If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
To measure the antibody decay after 2 BNT162b2 doses and the antibody response after a third vaccine dose administered 6 months after the second one in nursing home residents with and without prior COVID-19.
Setting and Participants
Four hundred-eighteen residents from 18 nursing homes.
Blood receptor-binding domain (RBD)-IgG (IgG II Quant assay, Abbott Diagnostics; upper limit: 5680 BAU) and nucleocapsid-IgG (Abbott Alinity) were measured 21‒28 days after the second BNT162b2 dose, as well as 1‒3 days before and 21‒28 days after the third vaccine dose. RBD-IgG levels of ≥592 BAU/mL were considered as high antibody response. Residents with prior positive quantitative reverse transcription polymerase chain reaction on a nasopharyngeal swab or with N-IgG levels above 0.8 S/CO were considered as prior COVID-19 residents.
In prior COVID-19 residents (n = 122), RBD-IgG median levels decreased by 82% in 167 days on average. In the same period, the number of residents with a high antibody response decreased from 88.5% to 54.9% (P < .0001) and increased to 97.5% after the third vaccine dose (P = .02 vs the first measure). In residents without prior COVID-19 (n = 296), RBD-IgG median levels decreased by 89% in 171 days on average. The number of residents with a high antibody response decreased from 29.4% to 1.7% (P < .0001) and increased to 88.4% after the third vaccine dose (P < .0001 vs the first measure).
Conclusions and Implications
The strong and rapid decay of RBD-IgG levels after the second BNT162b2 dose in all residents and the high antibody response after the third dose validate the recommendation of a third vaccine dose in residents less than 6 months after the second dose, prioritizing residents without prior COVID-19. The slope of RBD-IgG decay after the third BNT162b2 dose and the protection level against SARS-CoV-2 B.1.1.529 (omicron) and other variants of concern provided by the high post-boost vaccination RBD-IgG response require further investigation in residents.
has been shown to be lower than that observed in health care professionals. In addition, outbreaks of the SARS-CoV-2 variants [B.1.1. 4-7 (alpha) and B.1.617.2 (delta)] have been reported in NHs less than 6 months after the full BNT162b2 vaccination of most residents.
The low humoral response observed after 2 BNT162b2 doses, associated with reduced vaccine protection some months after the second vaccine dose, has led to recommendations in the US and in other countries such as France of an additional vaccine dose at least 5 months after the second vaccine dose in persons moderately or severely immunocompromised.
The 6-month postvaccine antibody decay after the second vaccine dose and the antibody response to the third dose have not been quantified in the same NH residents, which does not enable the comparison of the antibody response after 2 and 3 BNT162b2 doses.
We compared IgG levels against the SARS-CoV-2 receptor-binding domain (RBD)-IgG) (1) after 2 doses of BNT162b2, (2) just before the third vaccine dose, and (3) after the third dose. We distinguished those with and without prior COVID-19.
Since March 2019, around 6000 residents from 122 nursing homes are being prospectively followed in the Montpellier area (French Occitanie region). All residents, with or without prior COVID-19 (outbreaks of wild type SARS-CoV-2 between March 2020 and February 2021; of SARS-CoV-2 B.1.1.7 between February 2021 and October 2021; of B.1.617.2 between July 2021 and October 2021) were offered 2 vaccine doses in January‒February 2021, and a third dose 6 months later. A follow-up of postvaccine antibody response was proposed in residents from 15 nursing homes having faced a COVID-19 outbreak in 2020. Blood testing was performed 21‒28 days after the second vaccine dose, as well as 1‒3 days before and 21‒28 days after the third dose, to assess RBD-IgG (IgG II Quant assay, Abbott Diagnostics; upper limit: 5680 BAU) and nucleocapsid-IgG (Abbott Alinity). RBD-IgG levels of <149 BAU/mL or ≥592 BAU/mL were considered as low or high responses, respectively.
Residents with a history of positive quantitative reverse transcription polymerase chain reaction on a nasopharyngeal swab or with N-IgG levels above 0.8 S/CO were considered as prior COVID-19 residents. All participants (or their legal representative) provided informed consent. The study was approved by our University Hospital institutional review board. RBD-IgG levels were compared by using the Friedman and Cochran tests, and the multinomial mixed model for repeated measures. The statistical significance threshold was set at 5%. Analyses were performed using the SAS Enterprise Guide, v 7.3 (SAS Institute Inc).
The characteristics of the residents included in the 15 nursing homes are shown in Table 1. Of the 418 studied residents, 296 had no previous COVID-19 infection (mean age 88 ± 8 years, 74% women) and 122 had prior COVID-19 (88.6 ± 8 years, 81% women). The mean lapse of time between the first and the second RBD-IgG measures were 171 ± 11 and 167 ± 11 days, respectively.
