Challenges for vaccination in the elderly

Abstract

The increased susceptibility of the elderly to infection presents a major challenge to public health services. An aging immune system is well documented as the cause of increased infection rates in elderly people. Such immunosenescence is multi-factorial and incompletely understood. Immunosenescent changes include malfunctioning of innate immune system cellular receptors; involution of the thymus, with consequent reduction of the naïve T cell population; alteration of the T cell population composition; modified phenotypes of individual T cells; and replicative senescence of memory cells expressing naïve markers. Unfortunately, immunosenescence also renders vaccination less effective in the elderly. It is therefore important that the vaccines used against common but preventable diseases, such as influenza, are specifically enhanced to overcome the reduced immune responsiveness of this vulnerable population.

Thymopoiesis in elderly human is associated with systemic inflammatory status

“…Among the clinical consequences of the immunosenescence are an increase in the frequency of infectious diseases (and, possibly, an increase in cancer and autoimmune diseases) (Yoshikawa 2000;Strindhall et al 2007) and poor response to vaccines (Gruver et al 2007). The loss of peripheral blood naive T cells is the bestknown effect of immunosenescence and the absence of response to vaccines has been ascribed, at least in part, to this decline (Aspinall et al 2007;Gruver et al 2007). The peripheral naive T-cell pool is maintained, preferably, by thymic lymphopoiesis as well as by the homeostatic mechanisms that account for the peripheral expansion (Cambier 2005;Cicin-Sain et al 2007).…”

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

“…The problem is compounded by the reduced efficacy of seasonal influenza vaccines in the elderly, with estimated vaccine efficacy at 17–53%, compared with 70–90% in young adults 4 . This is mainly due to immunosenescence that compromises the ability to mount protective immune responses to vaccine antigens 3 , 4 , 5 . In addition, antigenic drift during the influenza season further reduces the efficacy of seasonal influenza vaccination in the most vulnerable populations, such as the elderly 6 .…”

“…In addition, antigenic drift during the influenza season further reduces the efficacy of seasonal influenza vaccination in the most vulnerable populations, such as the elderly 6 . The small changes in the haemagglutinin (HA) and neuraminidase (NA) genes that occur during antigenic drift are sufficient to hinder the match between the strains recommended by WHO for inclusion in the vaccine formulation and circulating viruses, which can, in turn, reduce the immune response to vaccination 3 , 4 , 5 . In elderly subjects, seroprotection rates as low as 20% against drifted viruses have been reported, often failing to meet Committee for Medicinal Products for Human Use (CHMP) criteria for seroprotection and seroconversion against drifted strains 7 , 8 , 9 , 10 , 11 .…”

Ageing, immunity and influenza: a role for probiotics?

“…Since a diverse T cell repertoire is essential for an effective immune response to new infections and to immunisation, older individuals face a significant challenge in dealing with both (15,16) . It is well established that ageing is associated with an increased susceptibility to infections (17) and that vaccines are considerably less effective in older people (16,18,19) , presenting a major public health challenge. Prolonged exposure to TNF, and perhaps other inflammatory cytokines, promotes immunosenescence; indeed young individuals with chronic inflammatory disease exhibit premature immunosenescence, telomere shortening and reduced thymic output (reviewed in (14) ).…”

“…As a result, there is greater morbidity resulting from respiratory infections in elderly individuals, and influenza is a major cause of death in the over 65s (21,22) . The efficacy of influenza vaccination is also significantly impaired by ageing; it is estimated that influenza vaccination protects only 17-53% of elderly individuals compared with 70-90% of young (19,23) . A direct relationship between poor vaccination and immunosenescence is illustrated by the fact that loss of CD28 (an important co-stimulatory molecule on T cells) is one of the most well-recognised features of immunosenescence and is correlated with a poor response to vaccination (24)(25)(26) .…”