Review
Influenza vaccine responses in older adults

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Abstract

The most profound consequences of immune senescence with respect to public health are the increased susceptibility to influenza and loss of efficacy of the current split-virus influenza vaccines in older adults, which are otherwise very effective in younger populations. Influenza infection is associated with high rates of complicated illness including pneumonia, heart attacks and strokes in the 65+ population. Changes in both innate and adaptive immune function not only converge in the reduced response to vaccination and protection against influenza, but present significant challenges to new vaccine development. In older adults, the goal of vaccination is more realistically targeted to providing clinical protection against disease rather sterilizing immunity. Correlates of clinical protection may not be measured using standard techniques such as antibody titres to predict vaccine efficacy. Further, antibody responses to vaccination as a correlate of protection may fail to detect important changes in cellular immunity and enhanced vaccine-mediated protection against influenza illness in older people. This article will discuss the impact of influenza in older adults, immunologic targets for improved efficacy of the vaccines, and alternative correlates of clinical protection against influenza that are needed for more effective translation of novel vaccination strategies to improved protection against influenza in older adults.

Research highlights

▶ Immune senescence leads to increased susceptibility to influenza and loss of vaccine efficacy. ▶ Age-related changes in innate and adaptive immune function challenge new vaccine development. ▶ Antibody titers as a sole measure of influenza vaccine efficacy may fail to detect enhanced clinical protection. ▶ Novel immunologic targets and correlates of protection are needed to develop effective vaccines.

Section snippets

Influenza—a significant cause of morbidity in older adults

Aging is associated with a decline in humoral, innate, and adaptive cell-mediated immunity and a dramatic increase in late-life morbidity and mortality from influenza. The full impact of influenza is increasingly recognized as an illness that goes well beyond pneumonia and influenza statistics. Peak months of mortality due to respiratory illness, ischemic heart disease, cerebrovascular events and diabetes in adults 70 years and older coincide with annual influenza epidemics, suggesting that

Link to immune senescence

A decline in immune function is a hallmark of aging and affects the ability to resist influenza infection and respond to vaccination. It is recognized that multiple components of immune function, particularly cell-mediated immunity, are affected during the aging process. As a consequence, there has been a paradigm shift in understanding the limitations of antibody titers as a sole measure of influenza vaccine efficacy in older people (Bernstein et al., 1999, Gardner et al., 2001, Murasko et

Cross-reactivity of the T-cell response

In contrast to the strain-specific antibody response of B-cells, viral epitopes that stimulate T helper cells (Th) and cytotoxic T lymphocytes (CTL) responses are more conserved across different strains of influenza and appear not to degrade with antigenic drift (Effros et al., 1977, Butchko et al., 1978, Russell and Liew, 1979). Virus is taken up and processed by antigen-presenting cells (APC) such as macrophages and dendritic cells, and the resulting peptides are presented with the major

High-dose vs. adjuvanted influenza vaccines

Two main strategies are being used to improve the response to influenza vaccination in older adults and include changing the content of the vaccine and evaluating alternate routes of administration to the current practice of intramuscular injection. Increasing the amount of influenza viral antigen (standardized according to HA content), adding an adjuvant to seasonal influenza vaccine, or using live-attenuated influenza strains are some of the strategies being pursued. In the case of influenza

Summary

Rising hospitalization and death rates due to influenza over the last two decades in spite of widespread influenza vaccination programs, call for more effective influenza vaccines in the older population. A greater understanding of how age-related changes and their interaction with common chronic diseases in older persons is to needed to develop new influenza vaccines with enhanced protection in this population. There have been major advances in vaccine technology but the phases of clinical

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