Durability of immune response after COVID-19 booster vaccination and association with COVID-19 omicron infection
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Abstract
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.
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The waning of neutralising antibodies induced by mRNA vaccines has been associated with increased susceptibility to infection with the omicron variant of SARS-CoV-2.
“The waning of neutralising antibodies induced by mRNA vaccines has been associated with increased susceptibility to infection with the omicron (B.1.1.529)variant of SARS-CoV-2.23”
From Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial (2024) · cites this paper as [23]
The Results (Association Between IgG Antibody Levels and Susceptibility to Omicron Infection) report faster neutralizing-antibody decline among infected than uninfected participants aged 65 or older. The Discussion likewise limits the observed association between waning and Omicron transmission to at least that age group. The citing sentence leaves out this population qualifier and presents the association more generally. (LLM, conf=0.87)
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- Authors
- Gilboa, M., Regev-Yochay, G., Mandelboim, M., Indenbaum, V., Asraf, K., Fluss, R., Amit, S., Mendelson, E., Doolman, R., Afek, A., Freedman, L. S., Kreiss, Y., & Lustig, Y.
- Affiliations
- Tel Aviv University (IL)
- Infection Prevention and Control Unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
- Corresponding author
- Gilboa, Mayan
- ORCID
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2022-09-15
- Volume
- 5
- Issue
- 9
- Pages
- e2231778
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC9478782
- OpenAlex
- W4295898295
- Cited by
- 128
- References
- 30
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 37 · 2023: 55 · 2022: 14 · 2021: 1
- FWCI
- 14.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- COVID-19 booster vaccination, BNT162b2, antibody waning, neutralizing antibodies, IgG, Omicron variant, COVID-19 pandemic, vaccine durability, healthcare workers, antibody avidity, microneutralization, T cell response, breakthrough infection, vaccine effectiveness, vaccine hesitancy
- MeSH terms
- COVID-19, SARS-CoV-2, BNT162 Vaccine, Adult, Antibodies, Viral, Female, Humans, Immunoglobulin G, Immunity, Leukocytes, Mononuclear, Longitudinal Studies, Male, Middle Aged, Prospective Studies, RNA-Directed DNA Polymerase, Vaccination, Antibodies, Neutralizing
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