Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies

Abstract

Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.

Fig. 1. Age-associated alterations in the lymph nodes, DCs, B cells, and T cells.

GC germinal center, LN lymph node, DC dendritic cell, MHC major histocompatibility complex, TCR T cell receptor, TLR toll-like receptor, PD-1 programmed death receptor-1. (Created with Adobe illustrator and BioRender.com.).

Fig. 2. The main hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis.

Copyright 2023, Cell Press.

Fig. 3. The characteristics of changes in immunosenescence at the systematic, cellular, and molecular levels in elderly individuals.

The generation and maintenance of protective immunity induced by vaccination are weakened. The cGAS-STING, NLRP3 and NF-κB signaling pathways were upregulated, leading to chronic inflammation. Meanwhile, the expression of MHC, TLRs, and costimulatory molecules on APCs is reduced, leading to reduced migration to the lymph node, internalization, and antigen presentation of APCs. T cells have low expression of TCRs and costimulatory molecules, but high expression of PD-1, which leads to reduced T cell stimulation. At the molecular level, there are mainly compromised autophagy and telomere attrition. STING stimulator of interferon genes, cGAS cyclic GMP-AMP synthase, NLRP3 NOD-, LRR- and pyrin domain-containing protein 3, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, SASP senescence-associated secretory phenotype, APC antigen-presenting cell, MHC major histocompatibility complex, TCR T cell receptor, TLR toll-like receptor, PD-1 programmed death receptor-1, ATG5 autophagy-related 5, ATG7 autophagy-related 7. (Created with Adobe illustrator).

Fig. 4. Vaccine design strategies for elderly individuals include increasing the dose of antigen, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence.

AS adjuvant system, MPL monophosphoryl lipid, TLR toll-like receptor, MAPK mitogen-activated protein kinase, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells; COX cyclooxygenase; mTOR mammalian target of rapamycin; APC antigen-presenting cell; MHC major histocompatibility complex; TCR T cell receptor; PD-1 programmed death receptor-1. (Created with Adobe illustrator).