Advanced Subunit Vaccine Delivery Technologies: From Vaccine Cascade Obstacles to Design Strategies

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2023 Sep 1

PMID 37655334

Authors

Yingying Hou

Min Chen

Yuan Bian

Xi Zheng

Rongsheng Tong

Xun Sun

Affiliations

Soon will be listed here.

Abstract

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

Citing Articles

Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines.

Xiao W, Jiang W, Chen Z, Huang Y, Mao J, Zheng W Signal Transduct Target Ther. 2025; 10(1):74.

PMID: 40038239 PMC: 11880366. DOI: 10.1038/s41392-024-02107-5.

Respiratory delivered vaccines: Current status and perspectives in rational formulation design.

Wu L, Xu W, Jiang H, Yang M, Cun D Acta Pharm Sin B. 2025; 14(12):5132-5160.

PMID: 39807330 PMC: 11725141. DOI: 10.1016/j.apsb.2024.08.026.

Unveiling the role of adhesin proteins in controlling infections: a systematic review.

Pereira I, Hartwig D Infect Immun. 2025; 93(2):e0034824.

PMID: 39772848 PMC: 11834437. DOI: 10.1128/iai.00348-24.

Advantages of Broad-Spectrum Influenza mRNA Vaccines and Their Impact on Pulmonary Influenza.

Cheng Z, Ma J, Zhao C Vaccines (Basel). 2025; 12(12.

PMID: 39772044 PMC: 11680418. DOI: 10.3390/vaccines12121382.

Vaccine Strategies Against RNA Viruses: Current Advances and Future Directions.

Hsiung K, Chiang H, Reinig S, Shih S Vaccines (Basel). 2025; 12(12.

PMID: 39772007 PMC: 11679499. DOI: 10.3390/vaccines12121345.

References

Ueno H, Klechevsky E, Schmitt N, Ni L, Flamar A, Zurawski S . Targeting human dendritic cell subsets for improved vaccines. Semin Immunol. 2011; 23(1):21-7. PMC: 3071344. DOI: 10.1016/j.smim.2011.01.004. View

Kapadia C, Tian S, Perry J, Sailer D, Luft J, DeSimone J . Extending antigen release from particulate vaccines results in enhanced antitumor immune response. J Control Release. 2017; 269:393-404. DOI: 10.1016/j.jconrel.2017.11.020. View

Ting C, Huang H, Huang T, Wu C, Chen J . The mechanisms by which pardaxin, a natural cationic antimicrobial peptide, targets the endoplasmic reticulum and induces c-FOS. Biomaterials. 2014; 35(11):3627-40. DOI: 10.1016/j.biomaterials.2014.01.032. View

Yang X, Lian K, Meng T, Liu X, Miao J, Tan Y . Immune Adjuvant Targeting Micelles Allow Efficient Dendritic Cell Migration to Lymph Nodes for Enhanced Cellular Immunity. ACS Appl Mater Interfaces. 2018; 10(39):33532-33544. DOI: 10.1021/acsami.8b10081. View

Wiig H, Swartz M . Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. Physiol Rev. 2012; 92(3):1005-60. DOI: 10.1152/physrev.00037.2011. View

Goyal S, Castrillon-Betancur J, Klaile E, Slevogt H . The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors. Front Immunol. 2018; 9:1261. PMC: 5994417. DOI: 10.3389/fimmu.2018.01261. View

Eckl-Dorna J, Batista F . BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation. Blood. 2009; 113(17):3969-77. DOI: 10.1182/blood-2008-10-185421. View

Gao W, Fang R, Thamphiwatana S, Luk B, Li J, Angsantikul P . Modulating antibacterial immunity via bacterial membrane-coated nanoparticles. Nano Lett. 2015; 15(2):1403-9. PMC: 4399974. DOI: 10.1021/nl504798g. View

Viana I, Roussel S, Defrene J, Lima E, Barabe F, Bertrand N . Innate and adaptive immune responses toward nanomedicines. Acta Pharm Sin B. 2021; 11(4):852-870. PMC: 7955583. DOI: 10.1016/j.apsb.2021.02.022. View

10.

Reddy K, Fitzmaurice K, Scott J, Harling G, Lessells R, Panella C . Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa. Nat Commun. 2021; 12(1):6238. PMC: 8556310. DOI: 10.1038/s41467-021-26557-5. View

11.

Zeng Q, Jiang H, Wang T, Zhang Z, Gong T, Sun X . Cationic micelle delivery of Trp2 peptide for efficient lymphatic draining and enhanced cytotoxic T-lymphocyte responses. J Control Release. 2014; 200:1-12. DOI: 10.1016/j.jconrel.2014.12.024. View

12.

Blanchard L, Girard J . High endothelial venules (HEVs) in immunity, inflammation and cancer. Angiogenesis. 2021; 24(4):719-753. PMC: 8487881. DOI: 10.1007/s10456-021-09792-8. View

13.

Zhang Y, Li M, Du G, Chen X, Sun X . Advancedoral vaccine delivery strategies for improving the immunity. Adv Drug Deliv Rev. 2021; 177:113928. DOI: 10.1016/j.addr.2021.113928. View

14.

Delamarre L, Pack M, Chang H, Mellman I, Trombetta E . Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science. 2005; 307(5715):1630-4. DOI: 10.1126/science.1108003. View

15.

Robbins P, Morelli A . Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014; 14(3):195-208. PMC: 4350779. DOI: 10.1038/nri3622. View

16.

Wang J, Roden R . Virus-like particles for the prevention of human papillomavirus-associated malignancies. Expert Rev Vaccines. 2013; 12(2):129-41. PMC: 3835148. DOI: 10.1586/erv.12.151. View

17.

Xie X, Hu Y, Ye T, Chen Y, Zhou L, Li F . Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen. Nat Biomed Eng. 2020; 5(5):414-428. DOI: 10.1038/s41551-020-00624-6. View

18.

Klenerman P, Hill A . T cells and viral persistence: lessons from diverse infections. Nat Immunol. 2005; 6(9):873-9. DOI: 10.1038/ni1241. View

19.

Sautes-Fridman C, Petitprez F, Calderaro J, Fridman W . Tertiary lymphoid structures in the era of cancer immunotherapy. Nat Rev Cancer. 2019; 19(6):307-325. DOI: 10.1038/s41568-019-0144-6. View

20.

Wang Y, Wang J, Zhu D, Wang Y, Qing G, Zhang Y . Effect of physicochemical properties on fate of nanoparticle-based cancer immunotherapies. Acta Pharm Sin B. 2021; 11(4):886-902. PMC: 8105773. DOI: 10.1016/j.apsb.2021.03.007. View