In a recent review published in Nature Aging, researchers explored vaccine-based therapeutics for age-related disorders.

Study: Targeting aging and age-related diseases with vaccines. Image Credit: Ground Picture/Shutterstock.com

Background

Aging is a primary risk factor for chronic illnesses, marked by reduced physiological capabilities. Cell senescence, genomic instability, stem cell fatigue, and mitochondrial failure are characteristics.

Aging also increases the risk of chronic illnesses such as Alzheimer’s disease, atherosclerosis, osteoarthritis, type 2 diabetes, chronic obstructive pulmonary disease (COPD), and cancer. Healthy habits like calorie control and regular physical exercise help prevent age-related disorders.

However, small-molecule therapies have limits, and vaccines provide a potential technique to target specific antigens to generate immune responses.

About the review

In the present review, researchers present new developments in vaccines using senescent cells to target the etiological agents of aging and related diseases.

Immunology of senolytic vaccines that target aging

Vaccines stimulate the innate immunological system, making it rapidly respond to infection. This reaction activates adaptive immune cells, causing humoral antibodies to manufacture antibodies and cell-mediated immunity to attack infected cells. Vaccinations lead to pathogen-targeted memory cell development to accelerate response to reinfections.
Vaccines targeting microbes, cell populations, or chemicals can prevent and treat disease development. Senolytic vaccines, which target senescent cells, have been demonstrated to reduce arterial plaque development.

These vaccination techniques provide new pathways for managing age-associated disorders, with advantages such as fewer injections, increased patient adherence, cost-effectiveness, and improved targeting efficiency.

Senolytic vaccinations target senescent cells by targeting chemicals on their surfaces, using peptide-based platforms to eradicate them through complement-dependent cytotoxicity (CDC) or natural killer (NK) cell-mediated and antibody-dependent cell-mediated cytotoxicity (ADCC).

Membrane proteins overexpressed in senescent cells are used as vaccine antigens or immune cell targets to stimulate the development of specific antibodies.

Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) trigger a cluster of differentiation 4-expressing helper T cells, CD8+ cytotoxic T cells, and B cells to kill cancer cells.

Cancer vaccines use cell-based, virus-based, peptide-based, and nucleic acid-based platforms to stimulate adaptive immunity.

Research on vaccine-based strategies for age-related disorders

Alzheimer’s disease (AD) vaccinations attempt to lower the brain’s amyloid-beta (Aβ) and tau protein levels by stimulating the adaptive immune system to produce antibodies. Peptides with neuroprotective properties are potentially possible therapies.

Vaccines like ACI-24, UB-311, AV-1959D, ABvac40, ACI-35, AADvac1, and GV1001 target Aβ and tau proteins in innate immune cells. ACI-24 targets Aβ1-15 liposomes, UB-311 targets Aβ protein, AV-1959D targets deoxyribonucleic acid (DNA), ABvac40 targets Aβ protein, ACI-35 targets tau protein accumulation, and AADvac1 and GV1001 demonstrate long-term safety, tolerance, and immunogenicity.

Type 2 diabetes vaccinations target molecules like dipeptidyl-peptidase 4 (DPP4) and interleukin-1 beta (IL-1β) to restore levels and prevent problems.

The vaccines use peptide sequences to produce anti-DPP4 antibodies, increase glucose tolerance, restore beta cell mass, and reduce IL-1β production. They also couple prorenin epitopes with keyhole limpet hemocyanin (KLH), improving retinal blood circulation, decreasing microglia activation, and reducing gliosis and vascular leakage in diabetic rats.

Vaccines for age-related vascular diseases such as hypertension, abdominal aortic aneurysm (AAA), and atherosclerosis target molecules that regulate blood pressure, cholesterol, and blood vessel function. PMD-2850, PMD-3117, CYT006-AngQb, AT1R, ATRQβ-001, and ADR-004 inhibit angiopoietin 1 (Ang I) and age-related accumulation in hypertensive rats.

Vaccines containing KLH and Ang II decreased macrophage aggregation in the AAA wall, suppressed tumor necrosis factor (TNF) expression, and protected against elastic fiber injury.

The nerve growth factor (NGF) protein is an osteoarthritis target. Researchers covalently linked recombinant NGF proteins to virus-like particles (VLPs) derived from a cucumber mosaic virus with tetanus toxoid epitopes.

Vaccinated mice developed measurable antibodies against NGF and showed reversed pain behavior. ADAM metallopeptidase domain 12 (ADAM12) and GLI family zinc finger 1 (GLI1) levels are associated with fibrosis. Lentiviral vectors that encode these proteins decrease fibrotic activity in mice.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) can treat fibrosis. PCSK9Qβ-003, an epitope peptide, enhanced kidney fibrosis, and increased fatty acid beta-oxidation-associated variables among Ldlr+/− murine animals. The vaccine can treat kidney fibrosis, hypercholesterolemia, and atherosclerosis.

Conclusions

Based on the review findings, senescent cells play a significant role in age-related chronic disorders and demonstrate immunogenicity, making them candidates for targeted vaccine elimination.

However, vaccinations can cause adverse effects such as injection site redness, discomfort, fever, and headaches. Continuous evaluation of vaccination safety is required to comprehend long-term adverse effects.  

Vaccines targeting key mediators in age-related disorders have seldom proven efficacy in slowing disease development. Researchers must select antigens from key disease drivers or investigate epitopes generating robust immune responses to boost vaccination effectiveness.

Combinatorial therapy incorporating vaccinations and immunomodulatory medications may be more effective.