Efficacy and Safety of COVID-19 Vaccines in Older People

Roy L. Soiza; Chiara Scicluna; Emma C. Thomson


Age Ageing. 2021;50(2):279-283. 

In This Article

Generalisability to Older People With Frailty

The efficacy of vaccines in general in older people is not well studied.[11] Typically, surrogate markers of efficacy measures are antibody titres, antibody isotypes and the ability of the immune system to neutralise pathogens. Immunosenescence is a broad term used to encompass declining immunity with age, encompassing both quantitative and qualitative aspects of immune system responses that are likely to impact on the observed safety and efficacy profile of vaccines. With advancing age there is a reduction in naive T cells available to respond to a vaccine. The normal ratio of CD4:CD8 cells becomes much higher in older age, due to a significant decrease in CD8 T cells. Ageing also brings a loss of T cell receptor diversity in both CD8 and CD4 cells, and overall reduced T cell survival. Qualitative changes include the favoured production of short-lived effector T cells over memory precursor cells, resulting in an impaired response of T follicular helper cells to vaccination. Naive T cells are also genetically and phenotypically more alike to central memory T cells than they are in a younger population, impacting their plasticity.[11] B cell numbers remain more consistent with age but, due to a reduced expression of select proteins in old age, fewer functional antibodies are produced.[12] Theoretically therefore, vaccines are likely to be somewhat less effective in older people. Moreover, the relative importance of cellular aspects of the immune response in COVD-19 is unclear, even more so in older people, so antibody levels may not be adequate surrogates for immunity.[13] The impact of immunosenescence on vaccine safety is even more uncertain. Though the risk of serious adverse events mediated by over-activation of the immune system is theoretically lower, this may be offset by increased predisposition to adverse events overall, as this is the hallmark of frailty.