Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities

Abstract

Background: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine.

Methods: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group.

Results: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels.

Conclusions: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.

Keywords: BNT162b2 vaccine; SARS-CoV-2; humoral immune response; long-term care facilities; nursing homes; older people.

Figure 1

Comparison of humoral response and neutralising activity between uninfected and infected individuals 3 months after BNT162b2 mRNA COVID-19 vaccine. (A) Levels of SARS-CoV-2-specific immunoglobulins (IgG, IgA and IgM) against S2 + RBD proteins quantified in plasma from uninfected and infected older participants by ELISA. (B) SARS-CoV-2-specific IgG antibody levels (against S2 + RBD proteins) after vaccination across ages in infected and uninfected participants. (C) Neutralising activity against WH1 virus before and after 3 months of vaccine administration in infected and uninfected older residents of LTCF. (D) Neutralising activity against WH1 after vaccination across ages in infected and uninfected participants. (E) Correlation of neutralising activity after vaccination with age in infected and uninfected participants. Correlation coefficient and P-values were obtained from Spearman correlation. (F) Ratio of plasma neutralisation titre per total SARS-CoV-2-specific IgG antibodies in younger and older participants, sub-grouped by previous SARS-CoV-2 infection history. Median values are indicated; P-values were obtained from Mann–Whitney test for comparison between groups A, B, C, D and F), Wilcoxon test for paired tests ( C) and Kruskal–Wallis test for comparison between age ranges for infected and uninfected groups (B and D). In all panels, uninfected and infected participants at vaccination are indicated in turquoise and purple, respectively.

Figure 2

Neutralising activity against B.1.617.2/Delta variant between uninfected and infected participants 3 months after BNT162b2 mRNA Covid-19 vaccine. (A) Comparison of plasma neutralising activity against WH1 and B.1.617.2/Delta variant in uninfected and infected older participants after vaccination. (B) Neutralising activity against Delta variant after vaccination across ages in infected and uninfected, younger and older participants, sub-grouped by previous SARS-CoV-2 infection history. (C) Fold change ratios between neutralisation titres against Delta variant and WH1 (reference spike) virus in infected and uninfected participants, sub-grouped by age (<65 years and ≥ 65 years). Median values are indicated. P-values were obtained from Mann–Whitney test for comparison between groups (all panels), Wilcoxon test for paired tests (A and C) and Kruskal–Wallis test for each group (B). In all panels, uninfected and infected participants at vaccination are indicated in turquoise and purple, respectively.