Durability of DNA-LNP and mRNA-LNP vaccine-induced immunity against sars-cov-2 xbb.1.5

durability-of-dna-lnp-and-mrna-lnp-vaccine-induced-immunity-against-sars-cov-2-xbb1.5
Durability of DNA-LNP and mRNA-LNP vaccine-induced immunity against sars-cov-2 xbb.1.5

Data availability

All data supporting the conclusions of this study are present in the main text and supplementary materials. Additional information is available from the corresponding authors upon request.

References

  1. Lasrado, N. et al. Waning immunity and IgG4 responses following bivalent mRNA boosting. Sci. Adv. 10, 9945 (2024).

    Google Scholar 

  2. Föhse, K. et al. The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses. Clin. Immunol. 255, 109762 (2023).

    Google Scholar 

  3. Ishii, T. et al. Waning cellular immune responses and predictive factors in maintaining cellular immunity against SARS-CoV-2 six months after BNT162b2 mRNA vaccination. Sci. Rep. 13, 1–12 (2023).

    Google Scholar 

  4. Haq, M. A. et al. Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh. Sci. Rep. 14, 1–11 (2024).

    Google Scholar 

  5. Tong, X. et al. Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination. Nat. Commun. 14, 1–15 (2023). 2023 14:1.

    Google Scholar 

  6. Moore, M., Anderson, L., Schiffer, J. T., Matrajt, L. & Dimitrov, D. Durability of COVID-19 vaccine and infection induced immunity: A systematic review and meta-regression analysis. Vaccine 54, 126966 (2025).

    Google Scholar 

  7. Srivastava, K. et al. SARS-CoV-2-infection- and vaccine-induced antibody responses are long lasting with an initial waning phase followed by a stabilization phase. Immunity 57, 587–599.e4 (2024).

    Google Scholar 

  8. Widge, A. T. et al. Durability of responses after SARS-CoV-2 mRNA-1273 vaccination. N. Engl. J. Med. 384, 80–82 (2021).

    Google Scholar 

  9. Doria-Rose, N. et al. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19. N. Engl. J. Med. 384, 2259–2261 (2021).

    Google Scholar 

  10. Pegu, A. et al. Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants. Science (1979) 373, 1372–1377 (2021).

    Google Scholar 

  11. Kim, W. et al. Germinal centre-driven maturation of B cell response to mRNA vaccination. Nature 604, 141–145 (2022).

    Google Scholar 

  12. Nguyen, D. C. et al. SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination. Nat. Med. 31, 235–244 (2025).

    Google Scholar 

  13. Florea, A. et al. Effectiveness of messenger RNA-1273 vaccine booster against coronavirus disease 2019 in immunocompetent adults. Clin. Infect. Dis. 76, 252–262 (2023).

    Google Scholar 

  14. Abu-Raddad, L. J. et al. Effect of mRNA vaccine boosters against SARS-CoV-2 omicron infection in Qatar. N. Engl. J. Med. 386, 1804–1816 (2022).

    Google Scholar 

  15. Ackerson, B. K. et al. Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages. Hum Vaccin. Immunother. 20, 2335052 (2024).

  16. Maslow, J. N. et al. DNA vaccines for epidemic preparedness: SARS-CoV-2 and beyond. Vaccine 11, 1016 (2023).

    Google Scholar 

  17. Blakney, A. K. & Bekker, L. G. DNA vaccines join the fight against COVID-19. Lancet 399, 1281–1282 (2022).

    Google Scholar 

  18. Feliciano, L. – et al. Improved DNA vaccine delivery with needle-free injection systems. Vaccines 11, 280 (2023).

    Google Scholar 

  19. Sabnis, S. et al. A novel amino lipid series for mRNA delivery: Improved endosomal escape and sustained pharmacology and safety in non-human primates. Mol. Ther. 26, 1509–1519 (2018).

    Google Scholar 

  20. Hassett, K. J. et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol. Ther. Nucleic Acids 15, 1–11 (2019).

    Google Scholar 

  21. Connors, J. et al. Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals. Commun. Biol. 6, 1–13 (2023).

    Google Scholar 

  22. Alameh, M. G. et al. Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 54, 2877–2892.e7 (2021).

    Google Scholar 

  23. Pfeifle, A. et al. DNA lipid nanoparticle vaccine targeting outer surface protein C affords protection against homologous Borrelia burgdorferi needle challenge in mice. Front Immunol. 14, 1020134 (2023).

    Google Scholar 

  24. Guimaraes, L. C. et al. Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models. Nat. Commun. 15, 1–19 (2024). 2024 15:1.

    Google Scholar 

  25. Liao, H. C. et al. Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters. Mol. Ther. Methods Clin. Dev. 32, 101169 (2024).

