Immunosenescence and novel vaccination strategies for the elderly - PubMed (original) (raw)

Immunosenescence and novel vaccination strategies for the elderly

Michael G Dorrington et al. Front Immunol. 2013.

Abstract

Vaccination remains the most effective prophylactic intervention for infectious disease in the healthcare professional's toolkit. However, the efficacy and effectiveness of vaccines decrease with age. This becomes most apparent after an individual reaches 65-70 years old, and results from complex changes in the immune system that occur during aging. As such, new vaccine formulations and strategies that can accommodate age-related changes in immunity are required to protect this expanding population. Here, we summarize the consequences of immunosenescence on vaccination and how novel vaccination strategies can be designed to accommodate the aging immune system. We conclude that current vaccination protocols are not sufficient to protect our aging population and, in some cases, are an inefficient use of healthcare resources. However, researchers and clinicians are developing novel vaccination strategies that include modifying who and when we vaccinate and capitalize on existing vaccines, in addition to formulating new vaccines specifically tailored to the elderly in order to remedy this deficiency.

Keywords: adjuvants; elderly; human; immunosenescence; influenza; pneumonia; vaccination; vaccination strategies.

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Figures

Figure 1

Figure 1

Age-associated changes in immune cell frequency and function. A mixture of mouse and human experiments show differences in both the frequency and function of cells in the innate and adaptive immune compartments. HSCs in the elderly are skewed toward differentiation into myeloid progenitors at the expense of lymphoid progenitors. Elderly individuals have fewer circulating monocytes and DCs, fewer tissue-associated DCs, normal tissue macrophages, and increased splenic DCs. Naïve T and B cells populations are diminished, though mature-like T and B cells are expanded. As a result, overall antibody production and specificity is diminished in the elderly. Despite increased numbers of splenic DCs, antigen presentation is lacking at these sites in the elderly. Pro-inflammatory cytokine levels are increased in the elderly, as seen in IL-6 and TNF levels in serum samples.

Figure 2

Figure 2

Novel vaccine interventions in the elderly. Multiple novel vaccination strategies are being tested to boost the vaccine response in the elderly. High-dose vaccines increase antigen presentation as well ornamentation of follicular DCs with antigen complexes, increasing B cell activation over time. Various adjuvants (MF59, AS03, and Matrix-M™) create an “immunocompetent” environment at the injection site, increasing trafficking of DCs and monocytes to and from the site, increasing antigen uptake and presentation to T cells. TLR agonists are used to increase innate immune cell activation and, therefore, antigen presentation. Finally, viral vector vaccines increase CD8+ T cell responses by promoting antigen presentation on MHCI.

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