Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: A prospective observational study in older adults aged from 68 to 98 years

Abstract

Background: The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents.

Methods: In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered).

Findings: 106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p < 0.0001) and a mild transient increase of specific T cells. Before the booster dose, Delta neutralization was detected in 19% (n = 8/43) and 88% (n = 37/42) of COVID-19 naive and COVID-19 recovered subjects, respectively. Three months after the booster dose, all NH residents developed and maintained a higher Delta neutralization (p < 0·0001). Before the booster dose, Omicron neutralization was detected in 5% (n = 2/43) and 55% (n = 23/42) of COVID-19 naive and COVID-19 recovered subjects, respectively, and three months after, in 84% and 95%, respectively. Neutralizing titers to Omicron were lower than to Delta in both groups with a 35-fold reduction compared to Delta.

Interpretation: The booster dose restores high neutralization titers against Delta in all NH residents, and at a lower level against Omicron in a large majority of participants. Future studies are warranted to assess if repeated BNT162b2 booster doses or new specific vaccines might be considered for protecting such fragile patients against Omicron and/or future SARS-CoV-2 variants.

Funding: French government through the Programme Investissement d'Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE) and the Label of COVID-19 National Research Priority (National Steering Committee on Therapeutic Trials and Other COVID-19 Research, CAPNET).

Keywords: BNT162b2 vaccine; Boost; Delta; Older people; Omicron; SARS-CoV-2; immunogenicity.

Figure 1

Anti-S1 antibody levels before, 1-month and 3-month after booster BNT162b mRNA vaccine dose in NH residents. Individual values and median [interquartile range (IQR)] are shown. (A) Anti-S1 IgG levels in NH residents without (naive, blue) or with (recovered, red) prior COVID-19 before initial vaccination according to time (in months), from before initial vaccination (Dose 1, D1; Dose 2, D2; time interval between D1-D2: 21 to 28 days), to 3-month post booster vaccine dose. Mann-Whitney U test was performed to compare naive and recovered residents. ****p-values < 0·0001 (B) Comparison of antibody levels before (pre-boost) and at 1- and 3-month post-booster vaccine dose in COVID-19 naive NH residents (blue) and in COVID-19 recovered residents (red). No statistical comparison was performed because a large part of antibody levels was greater than the upper limit of detection.

Figure 2

S1 specific reactive T cells before, 1-month and 3-month after booster BNT162b mRNA vaccine dose in NH residents. Individual values and median [interquartile range (IQR)] are shown. (A) S1 specific reactive T cells in NH residents without (naive, blue) or with (recovered, red) prior COVID-19 before initial vaccination (Dose 1, D1; Dose 2, D2; time interval between D1-D2: 21 to 28 days), according to time (in months), from before initial vaccination to 3-month post booster vaccine dose. Mann-Whitney U test was performed to compare naive and recovered residents. (B) Comparison of S1 reactive T cells before (pre-boost) and 1- and 3-month post-booster vaccine dose in COVID-19 naive NH residents (blue) and in COVID-19 recovered residents (red). Wilcoxon signed rank test was used for within-subjects comparisons. ****p-value < 0·0001, ** p-value < 0·01, ns, not significant

Figure 3

Neutralization of the Delta and Omicron variants before and 3 months after booster BNT162b mRNA vaccine dose in NH residents. Individual values, geometric mean neutralization titers (GMNT) and 95% confidence intervals are shown. Percentages and pie charts show the proportion of participants within each group that had detectable neutralization against the indicated variant. Serum neutralization titers of live B.1.617.2 (Delta, left) and B.1.1.529 (Omicron, right) SARS-CoV-2 strains determined for NH residents without (naive, blue) or with (recovered, red) COVID-19 before initial vaccination. Wilcoxon signed rank test was used for within-subjects comparisons. Mann-Whitney U test was performed to compare naive and recovered residents at 3 months. *p-values < 0·05; ****p-values < 0·0001; ns, not significant.

Figure 4

Fold-decrease in neutralization titers of Omicron relative to Delta 3 months after booster BNT162b mRNA vaccine dose in NH residents. Individual values and fold-decrease in geometric mean neutralization titers (GMNT) of Omicron relative to Delta in NH residents without (naive, blue) or with (recovered, red) COVID-19 before initial vaccination is shown as a number with ‘‘x’’ symbol. Patients without detectable antibodies were not included in the GMNT reduction calculation. Wilcoxon signed rank test was used for within-subjects comparisons in titers found with Delta and Omicron variants 3 months after the boost vaccine dose. ****p-values < 0·0001.