Third COVID-19 vaccine dose boosts neutralizing antibodies in poor responders
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Abstract
Background
While evaluating COVID-19 vaccine responses using a rapid neutralizing antibody (NAb) test, we observed that 25% of mRNA vaccine recipients did not neutralize >50%. We termed this group “vaccine poor responders” (VPRs). The objective of this study was to determine if individuals who neutralized <50% would remain VPRs, or if a third dose would elicit high levels of NAbs.
Methods
269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines were evaluated. NAb levels were measured: (i) 2–4 weeks after a second vaccine dose, (ii) 2–4 months after the second dose, (iii) within 1–2 weeks prior to a third dose and (iv) 2–4 weeks after a third mRNA vaccine dose.
Results
Analysis of vaccine recipients reveals that 25% did not neutralize above 50% (Median neutralization = 21%, titers <1:80) within a month after their second dose. Twenty-three of these VPRs obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1–8 months (average = 5 months) after their second dose. Within a month after their third dose, VPRs show an average 5.4-fold increase in NAb levels (range: 46–99%).
Conclusions
The results suggest that VPRs are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose. Although it is not known what levels of NAbs protect from infection or disease, those in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, and potential transmission.
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SciScore for 10.1101/2021.11.30.21266716: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Study Design and Participant Enrollment: Male and female adults ranging in age from 18-80 years old were recruited with informed consent to measure their NAb levels after vaccination with either BNT162b2 or mRNA1273.
IRB: The study was approved by the internal review board at Arizona State University.Sex as a biological variable Study Design and Participant Enrollment: Male and female adults ranging in age from 18-80 years old were recruited with informed consent to measure their NAb levels after vaccination with either BNT162b2 or mRNA1273. Randomization not detected. Blinding not detected. Power Analysis Post-hoc power analysis was computed using G*Power 3.1 software(15). Table 2: …
SciScore for 10.1101/2021.11.30.21266716: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Study Design and Participant Enrollment: Male and female adults ranging in age from 18-80 years old were recruited with informed consent to measure their NAb levels after vaccination with either BNT162b2 or mRNA1273.
IRB: The study was approved by the internal review board at Arizona State University.Sex as a biological variable Study Design and Participant Enrollment: Male and female adults ranging in age from 18-80 years old were recruited with informed consent to measure their NAb levels after vaccination with either BNT162b2 or mRNA1273. Randomization not detected. Blinding not detected. Power Analysis Post-hoc power analysis was computed using G*Power 3.1 software(15). Table 2: Resources
Software and Algorithms Sentences Resources Statistical Analyses: Levene’s test was used to assess homoscedasticity between groups prior to significance testing (IBM SPSS Statistics for Macintosh, Version 26.0; Armonk, NY). SPSSsuggested: (SPSS, RRID:SCR_002865)To account for unequal variances resulting from unequal sample sizes, Welch’s t-test with Benjamini-Hochberg false discovery rate (FDR) correction was performed using Microsoft Excel (Version 16.55; Redmond, WA) to evaluate significant differences in mean neutralisation between BNT162b2 (n = 180) and mRNA-1273 (n = 89) 2-4 weeks post-2nd dose. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Post-hoc power analysis was computed using G*Power 3.1 software(15). G*Powersuggested: (G*Power, RRID:SCR_013726)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:Limitations of the study: This study has several limitations. First, it is still unknown what levels of neutralising antibodies correlate with protection against infection and potential disease. It is possible, but unlikely, that NAb levels as low as 20% could protect against infection(6). Second, although the N-terminal domain of spike protein also been shown to neutralise SARS-CoV-2, it is currently characterised as a minor component of neutralising antibodies(7,31) and our test does not detect them. Although we measured NAb levels for twice as many BNT162b2 vaccine recipients as mRNA-1273 recipients, we examined homogeneity of variance using Levene’s test and, upon confirming unequal variances, assumed Welch’s t-test as a conservative and robust alternative to parametric comparisons of means. Importantly, potential for type I error was mitigated using FDR-adjustment of calculated significance, and Cohen’s d showed appreciable effect size between groups. Moreover, post-hoc power analysis showed exceptional sensitivity and low chance of type II error, further supporting the significantly lower percent neutralisation observed in Pfizer recipients 2-4 weeks post-2nd dose.
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.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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