Antibody response after first and second BNT162b2 vaccination to predict the need for subsequent injections in nursing home residents

Abstract

We explored antibody response after first and second BNT162b2 vaccinations, to predict the need for subsequent injections in nursing home (NH) residents. 369 NH residents were tested for IgG against SARS-CoV-2 Receptor-Binding Domain (RBD-IgG) and nucleoprotein-IgG (SARS-CoV-2 IgG II Quant and SARS-CoV-2 IgG Alinity assays, Abbott Diagnostics). In NH residents with prior SARS-CoV-2 infection, the first dose elicited high RBD-IgG levels (≥ 4160 AU/mL) in 99/129 cases (76.9%), with no additional antibody gain after the second dose in 74 cases (74.7%). However, a low RBD-IgG level (< 1050 AU/mL) was observed in 28 (21.7%) residents. The persistence of nucleoprotein-IgG and a longer interval between infection and the first dose were associated with a higher RBD-IgG response (p < 0.0001 and p = 0.0013, respectively). RBD-IgG below 50 AU/mL after the first dose predicted failure to reach the antibody concentration associated with a neutralizing effect after the second dose (≥ 1050 AU/mL). The BNT162b2 vaccine elicited a strong humoral response after the first dose in a majority of NH residents with prior SARS-CoV-2 infection. However, about one quarter of these residents require a second injection. Consideration should be given to immunological monitoring in NH residents to optimize the vaccine response in this vulnerable population.

Figure 1

RBD-IgG vaccine response after first and second doses. (A) Individual changes in RBD-IgG levels after first and second doses in NH residents with and without prior SARS-CoV-2 infection. RBD-IgG between first and second doses in NH residents with (red) and without (green) prior SARS-CoV-2 infection. (B) ROCs to evaluate RBD-IgG levels after the first dose, predictive of the lack of additional gain in RBD-IgG following the second dose in NH residents with prior SARS-CoV-2 infection; for a RBD-IgG level > 12,079 AU/mL: positive predictive value (PPV): 76.7%, negative predictive value (NPV): 54.5%, sensitivity: 92.5%; specificity: 66.7%. (C) ROC evaluating RBD-IgG levels after the first dose, predictive of the failure to reach a significant RBD-IgG level after the second dose (< 1050 AU/mL) in NH residents without prior SARS-CoV-2 infection; RBD-IgG < 50 AU/mL: PPV: 53.5%; NPV: 89.2%; sensitivity: 77.6%; specificity: 73.3%. (D) ROC to evaluate the RBD-IgG level after the first dose, predictive of a high RBD-IgG level following the second dose (≥ 4160 AU/mL) in NH residents without prior SARS-CoV-2 infection; RBD-IgG > 228 AU/mL: PPV: 58.8%; NPV: 85.0%; sensitivity: 82.8%; specificity: 62.7%.

Figure 2

RBD-IgG levels among participants with or without prior SARS-CoV-2 infection. (A) Distribution of RBD-IgG levels in the entire population of participants 3 weeks after the first dose. (B) ROC evaluating the performance of RBD-IgG levels after the first dose, as a marker of prior SARS-CoV-2 infection; RBD-IgG > 4160 AU/mL: PPV: 98.0%; NPV: 89.8%; sensitivity: 76.7%; specificity 99.3%. (D) Distribution of RBD-IgG levels in the entire population of participants 6 weeks after the first dose. (C) ROC evaluating the performance of RBD-IgG levels after the second dose, as a marker of prior SARS-CoV-2 infection; RBD-IgG > 15,000 AU/mL: PPV: 93.3%; NPV: 85.3%; sensitivity: 65.1%; specificity: 97.8%.

Figure 3

Impact of the interval between infection and vaccination and nucleoprotein-IgG status on RBD-IgG levels after the first dose. (A) RBD-IgG level according to the interval between SARS-CoV-2 infection and first dose. (B) RBD-IgG level according to the interval between SARS-CoV-2 infection and second dose. (C) Nucleoprotein-IgG S/CO value according to interval since SARS-CoV-2 infection. (D) ROC evaluating the performance of RBD-IgG S/CO index to predict a high RBD-IgG level after the first dose; RBD-IgG S/CO index > 0.5: PPV: 90.9%; NPV: 96.3%; sensitivity: 90.9% ; specificity: 70.0%). (E) RBD-IgG level after the first dose according to nucleoprotein-IgG status and interval since SARS-CoV-2 infection.

Figure 4

RBD-IgG levels after SARS-CoV-2 infection and relationship to vaccine response. (A) RBD-IgG level in response to natural immunization, 4–8 weeks (26 NH residents) and 7–8 months (n = 71 NH residents) after SARS-CoV-2 infection. (B) Individual changes in RBD-IgG levels after the first dose, in NH residents tested 7–8 months after SARS-CoV-2 infection. (C) Follow-up of RBD-IgG levels in NH residents tested after natural immunization and vaccination; black line indicates the mean RBD-IgG level.