Vaccine effectiveness in older individuals: What has been learned from the influenza-vaccine experience

Abstract

a b s t r a c tVaccination policies in most high-income countries attempt to reduce the adverse impact of influenza targeting people aged at least 60 years. However, while it is widely believed that the current immunization strategy saves many lives, influenza infection still remains a severe burden in aged individuals leading to a wide debate on the exact magnitude of the benefit of vaccination in this population. The first aim of the present review is to examine how effective current influenza-vaccine strategies are in aged adults, by analysing which are the most important factors modulating the interpretation of study results in this population. Furthermore, consideration will be given to how immune factors influence the measurement of vaccine efficacy/effectiveness, where advancing age leads to deleterious changes in the adaptive immune system, resulting in less than optimal responses to infectious agents and vaccination. Finally this review concludes with possible strategies to improve the ability of the senescent immune system to respond to vaccination.

Seasonal Trivalent Inactivated Influenza Vaccine Protects against 1918 Spanish Influenza Virus Infection in Ferrets

“…For the current study, ferrets were vaccinated with TIV manufacturer-filled syringes designed for singledose administration. We chose not to use an adjuvant to vaccinate animals since the standard TIVs against influenza are mostly nonadjuvanted vaccines (21). It is worth noting that adjuvanted vaccines have demonstrated the ability, particularly in immunologically naïve animals, to significantly augment the cross-reactivity of antibodies induced by influenza virus vaccines (23,37).…”

“…For the inactivated trivalent influenza vaccine (hereinafter referred to as TIV), each 0.5-ml dose of TIV contains 15 g of influenza HA of each strain (45 g total) from three viral strains: two influenza A virus subtypes (H1N1 and H3N2) and one influenza B virus strain. The seasonal inactivated TIV is the most commonly administered influenza vaccine, and each year hundreds of millions of individuals are vaccinated worldwide (20,21).…”

Reversing T cell immunosenescence: why, who, and how

“…The downward trajectory of an individual's thymic output profile over time has been demonstrated previously by Kilpatrick et al (2008) and could be considered as part of longitudinal studies similar to the OCTA and NONA studies to investigate further the potential role of sj-TREC as predictive marker of aging (Wikby et al 2005;Strindhall et al 2007;Wikby et al 2008). Thus, whether predicting human phenotypes from genotypes is relevant both for personalized medicine and applying preventive strategies (Janssens and van Duijn 2008), additional clinical and translational studies at population, clinical, cellular, and molecular levels are still needed in order to elucidate the exact implications of the TREC values on the age-related senescence of the cell-mediated immune response (Lang et al 2011a). …”

“…In the older adults, there is a decrease both in the diversity and functional integrity of the CD4+ and CD8+ T cells subsets which contribute to a decreased ability to respond adequately to reinfection (Naylor et al 2005) and a poorer vaccine effectiveness (Lang et al 2011a). Age-associated changes in cell-mediated immunity strongly depend on thymic function ).…”

Testosterone Replacement Therapy in Reversing “Andropause”: What Is the Proof-of-Principle?

“…3 Immunosenescence, the term commonly used to describe the age-acquired dysfunctional immunity, contributes to a less-than-optimal immune response to many antigenic stimuli (i.e., from pathogens, vaccines, and diseases) compared to their younger counterparts. 3,94 Although an individual's age is a major contributor, there is no single cause of immunosenescence. 3 Thus, a compilation of immunological events are believed to result in this dysfunctional immunity, including thymic involution and the reduction in thymic output 95 ; the lifelong reshaping of the immune repertoire by persistent antigenic challenge 96 ; changes in antigen-presenting cells, including the function of their Toll-like receptor ligands 97 ; the reduced production of new B lymphocytes 98 ; and the impact of co-morbidities, 6 the nutritional status of the individual, 99 the increase frequency of chronic low-grade inflammation, 100 and the age-related dysregulation of hormonal pathways.…”