38-1.63) and 1.95 (0.88-4.32) times for bivalent-Omi.BA.1/60 µg when compared with BNT162b2/30 µg against the ancestral strain and BA.1 variant, respectively. DISCUSSION: BA.1-adapted mRNA vaccines lead to a stronger neutralizing antibody response against the Omicron BA.1 sub-variant.

The Use of Rapid COVID-19 Antigen Test in the Emergency Department as a Decision-Support Tool.

The emergency department (ED) is the initial point of contact between hospital staff and patients potentially infected with SARS-CoV-2, thus, prevention of inadvertent exposure to other patients is a top priority. We aimed to assess whether the introduction of antigen-detecting rapid diagnostic tests (Ag-RDTs) to the ED affected the likelihood of unwanted SARS-CoV-2 exposures. In this retrospective single-center study, we compared the rate of unwarranted exposure of uninfected adult ED patients to SARS-CoV-2 during two separate research periods; one before Ag-RDTs were introduced, and one with Ag-RDT used as a decision-support tool. The introduction of Ag-RDTs to the ED significantly decreased the relative risk of SARS-CoV-2-negative patients being incorrectly assigned to the COVID-19 designated site ("red ED"), by 97%. There was no increase in the risk of SARS-CoV-2-positive patients incorrectly assigned to the COVID-19-free site ("green ED"). In addition, duration of ED admission was reduced in both the red and the green ED. Therefore, implementing the Ag-RDT-based triage protocol proved beneficial in preventing potential COVID-19 nosocomial transmission.

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

The Association Between Prebooster Vaccination Antibody Levels and the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The correlation between anti-severe acute respiratory syndrome coronavirus 2 antibody levels and infection was reported. Here, we estimated the role of pre-fourth dose levels using data from 1098 healthcare workers. The risk of infection was reduced by 46% (95% confidence interval, 29%-59%) for each 10-fold increase in prebooster levels. Prebooster antibody levels could be used to optimally time boosters.

Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up.

Booster doses for the ongoing COVID-19 pandemic are under consideration in many countries. We report a three-month follow-up of 700 participants in a fourth vaccine dose study, comparing BNT162b2 and mRNA1273, administered four months after a third BNT162b2 dose. The primary outcomes are the levels of IgG, neutralizing antibodies, and microneutralization and the secondary outcomes are the levels of IgA and T cell activation, and clinical outcomes of SARS-CoV-2 infection and substantial symptomatic disease. Waning of the immune response is evident during follow-up, with an 11% (ß = 0.89, 95% CI, 0.88-0.9) and 21% (ß = 0.79, 95% CI, 0.76-0.82) multiplicative decay per week of IgG and neutralizing antibodies, respectively, in the mRNA1273 group, and of 14% (ß = 0.86, 95% CI, 0.86-0.87) and 26% (ß = 0.74, 95% CI, 0.72-0.76), respectively, in the BNT162b2 group. Direct neutralization of Omicron variants is low relative to ancestral strains. Cumulatively over the study period, both vaccines show little efficacy against infection but were highly efficacious against substantial symptomatic disease [89% [(IRR 0.11, 95% CI, 0.02-0.37) and 71% (IRR 0.29, 95% CI, 0.13-0.57) for mRNA1273 and BNT162b2, respectively]. These results are informative for further boosting policy-making. Trial registration numbers (clinicaltrials.gov): NCT05231005 and NCT05230953.

High Immune Response Rate to the Fourth Boost of the BNT162b2 Vaccine against the Omicron Variants of Concern among Liver Transplant Recipients.