    Google Scholar 

  26. Tursi, N. J. et al. Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity. Cell Rep. Med 6, 102035 (2025).

    Google Scholar 

  27. Li, M. et al. Lipid nanoparticles outperform electroporation in delivering therapeutic HPV DNA vaccines. Vaccines (Basel) 12, 666 (2024).

    Google Scholar 

  28. Zhang, W. et al. The expression kinetics and immunogenicity of lipid nanoparticles delivering plasmid DNA and mRNA in mice. Vaccines (Basel) 11, 1580 (2023).

    Google Scholar 

  29. Patel, M. N. et al. Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids. Nat. Biotechnol. 2025 1–11 https://doi.org/10.1038/s41587-025-02556-5 (2025).

  30. F. D. A. Takes Action on Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants | FDA. https://www.fda.gov/news-events/press-announcements/fda-takes-action-updated-mrna-covid-19-vaccines-better-protect-against-currently-circulating.

  31. Tamming, L. A. et al. DNA based vaccine expressing SARS-CoV-2 Spike-CD40L fusion protein confers protection against challenge in a Syrian Hamster Model. Front Immunol 12, 785349 (2022).

  32. Tamming, L. et al. Lipid nanoparticle encapsulation of a Delta spike-CD40L DNA vaccine improves effectiveness against Omicron challenge in Syrian hamsters. Mol. Ther. Methods Clin. Dev. 32, 101325 (2024).

    Google Scholar 

  33. Kaku, Y., Uriu, K., Okumura, K., Ito, J. & Sato, K. Virological characteristics of the SARS-CoV-2 KP.3.1.1 variant. Lancet Infect. Dis. 24, e609 (2024).

    Google Scholar 

  34. Nunes da Silva, W., Dias Moura Prazeres, P. H. & Goulart Guimarães, P. P. PLA-PEG as an alternative to PEGylated lipids for nanoparticle-based DNA vaccination against SARS-CoV-2. Mol. Ther. Nucleic Acids 35, 102293 (2024).

    Google Scholar 

  35. Lai, D. C., Nguyen, T. N., Trinh, G. P., Steffen, D. & Vu, H. L. X. Lipid nanoparticle-encapsulated DNA vaccine induces balanced antibody and T-cell responses in pigs with maternally derived antibodies. J. Virol. https://doi.org/10.1128/JVI.01123-25 (2025).

    Google Scholar 

  36. Lai, D. C., Nguyen, T. N., Poonsuk, K., McVey, D. S. & Vu, H. L. X. Lipid nanoparticle-encapsulated DNA vaccine encoding African swine fever virus p54 antigen elicits robust immune responses in pigs. Vet. Microbiol 305, 110508 (2025).

    Google Scholar 

  37. Mucker, E. M. et al. Lipid nanoparticle formulation increases efficiency of DNA-vectored vaccines/immunoprophylaxis in animals including transchromosomic bovines. Sci. Rep. 10, 8764 (2020).

    Google Scholar 

  38. AM, H. et al. CD40 ligand preferentially modulates immune response and enhances protection against influenza virus. J. Immunol. 193, 722–734 (2014).

    Google Scholar 

  39. Kometani, K. & Kurosaki, T. Differentiation and maintenance of long-lived plasma cells. Curr. Opin. Immunol. 33, 64–69 (2015).

    Google Scholar 

  40. Brook, B. et al. Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70. Sci. Transl. Med. 16, eadm8451 (2024).

  41. Wang, L. et al. IL-7 promotes mRNA vaccine-induced long-term immunity. Immun. J. Nanobiotechnology 22, 716 (2024).

    Google Scholar 

  42. Pardi, N. et al. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Controlled Release 217, 345–351 (2015).

    Google Scholar 

  43. Swingle, K. L. et al. Circular RNA lipid nanoparticle vaccine against SARS-CoV-2. Proc. Natl. Acad. Sci. 122, e2505718122 (2025).

    Google Scholar 

  44. Qu, L. et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell 185, 1728–1744.e16 (2022).

    Google Scholar 

  45. Wan, J. et al. Circular RNA vaccines with long-term lymph node-targeting delivery stability after lyophilization induce potent and persistent immune responses. mBio 15, e0177523 (2024).

  46. Krawczyk, P. S. et al. Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines. Nature 641, 984–992 (2025).

    Google Scholar 

  47. Robinson, M. J. et al. Long-lived plasma cells accumulate in the bone marrow at a constant rate from early in an immune response. Sci Immunol 7, eabm8389 (2022).

  48. Muecksch, F. et al. Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. Immunity 54, 1853–1868.e7 (2021).

    Google Scholar 

  49. Colwill, K. et al. A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination. Clin. Transl. Immunol. 11, e1380 (2022).

