Humoral and Cellular Responses to COVID-19 Vaccination Indicate the Need for Post-Vaccination Testing in Frail Population

Abstract

Despite the high efficacy of the BNT162b2 vaccine in the general population, data on its immunogenicity among frail elderly individuals are limited. Recently, levels of anti-SARS-CoV-2 spike IgG antibodies and serum neutralization titers were confirmed as good immune markers of protection against the virus, with evidence showing a reverse correlation between these two parameters and susceptibility to infection. Here we analyzed sera from 138 nursing home residents (median age of 88.9 years) and 312 nursing home staff (median age of 50.7 years) to determine the humoral response to two doses of the BNT162b2 vaccine, and found markedly decreased serum anti-spike antibody levels and neutralization titers in the nursing home resident (NHR) group, with over 11% non-responders compared to only 1.3% among the controls. Moreover, three months post-vaccination, a significant decrease in antibody titers was observed in COVID-19-naive nursing home residents. Subsequent flow cytometry and interferon gamma secretion analyses indicated that antibody non-responders among NHRs also failed to mount cellular responses. The presented data emphasize that additional measures are needed in the population of frail elderly individuals. Given the high proportion of non-responders among NHRs, continued monitoring should be considered in this group.

Keywords: SARS-CoV-2; antibodies; cellular immunity; nursing home; vaccination.

Figure 1

Nursing home residents showed impaired antibody response to two doses of BNT162b2 vaccine. (A) Anti-S1 IgG levels at week 2 post-vaccination with the second dose in NHS (n = 312) and NHRs (n = 138). (B) Data as in (A) shown in respect to the pre-vaccination anti-SARS-CoV-2 serostatus. (C,D) Ability of serum collected from NHS and NHRs two weeks post-vaccination to neutralize SARS-CoV-2 pseudovirus. * p-value = 0.049, ** p-value = 0.0014, **** p-value < 0.0001, ns-not significant. Dotted horizontal lines show manufacturer’s determined cutoff level and grey-zone values.

Figure 2

Infection status predicted antibody levels 3 months post-vaccination. (A) Evolution of anti-S1 antibody levels in NHRs (n = 20) measured at the moment of first vaccine dose administration, and at 2 weeks and 3 months after the second dose. (B) Pseudovirus neutralization measured two weeks after the first vaccine dose administration and 3 months after the second dose.

Figure 3

SARS-CoV-2 pre-infection prevented anti-S1 IgG decline. (A) Percentage change in anti-S1 IgG levels from two weeks to 3 months after administration of the second dose of vaccine in infected (n = 7) and non-infected (n = 4) NHR responders. (B) Ability of NHR serum to neutralize pseudovirus three months after the second dose of vaccine administration. * p-value = 0.02, ** p-value = 0.006.

Figure 4

There were no SARS-CoV-2-specific cellular responses in NHRs lacking antibody response to vaccination. (A) Dot plots demonstrate typical CD4+ T-cell response to stimulation with a pool of spike peptides in NHR non-responders (left column) and responders (right column) as determined by anti-S1 IgG ELISA. Graphs indicate differences in the percentage of TNFα+ or CD69+/CD40L+, CD4+ T cells. (B) Graph indicates differences in IFNγ secretion from NHR (n = 20) PBMCs following 22 h stimulation with SARS-CoV-2 spike peptide pool. * p-value = 0.04, **** p-value < 0.0001, ns-not significant.