Adaptive immune responses in adults of different ages who received 2 doses of BNT162b2 mRNA vaccine

In a recently published study in aging in naturethe researchers examined the correlation between immune senescence and poor vaccination outcomes against coronavirus disease 2019 (COVID-19) in older adults.

background

A COVID-19 hospitalization and the associated fatal outcome can be avoided by vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have shown that vaccines become less effective in older people, affecting their overall health.

However, information is lacking on how and to what extent age-related immunological defects are responsible for the diminishing vaccination response observed in elderly people vaccinated with the SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine.

About the study

In the present study, the researchers evaluated the adaptive immunological responses of subjects aged 22 to 99 who received two doses of the BNT162b2 mRNA vaccine.

For this study, 66 participants were enrolled and blood samples were taken 42 to 81 days after the first vaccination. Eligible individuals had no history of SARS-CoV-2 infection or related symptoms. SARS-CoV-2 infected patients with polymerase chain reaction (PCR) confirmation were also included. The study participants were also tested for SARS-CoV-2 neutralizing antibodies (VN).

We examined whether age also affects the strength and caliber of SARS-CoV-2 specific T cell responses. The team used an ex vivo interferon gamma (IFN-ɣ) enzyme-linked immunospot assay (ELISpot) to detect peripheral blood mononuclear cells (PBMCs) with overlapping peptides via the SARS-CoV-2 spike (S )-1 and S2 subunits.

Taking into account surface expression of CC chemokine receptor type 7 (CCR7) and CD45RA, the team classified the CD4+ and CD8+ T cells into four differentiation subgroups: naïve, central memory T (TCM), effector memory T (TEM), and effector Memory CD45RA+ T (TEMRA). The proportions of cells were associated with the frequency of S-specific T cells as determined by IFN-ELISpot.

Results

Compared to young and middle-aged individuals, the team found an age-related decline in neutralizing antibodies from vaccination at significantly lower titers in older adults. As a result of age-related changes affecting B cells, reduced activation of SARS-CoV-2-specific antibodies and MBCs has also been observed in older individuals. SARS-CoV-2-specific T cells can protect against the severity of COVID-19 in the absence of healing antibodies, which may be crucial for the elderly who do not produce VN antibodies.

Age and the Charlson Comorbidity Index were associated with a decrease in the frequency of S-specific T lymphocytes. There was no correlation between the time elapsed since the last vaccination and the extent of the S-specific response. The overall S-specific T-cell response was significantly lower in those over 66 years of age compared to the younger group, and to a lesser extent between middle-aged and older individuals. As a result, vaccinates of 66 or more had a greater percentage of non-responders than those in the other two age groups. The young and middle-aged showed no discernible difference, suggesting that older adults were most affected by the weakening of the vaccine-induced immune response.

As a result of spike peptide stimulation, there was also an age-dependent decline in CD4+ T cells producing interleukin (IL)-2+IFN-ɣ+, TNF-⍺+ IFN-ɣ+ and IL-2+ TNF-⍺+, with older people showing a striking decline in these polyfunctional T cells compared to the two younger age groups.

The team also found that middle-aged people have fewer polyfunctional CD4+ T cells than young adults. In contrast, infection with SARS-CoV-2 resulted in polyfunctional CD4+ T cells across all age groups, albeit at slightly lower levels in older individuals.

A reduction in naïve T cells and an increase in terminally developed T cells were also observed. Levels of S-specific IFN spot-forming cells (SFCs) decreased along with age-related declines in CD4+ and CD8+ naïve T cells. When the IFN-alpha response to non-naïve T cells was assessed by intracellular cytokine staining (ICS), comparable results were found.

Comparison of data from different age groups showed an age-dependent relationship between CD4+ and CD8+ naïve T cells and the S-specific T cell response. Particularly in people over 66 years of age, the loss of naïve CD8+ T cells was inversely linked to the post-vaccination induced T cell response. Notably, higher levels of CD4+ TCM and CD8+ TEMRA in the elderly were inversely associated with the vaccine-induced T-cell response, although no correlation was found with the CD8+ TEM and TCM subsets and CD4+ TEMRA and TEM.

Conclusion

Overall, study results showed that adaptive immune responses to BNT162b2 immunization generally declined with age. Because some of the factors examined were correlated with age, the association between aging and redistribution of subsets of T cell differentiation and inadequate T and B cell immunological responses to vaccination does not imply a direct causal relationship.