In response to the “aging of the global population” and growing risks from various diseases, authors for npj vaccines consider the challenges and opportunities associated with vaccinating elderly individuals. To allow a greater understanding of the role of immunosenescence in vaccine efficacy, they characterise immunosenescence at cellular and molecular levels. They also summarise strategies to “improve vaccination potency in elderly individuals”. When considering the importance of, and difficulties with, adult immunisations at the Congress in Washington, some of our speakers touched on the issues explored here, and protecting aging communities is a key consideration for many in our community.
Aging: a process as old as time
“Aging is a common, inevitable, and complex process in nature.”
While the authors acknowledge that aging is a natural process, they identify a “worldwide concern” in the aging global population; by 2050 the global population over 60 is expected to increase to 2.1 billion. The medical challenges that aging presents are associated with a “decline in physiological function and progress immune system degradation”.
“The public health service and healthcare systems are facing severe challenges caused by aging.”
A modern success story
“Vaccination is one of the most important successes of modern medicine and is a powerful weapon for preventing and treating fatal infectious diseases.”
The authors state that vaccines have, over decades, saved “hundreds of millions of lives”, and a collective awareness of the importance of vaccines in “controlling disease outbreaks and protecting older people” is growing. Current recommendations for individuals over 65 years include influenza, herpes zoster, RSV, and diphtheria.
However, vaccination efficiency can be “reduced” due to immunosenescence. This is exemplified in the age-related capacity of influenza vaccines to induce immune protection: efficacy ranges from 70% to 90% in young people but decreases to 30% to 50% in people over 65 years.
“Immunosenescence is a complex process that involves organ reorganisation and numerous regulatory processes at the cellular level. The decline in the amount and function of immune cells results in impaired immune responses.”
As elderly people face increased risks of infection and are the “most challenging to protect by vaccination”, the authors identify a need for research and development of adjuvants and vaccine systems to offer “high-efficacy immune protection for elderly individuals”. Thus, they emphasise the importance of “extensive knowledge” of immunosenescence, its relation to vaccination, and its immunological mechanisms to “provide scientific insights to optimise vaccines for elderly individuals.” In the article they analyse alterations “mediated by immunosenescence at the cellular and molecular levels” and review “emerging strategies” to “boost the potency of vaccines in elderly individuals”.
How does immunosenescence affect immunity?
The authors state that “immunological and molecular signatures” of older people are different to younger people. For example, a study on immune responses to an influenza vaccine found that those who didn’t respond to the vaccine “presented with multiple states of immune inhibition”.
“In general, the number and function of naïve B and T cells in older individuals are reduced, resulting in weakened immunity to neoantigens.”
Furthermore, while aging immune cells can generate “a sufficient primary antibody response”, they often do so “at a slower rate and with a lower ability to neutralise pathogens”. CD4+ and CD8+ T cell responses are “also diminished”.
Immunosenescence is also accompanied by “the development of a chronic and systemic sterile inflammatory environment called inflammaging”. The levels of factors such as C-reactive protein and other proinflammatory cytokines are “higher” in older adults. The acute inflammatory reaction is “essential” to trigger immunity against invasive pathogens, but reduces for a period after initial inflammation to avoid “continuous tissue damage” and to “restore tissue homeostasis”.
“Chronic inflammation negatively impacts immunity because increases in the inflammatory response reduce the effectiveness of vaccines.”
Chronic inflammation is attributed to “multiple mechanisms”, and the decrease in efferocytosis and cthe clearance of apoptotic neutrophils during the regression phase of inflammation weakens an older individual’s ability to resolve inflammation.
The authors identify important advances in research on signaling pathways and molecular mechanisms to influence senescence. Molecular hallmarks of aging have been proposed, such as genomic instability, telomere attrition, epigenetic alterations, and mitochondrial dysfunction. They suggest that compromised autophagy, the loss of proteostasis, and telomere attrition could affect the immune responses induced by vaccines.
What can vaccine developers do?
“Although the vaccine-induced immunity of elderly individuals is significantly reduced, some strategies are still available to enhance protective immunity. Understanding what strategies already exist in this field is imperative for the development of other high-efficacy vaccines for elderly individuals.”
Strategies include:
- High-dose vaccines – an increased antigen dose could increase immunogenicity and induce long-lasting T cell and B cell responses.
- Multivalent vaccines – an “excellent choice”, having proven effective in practice, but studies should focus on evaluating if they can induce more neutralising antibodies and cross-neutralisation against other viral variants.
- Adjuvanted vaccines – adding appropriate adjuvants can decrease the required antigen dosage, reduce the number of vaccinations needed, and broaden immune protection; useful adjuvants should “facilitate innate and adaptive immunity and produce long-lasting protective memory” as well as “strike a balance between reduced inflammation and the low inflammatory state”.
- Inhibiting chronic inflammation – regulating baseline inflammation before vaccination could elicit immune responses.
- Inhibiting immunosenescence – this could be a “critical measure” to improve immune responses, presenting an “attractive direction for future research”.
The paper concludes that there is an “urgent” need to create strategies to improve vaccination-mediated protection for the aging population. The current approaches, the authors suggest, are primarily aimed at “optimising the vaccine delivery system” instead of tackling immunosenescence.
“Inhibiting the immunosenescence of elderly individuals can evoke strong and long-lasting immune protection, which serves as a critical measure to improve vaccine-induced immunity.”
Although this inhibition would likely require continuous intervention and would be complicated, the authors believe sustained-release vaccination/adjuvants or booster immunisations “may sustainably ameliorate immunosenescence”. Following this, the immune efficacy of elderly people against various antigens “can be improved”. Alongside methods to improve vaccine efficiency, there can be efforts to alter the route of administration. For example, mucosal routes may be “promising”.
What do you think of the issues and approaches explored in the article, and how does immunosenescence inform your work? For more on the latest reviews and releases don’t forget to subscribe to our weekly newsletters here!