The immune response of liver transplant (LT) recipients to a third dose of the BNT162b2 mRNA vaccine significantly waned after four months. We aimed to evaluate the immune response and breakthrough infection rates of a fourth dose against the Omicron variants among LT recipients. LT recipients who had no past or active SARS-CoV-2 infection and received three doses of the BNT162b2mRNA vaccine were included. Of the 73 LT recipients, 50 (68.5%) received a fourth dose. The fourth dose was associated with a significantly higher positive immune response than the third dose. Receptor-binding domain (RBD) IgG and Omicron BA.1 and BA.2 neutralizing antibodies were determined at a median of 132 and 29 days after the third and fourth vaccines. They were 345 binding antibody units per milliliter (BAU/mL) vs. 2118 BAU/mL (p < 0.0001), 10 vs. 87 (p < 0.0001), and 15 vs. 149 (p = 0.001), respectively. Breakthrough infections were documented among nine (18%) LT recipients after the fourth dose and among seven (30.4%) patients following the third dose (p = 0.2); 93.5% of breakthrough infections were mild. The infection rate after the fourth dose was higher among diabetic vs. nondiabetic recipients (33.3% vs. 6.9%, respectively; p = 0.02). Further studies are needed to evaluate additional factors influencing the breakthrough infection rate among LT recipients.

Omicron BA.2.75 variant is efficiently neutralised following BA.1 and BA.5 breakthrough infection in vaccinated individuals, Israel, June to September 2022.

We evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.5 and BA.2.75) in fully vaccinated (three doses of Comirnaty vaccine) healthcare workers (HCW) in Israel who had breakthrough BA.1/BA5 infections. Omicron breakthrough infections in vaccinated individuals resulted in increased neutralising antibodies against the WT and Omicron variants compared with vaccinated uninfected HCW. HCW who recovered from BA.1 or BA.5 infections showed similar neutralising antibodies levels against BA.2.75.

Real-World Immunogenicity and Reactogenicity of Two Doses of Pfizer-BioNTech COVID-19 Vaccination in Children Aged 5-11 Years.

There are limited data concerning the immunogenicity and reactogenicity of COVID-19 vaccines in children. A total of 110 children, 5-11 years old were vaccinated with two doses (with a 3-week interval between doses) of the Pfizer-BioNTech COVID-19 vaccine and were followed for 21, 90, and 180 days after vaccination for immunogenicity, adverse events, and breakthrough infections. Ninety days after the first vaccine dose, the GeoMean (CI 95%) of IgG ascended to 1291.0 BAU (929.6-1790.2) for uninfected children and 1670.0 BAU (1131.0-2466.0) for Infected children. One hundred and eighty days after receiving the first dose of the vaccine, the titers decreased to 535.5 BAU (288.4-993.6) for the uninfected children, while only a small decline was detected among infected children-1479.0 (878.2-2490.0). The neutralizing antibodies titer almost did not change over time in the uninfected children, and even elevated for the infected children. Of the 110 vaccinated children, 75.5% were infected, with only mild COVID-19 infection symptoms. Child vaccination was found to be safe, with mild, mostly local, and of short duration, reported AEs. No serious adverse events (SAEs) were reported after vaccination. The durability of two doses of vaccine in children is longer, thus a booster may not be needed as early as in adults.

Comparing immunogenicity and efficacy of two different mRNA-based COVID-19 vaccines as a fourth dose; six-month follow-up, Israel, 27 December 2021 to 24 July 2022.

We assess the immunogenicity and efficacy of Spikevax and Comirnaty as fourth dose COVID-19 vaccines. Six months post-fourth-dose, IgG levels were higher than pre-fourth dose at 1.58-fold (95% CI: 1.27-1.97) in Spikevax and 1.16-fold (95% CI: 0.98-1.37) in Comirnaty vaccinees. Nearly 60% (159/274) of vaccinees contracted SARS-CoV-2. Infection hazard ratios (HRs) for Spikevax (0.82; 95% CI: 0.62-1.09) and Comirnaty (0.86; 95% CI: 0.65-1.13) vaccinees were similar, as were substantial-disease HRs, i.e. 0.28 (95% CI: 0.13-0.62) and 0.51 (95% CI: 0.27-0.96), respectively.

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

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: In 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 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 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/106 peripheral blood mononuclear cells to 59 (9.3) T cells/106 peripheral blood mononuclear cells. Conclusions and Relevance: This study found that the third vaccine dose was associated with greater durability than the second dose; however, Omicron was associated with greater resistance to neutralization than wild type and Delta variants of concern. Humoral response dynamics were associated with susceptibility to Omicron infection.