Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Abstract

BackgroundImmune protection following either vaccination or infection with SARS-CoV-2 decreases over time.ObjectiveTo determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals.MethodsAntibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine.ResultsA total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection.ConclusionsThis study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.FundingThis research was internally funded by Leumit Health Services (LHS) and was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research.The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Impact statementLarge scale study display the kinetics of SARS-CoV-2 IgG antibodies present in individuals vaccinated with two doses of mRNA vaccine vs. unvaccinated patients who had recovered from the disease: initial levels of antibody are much higher in vaccinated patients, but decrease faster.

Waning of IgG, total and neutralizing antibodies 6 months post-vaccination with BNT162b2 in healthcare workers

“…12,153 AU/mL). 31 These data are con rmed by our study, especially in the seronegative cohort. The higher mean titers observed in our study may be related to the lower age of our cohort compared to the one of Israel et al (42.0 versus 56.5 years), which has been reported as a confounding factor for antibody response.…”

“…10.8% at 9 months). 31 In our study, no participant had IgG or total antibodies titers below the manufacturers' threshold. In contrast to Israel et al, we also enrolled subjects categorized as seropositive before the rst vaccine injection and observed an IgG decrease of 79.4% in this group (Fig.…”

“…As reported elsewhere, the vaccination with BNT162b2 elicited much higher total antibodies and IgG titers compared to ones obtained in convalescent patients. 12,26,31 In our model, the T MAX for total antibodies and IgG was reached at a similar timeframe in the two cohorts. The model also predicts a drop of IgG below the positivity threshold (i.e.…”

“…32,33 Moreover, the antibody decline was also higher compared to convalescent patients where a drop of 4 to 7% every month has been reported compared to drop observed in our vaccinated subjects. 31,34 Finally, the proportion of vaccinees below the threshold of 50 AU/mL was higher (i.e. 16.1% at 6 months) compared to the one in convalescent subjects (i.e.…”

The longitudinal kinetics of antibodies in COVID-19 recovered patients over 14 months

“…Stable maintenance of antibody reservoirs can provide a mechanism to help mitigate subsequent infections. In the context COVID-19, the importance of the antibody reservoir is further highlighted by evidence of the temporal decay of the serological memory as observed in COVID-19 recovered patients and recent data suggesting that antibody levels wane in vaccinated individuals 30,31 . Additionally, in a recent report by Israelow et al 32 it was suggested that immune protection is largely mediated by antibody response and not cellular immunity highlighting the protective capacity of antibodies elicited by both natural infection and vaccination.…”