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. 2021 Sep 30;13(10):1972. doi: 10.3390/v13101972

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Functional neutralization assays are better predictors of the humoral immune response to COVID-19 mRNA-based vaccinations. Samples are described as the 1st or 2nd samples after 1st or 2nd vaccine dose (1 S-P1 st-vd, 1 S-P2 nd-vd or 2 S-P2 nd-vd) and the mean time of samples collection is shown. Panels (A,B) show the total antibody and IgG titers, respectively, after full vaccination with two vaccine doses. Antibody levels and titers significantly decline in both groups in a second sample collected after the second vaccine (average of 60.3 and 100.5 days after the first vaccine dose for the unexposed and pre-exposed groups, respectively). Despite the difference in sampling time between the two groups, there were no significant differences in the levels of antibodies or titers between groups in the 2 S-P2 nd-vd. Panel (C) shows antibody-blocking capabilities measured by a surrogate viral neutralization assay (sVNT). Highly relevant is the finding that the blocking baseline activity of the pre-exposed individuals is significantly higher than the basely blocking activity induced by the first vaccine dose in unexposed individuals. In addition, two vaccine doses were necessary in the unexposed cohort to induce same percentage of neutralization achieved by just the first dose in the pre-exposed group. The magnitude of neutralization remained at similar levels until the last time point evaluated in both groups, confirming that the surrogate neutralization test is more suitable to determine the efficacy of the humoral immune response to the vaccine. The threshold for the total antibodies was 0.312. The threshold for IgG titers was 1:100 and for the blocking activity was 30%. Statistical significance was determined by one-way ANOVA multiple comparisons test or unpaired t-test to test for an increase or decrease among samples. p < 0.05 was considered significant. The black arrows indicate the moment of vaccine administration related to the timing of sample collection. Healthy vaccinated (n = 21); pre-exposed vaccinated (n = 10).