    Google Scholar 

  50. Nie, J. et al. Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay. Nat. Protoc. 15, 3699–3715 (2020).

    Google Scholar 

  51. Reed, L. J. & Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Epidemiol. 27, 493–497 (1938).

    Google Scholar 

  52. Wölfel, R. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465–469 (2020).

    Google Scholar 

  53. Zivcec, M., Safronetz, D., Haddock, E., Feldmann, H. & Ebihara, H. Validation of assays to monitor immune responses in the Syrian golden hamster (Mesocricetus auratus). J. Immunol. Methods 368, 24–35 (2011).

    Google Scholar 

  54. Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔCT method. Methods 25, 402–408 (2001).

    Google Scholar 

  55. Harris, G., Holbein, B. E., Zhou, H., Howard Xu, H. & Chen, W. Potential mechanisms of mucin-enhanced acinetobacter baumannii virulence in the mouse model of intraperitoneal infection. Infect Immun 87, e00591–19 (2019).

  56. Lien, C. E. et al. CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge. Sci. Rep. 2021 11, 1–7 (2021).

    Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the histology and staining services provided by the Louise Pelletier HCF at the University of Ottawa. We gratefully acknowledge the technical contribution of Simon Lord-Dufour, Brian Cass, and Louis Bisson at the NRC-HHT for recombinant spike production. We also would like to acknowledge the assistance provided by the Animal Care Facility staff at Health Canada and the National Research Council of Canada. We thank Dr. Lu Huixin and Dr. Roger Tam for commenting on the manuscript and Greg Beaudoin for preparing the photomicrographs. Schematic representations were created in BioRender. This work is supported by the Government of Canada (intramural funding from Health Canada).

Author information

Authors and Affiliations

  1. Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada

    Levi Tamming, Casey Lansdell, Wanyue Zhang, Grant Frahm, Annabelle Pfeifle, Sathya N. Thulasi Raman, Jianguo Wu, Caroline Gravel, Andrew Stalker, Simon Sauve, Michael J. W. Johnston & Xuguang Li

  2. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

    Levi Tamming, Wanyue Zhang, Annabelle Pfeifle, Lisheng Wang, Anh Tran & Xuguang Li

  3. Human Health Therapeutics Research Center, National Research Council of Canada, Ottawa, ON, Canada

    Diana Duque, Jegarubee Bavananthasivam, Wangxue Chen & Anh Tran

  4. Human Health Therapeutics Research Center, National Research Council of Canada, Montreal, QC, Canada

    Matthew Stuible & Yves Durocher

  5. Department of Chemistry, Carleton University, Ottawa, ON, Canada

    Michael J. W. Johnston

Authors

  1. Levi Tamming
  2. Casey Lansdell
  3. Wanyue Zhang
  4. Diana Duque
  5. Jegarubee Bavananthasivam
  6. Grant Frahm
  7. Annabelle Pfeifle
  8. Sathya N. Thulasi Raman
  9. Jianguo Wu
  10. Caroline Gravel
  11. Andrew Stalker
  12. Matthew Stuible
  13. Yves Durocher
  14. Wangxue Chen
  15. Lisheng Wang
  16. Simon Sauve
  17. Anh Tran
  18. Michael J. W. Johnston
  19. Xuguang Li

Contributions

Conceptualization, L.T., A.T., M.J.W.J., X.L.; Methodology, L.T., C.L., W.Z., G.F., M.S., A.T.; Formal Analysis and Visualization, L.T., A.S.; Investigation, L.T., C.L., W.Z., D.D., J.B., G.F., A.P., S.N.R. J.W., C.G., A.S., W.C.; Resources, C.L., S.N.R., C.G., M.S., Y.D., A.T.; Writing—Original Draft, L.T.; Writing—Review & Editing, L.T., C.L., W.Z., D.D., J.B., G.F., A.P., S.N.R. J.W., C.G., A.S., M.S., Y.D., W.C., L.W., S.S., A.T., M.J.W.J., X.L.; Supervision, Y.D., L.W., S.S., A.T., M.J.W.J., X.L.; Project Administration L.T., A.T., M.J.W.J., X.L.; Funding Acquisition, Y.D., L.W., S.S., A.T., M.J.W.J., X.L.

Corresponding authors

Correspondence to Anh Tran, Michael J. W. Johnston or Xuguang Li.

Ethics declarations

Competing interests

The authors declare no Competing Financial or Non-Financial Interests to declare.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tamming, L., Lansdell, C., Zhang, W. et al. Durability of DNA-LNP and mRNA-LNP vaccine-induced immunity against sars-cov-2 xbb.1.5. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01382-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41541-026-01382-3