Table 1Demographic Characteristics of the Residents Studied in 15 NHs
In prior COVID-19 residents, RBD-IgG median levels decreased by 82% between the first and second measures (4318 BAU/mL to 773 BAU/mL), and the number of residents with a high antibody response decreased from 88.5% to 54.9% (P < .0001). After the third dose, RBD-IgG median levels increased significantly (to 3596 BAU/mL), and the number of residents with a high RBD-IgG level was higher after the third and after the second dose (97.5% vs 88.5%, respectively) (P = .02) (Table 2, Figure 1).
Table 2RBD-IgG Levels 4‒5 Weeks after the Second BNT162b2 Vaccine Dose (A), 1‒3 days before the Third Vaccine Dose (B), and 4‒5 Weeks after the Third Vaccine Dose (C) of Residents with (n = 122) or without (n = 296) Confirmed Prior COVID-19 Infection
In residents without prior COVID-19, RBD-IgG median levels between the first and second measures decreased by 89% (348 BAU/mL to 35 BAU/mL) and the number of residents with a high antibody response decreased from 29.4% to 1.7% (P < .0001). After the third vaccine dose, 88.4% of residents had a high antibody response vs 29.4% after the second dose, and 4.7% had a low antibody response vs 27.4% (P < .0001; Table 2, Figure 1).
This preliminary study shows that 6 months after the second BNT162b2 dose, 88.8% of residents without prior COVID-19 have an RBD-IgG level below 149 BAU and only 54.9% of those with prior COVID-19 have an RBD-IgG level above 592 BAU. The 82%‒89% decrease in RBD-IgG level observed in both groups in less than 6 months may partly explain the occurrence of outbreaks of the SARS-CoV-2 variants B.1.1. 4-7 and, more recently, of the Delta variant B.1.617.2 in NHs in which most of the residents had been vaccinated with 2 doses of the BNT162b2 vaccine.
This tends to validate, on an immunologic basis, the recommendation of a third BNT162b2 dose at least 5 months after the second one in NH residents. The RBD-IgG response after 3 vaccine doses is significantly higher than that observed after 2 doses and is excellent, largely above 592 BAU, in 97.5% of the residents with prior COVID-19 and in 88.4% of those without. Limitations of the study include the relatively small sample size, with a possible lack of representativeness and the lack of clinical data in residents with prior COVID-19. Whether the severity of the initial infection has impacted the antibody response to the vaccine cannot be analyzed in this study. One other limitation is the lack of neutralization assays. However, we used an automated quantitative assay to measure the RBD IgG level that correlates well with virus neutralization.
We did not assess T-cell contribution to vaccine-induced immunity. The present study focuses on antibodies and not on clinical disease. Even if associations have been shown between RBD-IgG levels and protection against SARS-CoV-2 in health care workers and NH residents,
Immune Assays Team; Moderna, Inc. Team; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team; United States Government (USG)/CoVPN Biostatistics Team Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.
whether the high level of RBD IgG found after a booster BNT162b2 dose in most residents is associated with high protection against COVID-19 remains to be determined.
Because the administration of a booster BNT162b2 dose as well as the vaccination of previously infected individuals generate an anti-B.1.1.529 neutralizing response, with titers 5- to 31-fold lower against Omicron than against Delta,
further studies are needed to assess whether the high RBD-IgG response found in most of the residents after the third vaccine dose will be sufficient to prevent SARS-CoV-2 B.1.1.529 in those with and without prior COVID-19 and, if so, for what duration.
Conclusions and Implications
The strong and rapid decay of RBD-IgG levels 6 months after the second BNT162b2 dose observed in most of the residents (with very low levels observed after the second dose in residents without prior COVID-19), as well as the high antibody response after the third dose in the residents (observed in the present study and in a recent unpublished study)
support, on an immunologic basis, the recommendation to offer a third vaccine dose in NH residents at least 5 months after the second dose, prioritizing those without prior COVID-19. Whether the slope of RBD-IgG decay after the third BNT162b2 dose will be similar to that found after the second vaccine dose, and whether the high RBD-IgG response found after the third vaccine dose will be associated with a high protection level against SARS-CoV-2 B.1.1.529 and other variants of concern require further investigation in NH residents.
The authors thank Jean Bousquet for the interpretation of data, Anna Bedbrook and Fabienne Portejoie for editorial assistance, Secours Infirmiers (Department of Geriatrics, Montpellier University Hospital), Florence Biblocque and Maxime Douville (admission office, Montpellier University Hospital) for material support, and the residents and staff members of the nursing homes involved in the study. None of these contributors received any compensation for their help in carrying out the study.
Ecological analysis of the decline in incidence rates of COVID-19 among nursing home residents associated with vaccination, United States, December 2020‒January 2021.