Dendritic-cell-targeting Virus-like Particles As Potent MRNA Vaccine Carriers

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2024 May 7

PMID 38714892

Authors

Di Yin

Yiye Zhong

Sikai Ling

Sicong Lu

Xiaoyuan Wang

Zhuofan Jiang

Jie Wang

Yao Dai

Xiaolong Tian

Qijing Huang

Xingbo Wang

Junsong Chen

Ziying Li

Yang Li

Zhijue Xu

Hewei Jiang

Yuqing Wu

Yi Shi

Quanjun Wang

Jianjiang Xu

Wei Hong

Heng Xue

Hang Yang

Yan Zhang

Lintai Da

Ze-Guang Han

Sheng-Ce Tao

Ruijiao Dong

Tianlei Ying

Jiaxu Hong

Yujia Cai

Affiliations

Soon will be listed here.

Abstract

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

Citing Articles

Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.

Balaraman A, Babu M, Afzal M, Sanghvi G, M M R, Gupta S Regen Ther. 2025; 28:558-572.

PMID: 40034540 PMC: 11872554. DOI: 10.1016/j.reth.2025.01.019.

Developing mRNA Nanomedicines with Advanced Targeting Functions.

Wang J, Cai L, Li N, Luo Z, Ren H, Zhang B Nanomicro Lett. 2025; 17(1):155.

PMID: 39979495 PMC: 11842722. DOI: 10.1007/s40820-025-01665-9.

The RNA Landscape of In Vivo-Assembled MS2 Virus-Like Particles as mRNA Carriers Reveals RNA Contamination from Host Viruses.

Ma C, Yang M, Zhou W, Guo S, Zhang H, Gong J Nano Lett. 2025; 25(8):3038-3044.

PMID: 39932477 PMC: 11869999. DOI: 10.1021/acs.nanolett.4c04541.

Nanoparticle containing recombinant excretory/secretory-24 protein of enhanced the cellular immune responses in mice.

Hasan M, Haseeb M, Gadahi J, Ehsan M, Wang Q, Lakho S Front Vet Sci. 2024; 11:1470084.

PMID: 39600880 PMC: 11588750. DOI: 10.3389/fvets.2024.1470084.

Better, Faster, Stronger: Accelerating mRNA-Based Immunotherapies With Nanocarriers.

Carvalho H, Fidalgo T, Acurcio R, Matos A, Satchi-Fainaro R, Florindo H Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024; 16(6):e2017.

PMID: 39537215 PMC: 11655444. DOI: 10.1002/wnan.2017.

References

Roth G, Picece V, Ou B, Luo W, Pulendran B, Appel E . Designing spatial and temporal control of vaccine responses. Nat Rev Mater. 2021; 7(3):174-195. PMC: 8477997. DOI: 10.1038/s41578-021-00372-2. View

Colby D, Sarnecki M, Barouch D, Tipsuk S, Stieh D, Kroon E . Safety and immunogenicity of Ad26 and MVA vaccines in acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption. Nat Med. 2020; 26(4):498-501. DOI: 10.1038/s41591-020-0774-y. View

Nguni T, Chasara C, Ndhlovu Z . Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions. Front Immunol. 2020; 11:590780. PMC: 7655734. DOI: 10.3389/fimmu.2020.590780. View

Bernstein D, Cardin R, Smith G, Pickard G, Sollars P, Dixon D . The R2 non-neuroinvasive HSV-1 vaccine affords protection from genital HSV-2 infections in a guinea pig model. NPJ Vaccines. 2020; 5(1):104. PMC: 7648054. DOI: 10.1038/s41541-020-00254-8. View

Awasthi S, Hook L, Pardi N, Wang F, Myles A, Cancro M . Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes. Sci Immunol. 2019; 4(39). PMC: 6822172. DOI: 10.1126/sciimmunol.aaw7083. View

Wang W, Zhou X, Bian Y, Wang S, Chai Q, Guo Z . Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B. Nat Nanotechnol. 2020; 15(5):406-416. PMC: 7223715. DOI: 10.1038/s41565-020-0648-y. View

Roden R, Stern P . Opportunities and challenges for human papillomavirus vaccination in cancer. Nat Rev Cancer. 2018; 18(4):240-254. PMC: 6454884. DOI: 10.1038/nrc.2018.13. View

Sahin U, Derhovanessian E, Miller M, Kloke B, Simon P, Lower M . Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017; 547(7662):222-226. DOI: 10.1038/nature23003. View

Keskin D, Anandappa A, Sun J, Tirosh I, Mathewson N, Li S . Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2018; 565(7738):234-239. PMC: 6546179. DOI: 10.1038/s41586-018-0792-9. View

10.

Polack F, Thomas S, Kitchin N, Absalon J, Gurtman A, Lockhart S . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020; 383(27):2603-2615. PMC: 7745181. DOI: 10.1056/NEJMoa2034577. View

11.

Baden L, El Sahly H, Essink B, Kotloff K, Frey S, Novak R . Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020; 384(5):403-416. PMC: 7787219. DOI: 10.1056/NEJMoa2035389. View

12.

Widge A, Rouphael N, Jackson L, Anderson E, Roberts P, Makhene M . Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination. N Engl J Med. 2020; 384(1):80-82. PMC: 7727324. DOI: 10.1056/NEJMc2032195. View

13.

Thomas S, Moreira Jr E, Kitchin N, Absalon J, Gurtman A, Lockhart S . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. N Engl J Med. 2021; 385(19):1761-1773. PMC: 8461570. DOI: 10.1056/NEJMoa2110345. View

14.

Wang Y, Zhang Z, Luo J, Han X, Wei Y, Wei X . mRNA vaccine: a potential therapeutic strategy. Mol Cancer. 2021; 20(1):33. PMC: 7884263. DOI: 10.1186/s12943-021-01311-z. View

15.

Lindsay K, Bhosle S, Zurla C, Beyersdorf J, Rogers K, Vanover D . Visualization of early events in mRNA vaccine delivery in non-human primates via PET-CT and near-infrared imaging. Nat Biomed Eng. 2019; 3(5):371-380. DOI: 10.1038/s41551-019-0378-3. View

16.

Chen J, Ye Z, Huang C, Qiu M, Song D, Li Y . Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8 T cell response. Proc Natl Acad Sci U S A. 2022; 119(34):e2207841119. PMC: 9407666. DOI: 10.1073/pnas.2207841119. View

17.

Tenforde M, Patel M, Ginde A, Douin D, Talbot H, Casey J . Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccines for Preventing Coronavirus Disease 2019 Hospitalizations in the United States. Clin Infect Dis. 2021; 74(9):1515-1524. PMC: 8436392. DOI: 10.1093/cid/ciab687. View

18.

Eisenbarth S . Dendritic cell subsets in T cell programming: location dictates function. Nat Rev Immunol. 2018; 19(2):89-103. PMC: 7755085. DOI: 10.1038/s41577-018-0088-1. View

19.

Lanzavecchia A, Sallusto F . Regulation of T cell immunity by dendritic cells. Cell. 2001; 106(3):263-6. DOI: 10.1016/s0092-8674(01)00455-x. View

20.

Heath W, Kato Y, Steiner T, Caminschi I . Antigen presentation by dendritic cells for B cell activation. Curr Opin Immunol. 2019; 58:44-52. DOI: 10.1016/j.coi.2019.04.003. View