# Emerging novel methodologies to understand and strategically target long-lived plasma cells in vaccine design to induce durable immunity

**Authors:** Gina Cusimano, Ryan P. Staupe, Nicole L. Sullivan

PMC · DOI: 10.3389/fimmu.2025.1680375 · Frontiers in Immunology · 2026-02-06

## TL;DR

This paper reviews how long-lived plasma cells help create lasting immunity and how new methods can improve vaccine design to target these cells.

## Contribution

The paper introduces emerging technologies to better understand and target long-lived plasma cells for improved vaccine design.

## Key findings

- LLPCs are crucial for long-term immunity but their formation signals are not fully understood.
- New technologies can help study LLPC biology and improve vaccine strategies.
- Vaccine design decisions significantly impact immunological memory and LLPC generation.

## Abstract

Long-lived plasma cells (LLPCs) are a subset of antibody secreting cells (ASCs) that reside within lymphoid tissues, including the bone marrow (BM) and gut associated lymphoid tissues (GALT), and can secrete antigen-specific antibodies for up to decades or longer. Due to these traits, LLPCs serve as a crucial mediator for durable protective immunity. The signals needed to control the differentiation of LLPCs from naïve B cells, however, are not well understood. Accordingly, it remains a challenge to design vaccines that specifically drive LLPC generation and subsequent antibody durability. In this review, we discuss LLPC generation and heterogeneity following vaccination, vaccine design decisions known to impact immunological memory, and how novel emerging technologies can be used to inform on LLPC biology to enable LLPC targeting vaccine design.

## Full-text entities

- **Genes:** Ly6a (lymphocyte antigen 6 family member A) [NCBI Gene 110454] {aka Ly-6A.2, Ly-6A/E, Ly-6E.1, Sca-1, Sca1, TAP}, Cd27 (CD27 antigen) [NCBI Gene 21940] {aka S152, Tnfrsf7, Tp55}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, MYB (MYB proto-oncogene, transcription factor) [NCBI Gene 4602] {aka Cmyb, c-myb, c-myb_CDS, efg}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, AICDA (activation induced cytidine deaminase) [NCBI Gene 57379] {aka AID, ARP2, CDA2, HEL-S-284, HIGM2}, Cd38 (CD38 antigen) [NCBI Gene 12494] {aka ADPRC 1, Cd38-rs1, I-19}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, Sdc1 (syndecan 1) [NCBI Gene 20969] {aka CD138, Sstn, Synd, Synd1, syn-1}, Tlr9 (toll-like receptor 9) [NCBI Gene 81897], CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, Cd19 (CD19 antigen) [NCBI Gene 12478], Bcr (BCR activator of RhoGEF and GTPase) [NCBI Gene 110279] {aka 5133400C09Rik, mKIAA3017}, Cxcr4 (C-X-C motif chemokine receptor 4) [NCBI Gene 12767] {aka CD184, CXC-R4, CXCR-4, Cmkar4, LESTR, PB-CKR}, CCR10 (C-C motif chemokine receptor 10) [NCBI Gene 2826] {aka GPR2}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, ERVK-20 (endogenous retrovirus group K member 20) [NCBI Gene 100616444] {aka c11_B, env}, BLNK (B cell linker) [NCBI Gene 29760] {aka AGM4, BASH, BLNK-S, LY57, SLP-65, SLP65}, Icam2 (intercellular adhesion molecule 2) [NCBI Gene 15896] {aka CD102, Icam-2, Ly-60}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, S1PR1 (sphingosine-1-phosphate receptor 1) [NCBI Gene 1901] {aka CD363, CHEDG1, D1S3362, ECGF1, EDG-1, EDG1}, Tlr7 (toll-like receptor 7) [NCBI Gene 170743], Ighv1-62 (immunoglobulin heavy variable 1-62) [NCBI Gene 668542] {aka IgG, IgM, IgVH, Igh}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, SDC1 (syndecan 1) [NCBI Gene 6382] {aka CD138, SDC, SYND1, syndecan}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, Ighm (immunoglobulin heavy constant mu) [NCBI Gene 16019] {aka Igh-6, Igh-M, Igh6, Igm, TC1460681, muH}, Cd40 (CD40 antigen) [NCBI Gene 21939] {aka Bp50, GP39, HIGM1, IGM, IMD3, T-BAM}, PRDM1 (PR/SET domain 1) [NCBI Gene 639] {aka BLIMP-1, BLIMP1, PRDI-BF1}, GPI (glucose-6-phosphate isomerase) [NCBI Gene 2821] {aka AMF, CNSHA4, GNPI, NLK, PGI, PHI}, CCR9 (C-C motif chemokine receptor 9) [NCBI Gene 10803] {aka CC-CKR-9, CDw199, GPR-9-6, GPR28}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, PLAAT4 (phospholipase A and acyltransferase 4) [NCBI Gene 5920] {aka HRASLS4, HRSL4, PLA1/2-3, PLAAT-4, RARRES3, RIG1}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}
- **Diseases:** viral infections (MESH:D014777), influenza (MESH:D007251), inflammation (MESH:D007249), trauma (MESH:D014947), cancer (MESH:D009369), measles, mumps, and rubella (MESH:D009107), infection (MESH:D007239), GC (MESH:C548085), hemorrhage (MESH:D006470), hypoxic (MESH:D002534), ASC (MESH:D065309), measles (MESH:D008457), yellow fever (MESH:D015004), LLPC (MESH:D007952), Tetanus (MESH:D013746), smallpox (MESH:D012899), MBC (MESH:D015448), malaria (MESH:D008288)
- **Chemicals:** 3M-052 (MESH:C000626991), Aluminum (MESH:D000535), heparan sulfate (MESH:D006497), AS01 (-), Oil (MESH:D009821), AS03 (MESH:C550253), chromium (MESH:D002857), alpha-tocopherol (MESH:D024502), QS-21 (MESH:C078785), squalene (MESH:D013185), lipid (MESH:D008055), LPS (MESH:D008070), MF59 (MESH:C089950), water (MESH:D014867), phosphoserine (MESH:D010768), saponin (MESH:D012503), MPLA (MESH:C048436), Matrix M (MESH:C000625666), R848 (MESH:C402365), Biotin (MESH:D001710)
- **Species:** Human immunodeficiency virus (species) [taxon 12721], Homo sapiens (human, species) [taxon 9606], Human papillomavirus (species) [taxon 10566], Mus musculus (house mouse, species) [taxon 10090], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Human immunodeficiency virus 1 (no rank) [taxon 11676]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920446/full.md

## References

187 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920446/full.md

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Source: https://tomesphere.com/paper/PMC12920446