Challenges in the Vaccination of the Elderly and Strategies for Improvement

Abstract

In recent years, the elderly has become a rapidly growing proportion of the world's population as life expectancy is extending. Immunosenescence and inflammaging contribute to the increased risk of chronic non-communicable and acute infectious diseases. Frailty is highly prevalent in the elderly and is associated with an impaired immune response, a higher propensity to infection, and a lower response to vaccines. Additionally, the presence of uncontrolled comorbid diseases in the elderly also contributes to sarcopenia and frailty. Vaccine-preventable diseases that threaten the elderly include influenza, pneumococcal infection, herpes zoster, and COVID-19, which contribute to significant disability-adjusted life years lost. Previous studies had shown that conventional vaccines only yielded suboptimal protection that wanes rapidly in a shorter time. This article reviews published papers on several vaccination strategies that were developed for the elderly to solve these problems: more immunogenic vaccine formulations using larger doses of antigen, stronger vaccine adjuvants, recombinant subunit or protein conjugated vaccines, newly developed mRNA vaccines, giving booster shots, and exploring alternative routes of administration. Included also are several publications on senolytic medications under investigation to boost the immune system and vaccine response in the elderly. With all those in regard, the currently recommended vaccines for the elderly are presented.

Keywords: comparative effectiveness analysis; elderly; frailty; immunosenescence; infection; recommended vaccine.

Figure 1

The multisystem aging process and frailty. Redrawn and adapted from Thillainadesan, J., et al. [19].

Figure 2

Interconnection between immunity, frailty, and infection. Redrawn and adapted from Vetrano, D.L., et al. [10].

Figure 3

Changes in the response to vaccines in the elderly. (1) Subclinical inflammation increases the threshold of „danger” signals to be induced by vaccines augmented with adjuvant. (2) Functionally defective antigen-presenting cells will interfere with the uptake and the presentation of antigens. (3) Involution of the thymus gland leads to the advanced loss of naïve T cells, thus compromising the success of primary vaccination. (4) Reduced B cell production and faults in isotype switching and somatic hypermutation result in weak and low-affinity antibody responses. (5) An increased number of effector T cells limits immune cell diversity and threatens the desired effects of vaccination. (6) The aging process in the stroma of the bone marrow can compromise the viability of plasma cells and shorten the duration of immunological protection. Redrawn and adapted from Weinberger, B., et al. [49].