Durability of Immune Response After COVID-19 Booster Vaccination and Association With COVID-19 Omicron Infection
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Abstract
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/10 6 peripheral blood mononuclear cells to 59 (9.3) T cells/10 6 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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SciScore for 10.1101/2022.05.03.22274592: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethical Statement: The protocol was approved by the Institutional Review Board of the Sheba Medical
Consent: Centre (SMC) and written informed consent was obtained from all study participants.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources To present all IgG Antibody levels in Binding Antibody Units (BAU) per the World Health Organization (WHO) standard measurements we imputed the Abott-based BAU values from the Beckman-Coulter assay results, based on an independent sample of individuals with both Abbott BAU and Beckman-Coulter levels (see Supplementary Methods). …SciScore for 10.1101/2022.05.03.22274592: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethical Statement: The protocol was approved by the Institutional Review Board of the Sheba Medical
Consent: Centre (SMC) and written informed consent was obtained from all study participants.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources To present all IgG Antibody levels in Binding Antibody Units (BAU) per the World Health Organization (WHO) standard measurements we imputed the Abott-based BAU values from the Beckman-Coulter assay results, based on an independent sample of individuals with both Abbott BAU and Beckman-Coulter levels (see Supplementary Methods). Abbottsuggested: (Abbott, RRID:SCR_010477)Graphical presentation: Scatter plots of IgG and neutralizing antibody levels since the receipt of the second and third doses were created with the use of GraphPad Prism software, version 9.0 (GraphPad Software). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Statistical analysis was performed using SAS software, version 9.4 (SAS Institute), SASsuggested: (SASqPCR, RRID:SCR_003056)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has several limitations, first as all participants are health care workers, they are relatively younger and healthier than the general population, thus potentially limiting its generalizability. Second, the study period following waning was relatively short. Further studies to assess waning after longer periods are needed. Furthermore, as participants were not blinded to their serology testing, those who had lower serological markers, could have potentially had a lower threshold for PCR testing and this might have created a bias. Yet, during the study period, due to the outstanding surge in cases, all HCW, regardless of their serological tests, were encouraged to obtain a weekly RT-PCR SARS-COV test in addition to testing after exposure or due to symptoms. Numerous studies showed that mRNA vaccines played a major role in protecting the world population against COVID-19. We demonstrate here that the humoral response following a third dose is sustained for months with only minor reduction in antibody levels and that infection with omicron VOC is correlated with antibody level and thus, potentially, might be predicted. Nevertheless, our results clearly show that the humoral response generated by vaccination may not be enough to protect against Omicron infection. BNT162b2 booster doses have been proven to be protective against severe disease and mortality, yet if reducing transmissibility and achieving herd immunity is what we are striving for, a different vaccination ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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