# Advanced immunology in aging population: unveiling the complexities of vaccine responsiveness **Authors:** Yan Han, Yanhao Huang, Yuanyu Zhou, Wanke He, Gaomei Luo, Liu Yang, Yanbin Chen, Yiqi Zhu, Wei Jiang, Chanchan Xiao, Jianhui Yan PMC · DOI: 10.3389/fragi.2025.1682763 · 2025-11-12 ## TL;DR This review explores how aging affects immune responses to vaccines and suggests ways to improve vaccine effectiveness in older adults. ## Contribution The paper provides a comprehensive synthesis of immunological changes in aging and novel vaccine strategies for older adults. ## Key findings - Age-related immune changes (immunosenescence) significantly impact vaccine effectiveness in older adults. - Biomarkers and advanced assays can help predict vaccine responsiveness in aging populations. - Novel vaccine formulations are being developed to enhance immune responses in older adults. ## Abstract With the accelerating global population aging, vaccine responsiveness in older adults has emerged as an increasingly critical issue. This review systematically explores age-related changes in immune system function and their impacts on vaccine efficacy. Firstly, we outline the characteristics of immunosenescence and its regulatory effects on vaccine effectiveness from three perspectives: cellular, molecular, and signaling pathway levels. Secondly, we summarize methods for predicting vaccine immune responsiveness (such as biomarkers and advanced immunological assays) and current mainstream strategies for enhancing vaccine immune responsiveness, while enumerating several prominent novel vaccine formulations targeting the older adult population. Finally, we discuss existing controversies and future research directions regarding the study of vaccine responsiveness in older adults, and comprehensively evaluate the current research status of vaccine responsiveness in this demographic. By synthesizing extensive evidence, this review aims to provide new insights into addressing the challenges of vaccinating the older adult population and lay a theoretical foundation for developing more effective immunization strategies tailored to this vulnerable group. ## Full-text entities - **Genes:** PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, Rps6kb1 (ribosomal protein S6 kinase B1) [NCBI Gene 72508] {aka 2610318I15Rik, P70S6K1, S6K, S6K-beta-1, S6K1, p70 S6K-alpha}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, PLA2G7 (phospholipase A2 group VII) [NCBI Gene 7941] {aka LDL-PLA2, LP-PLA2, PAFAD, PAFAH}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, Il11 (interleukin 11) [NCBI Gene 16156] {aka IL-11}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, S6k (Ribosomal protein S6 kinase) [NCBI Gene 38654] {aka 10539, 7-10, 7084, CG10539, DS6K, Dmel\CG10539}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, Cdkn2a (cyclin dependent kinase inhibitor 2A) [NCBI Gene 12578] {aka ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1}, NR0B2 (nuclear receptor subfamily 0 group B member 2) [NCBI Gene 8431] {aka SHP, SHP1}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, LCK (LCK proto-oncogene, Src family tyrosine kinase) [NCBI Gene 3932] {aka IMD22, LSK, YT16, p56lck, pp58lck}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, imd (immune deficiency) [NCBI Gene 44339] {aka BG5, CG5576, Dmel\CG5576, anon-WO0172774.166, dsIMD, shadok}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, PGRP-LC (Peptidoglycan recognition protein LC) [NCBI Gene 39063] {aka (PGRP)-LC, CG4432, Dm PGRP-LC, Dmel\CG4432, PGRP-LCa, PGRP-LCd}, Mgtor (Megator) [NCBI Gene 36264] {aka Bx34, CG8274, Dmel\CG8274, MTOR, Mtor, TPR}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, Ccr7 (C-C motif chemokine receptor 7) [NCBI Gene 12775] {aka CC-CKR-7, CCR-7, CD197, Cdw197, Cmkbr7, EBI1}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, Rps6ka2 (ribosomal protein S6 kinase A2) [NCBI Gene 20112] {aka 90kDa, D17Wsu134e, Rps6ka-rs1, Rsk3, p90rsk, pp90rsk}, Syx13 (Syntaxin 13) [NCBI Gene 39485] {aka CG11278, Dm Syx13, DmSyx13, Dmel\CG11278, SYN13, Syx}, mTor (mechanistic Target of rapamycin) [NCBI Gene 47396] {aka 5092, CG5092, CT16317, CT24745, CT24817, DmTOR}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1} - **Diseases:** hepatitis B (MESH:D006509), age-related sterile inflammation (MESH:D007249), influenza (MESH:D007251), pain (MESH:D010146), mitochondrial dysfunction (MESH:D028361), lupus (MESH:D008180), frailty (MESH:D000073496), CMV (MESH:D003586), infection (MESH:D007239), immune dysfunction (MESH:D007154), COVID-19 (MESH:D000086382), toxicity (MESH:D064420), IPD (MESH:D011008), deaths (MESH:D003643), viral infections (MESH:D014777), herpes zoster (MESH:D006562), cognitive decline (MESH:D003072), pertussis (MESH:D014917), sepsis (MESH:D018805), dementia (MESH:D003704), tuberculosis (MESH:D014376) - **Chemicals:** estradiol (MESH:D004958), quercetin (MESH:D011794), ketone (MESH:D007659), rapamycin (MESH:D020123), BEZ235 (MESH:C531198), canagliflozin (MESH:D000068896), water (MESH:D014867), QS-21 (MESH:C078785), dasatinib (MESH:D000069439), Oil (MESH:D009821), AS03 (MESH:C550253), AS01 (-), Losmapimod (MESH:C543534), fisetin (MESH:C017875), RAD001 (MESH:D000068338), PLGA (MESH:D000077182), NAD+ (MESH:D009243), imiquimod (MESH:D000077271), saponin (MESH:D012503), MF59 (MESH:C089950) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Mycobacterium tuberculosis (species) [taxon 1773], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Respiratory syncytial virus (no rank) [taxon 12814], Drosophila melanogaster (fruit fly, species) [taxon 7227] - **Mutations:** S6 - **Cell lines:** pMPhis3 — Mus musculus (Mouse), Hybridoma (CVCL_C6V6) ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12647025/full.md --- Source: https://tomesphere.com/paper/PMC12647025