Universal broad-spectrum mucosal vaccine design for human coronaviruses inspired by artificial antibodies

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Universal broad-spectrum mucosal vaccine design for human coronaviruses inspired by artificial antibodies

References

  1. Su, S. et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 24, 490–502 (2016).

    Google Scholar 

  2. Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020).

    Google Scholar 

  3. Liu, J. et al. Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations. Lancet Infect. Dis. 25, e6–e7 (2025).

    Google Scholar 

  4. Callaway, E. Beyond Omicron: what’s next for COVID’s viral evolution. Nature 600, 204–207 (2021).

    Google Scholar 

  5. Chen, J. et al. Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor. Cell 188, 1729–1742.e1716 (2025).

    Google Scholar 

  6. Li, Q. et al. The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity. Cell 182, 1284–1294.e1289 (2020).

    Google Scholar 

  7. Wellford, S. A. et al. Mucosal plasma cells are required to protect the upper airway and brain from infection. Immunity 55, 2118–2134.e2116 (2022).

    Google Scholar 

  8. Kumari, M. et al. Multivalent mRNA vaccine elicits broad protection against SARS-CoV-2 variants of concern. Vaccines 12, 714 (2024).

    Google Scholar 

  9. Yang, J. et al. A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern. Cell Mol. Immunol. 19, 1279–1289 (2022).

    Google Scholar 

  10. Zhang, Y. et al. Mosaic RBD nanoparticles elicit protective immunity against multiple human coronaviruses in animal models. Adv. Sci. 11, e2303366 (2024).

    Google Scholar 

  11. Zhao, Y. et al. Vaccination with S(pan), an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice. Sci. Transl. Med. 15, eabo3332 (2023).

    Google Scholar 

  12. Tada, T., Peng, J. Y., Dcosta, B. M. & Landau, N. R. Single-epitope T cell-based vaccine protects against SARS-CoV-2 infection in a preclinical animal model. JCI Insight 8, e167306 (2023).

    Google Scholar 

  13. Kim, S. H. et al. Influenza virus-derived CD8 T cell epitopes: implications for the development of universal influenza vaccines. Immune Netw. 24, e19 (2024).

    Google Scholar 

  14. Liu, Z., Lu, L. & Jiang, S. Application of “B+1” heterologous boosting strategy for preventing infection of SARS-CoV-2 variants with resistance to broad-spectrum coronavirus vaccines. Emerg. Microbes Infect. 12, 2192817 (2023).

    Google Scholar 

  15. Tricou, V. et al. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2-17 years: a randomised, placebo-controlled, phase 2 trial. Lancet 395, 1434–1443 (2020).

    Google Scholar 

  16. Zhao, F., Zai, X., Zhang, Z., Xu, J. & Chen, W. Challenges and developments in universal vaccine design against SARS-CoV-2 variants. NPJ Vaccines 7, 167 (2022).

    Google Scholar 

  17. Sun, B. et al. An intranasally administered adenovirus-vectored SARS-CoV-2 vaccine induces robust mucosal secretory IgA. JCI Insight 9, e180784 (2024).

    Google Scholar 

  18. Chen, J. et al. Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters. PNAS Nexus 3, pgae183 (2024).

    Google Scholar 

  19. Baldeon Vaca, G. et al. Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection. Sci. Adv. 9, eadh1655 (2023).

    Google Scholar 

  20. Li, W. et al. An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission. Nat. Commun. 14, 7114 (2023).

    Google Scholar 

  21. Anthi, A. K. et al. An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models. Nat. Commun. 16, 3999 (2025).

    Google Scholar 

  22. Ochsner, S. P. et al. FcRn-targeted mucosal vaccination against influenza virus infection. J. Immunol. 207, 1310–1321 (2021).

    Google Scholar 

  23. Morens, D. M., Taubenberger, J. K. & Fauci, A. S. Universal coronavirus vaccines – an urgent need. N. Engl. J. Med. 386, 297–299 (2022).

    Google Scholar 

  24. Wu, Y. et al. Anti-TGF-beta/PD-L1 bispecific antibody synergizes with radiotherapy to enhance antitumor immunity and mitigate radiation-induced pulmonary fibrosis. J. Hematol. Oncol. 18, 24 (2025).

    Google Scholar 

  25. Tapryal, S. Monoclonal antibodies – a repertoire of therapeutics. Adv. Protein Chem. Struct. Biol. 144, 151–212 (2025).

    Google Scholar 

  26. Pan, X. et al. RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates. Cell Discov. 7, 82 (2021).

    Google Scholar 

  27. Wu, Y. et al. Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants. J. Virol. 97, e0127923 (2023).

    Google Scholar 

  28. Pan, X. et al. Immunoglobulin fragment F(ab’)(2) against RBD potently neutralizes SARS-CoV-2 in vitro. Antivir. Res. 182, 104868 (2020).

    Google Scholar 

  29. Xu, D. et al. In vitro characterization of five humanized OKT3 effector function variant antibodies. Cell Immunol. 200, 16–26 (2000).

    Google Scholar 

  30. Vafa, O. et al. An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations. Methods 65, 114–126 (2014).

    Google Scholar 

  31. Foss, S. et al. Enhanced FcRn-dependent transepithelial delivery of IgG by Fc-engineering and polymerization. J. Control Release 223, 42–52 (2016).

    Google Scholar 

  32. Ruan, W. et al. SARS-CoV-2 serotyping based on spike antigenicity and its implications for host immune evasion. EBioMedicine 114, 105634 (2025).

    Google Scholar 

  33. Liu, Z. et al. A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs. Cell Res. 32, 269–287 (2022).

    Google Scholar 

  34. Wu, Y. et al. A recombinant spike protein subunit vaccine confers protective immunity against SARS-CoV-2 infection and transmission in hamsters. Sci. Transl. Med. 13, eabg1143 (2021).

    Google Scholar 

  35. Ye, T. et al. Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization. Nature 624, 630–638 (2023).

    Google Scholar 

  36. Xu, K. et al. Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2. Cell 185, 2265–2278.e2214 (2022).

    Google Scholar 

  37. Nachbagauer, R. et al. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat. Med. 27, 106–114 (2021).

    Google Scholar 

  38. Zhang, J., Yi, J. & Zhou, P. Development of bispecific antibodies in China: overview and prospects. Antib. Ther. 3, 126–145 (2020).

    Google Scholar 

  39. Seo, J., Polster, J., Israelow, B., Corbett-Helaire, K. S. & Martinez, D. R. Challenges for developing broad-based mucosal vaccines for respiratory viruses. Nat. Biotechnol. 42, 1765–1767 (2024).

    Google Scholar 

  40. France, M. M. & Turner, J. R. The mucosal barrier at a glance. J. Cell Sci. 130, 307–314 (2017).

    Google Scholar 

  41. Uddback, I. et al. Prevention of respiratory virus transmission by resident memory CD8(+) T cells. Nature 626, 392–400 (2024).

    Google Scholar 

  42. Zhu, F. et al. Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir. Med. 11, 1075–1088 (2023).

    Google Scholar 

  43. Zhang, X. et al. Progress and challenges in the clinical evaluation of immune responses to respiratory mucosal vaccines. Expert Rev. Vaccines 23, 362–370 (2024).

    Google Scholar 

  44. Fischer, H. & Widdicombe, J. H. Mechanisms of acid and base secretion by the airway epithelium. J. Membr. Biol. 211, 139–150 (2006).

    Google Scholar 

  45. Baker, K. et al. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 108, 9927–9932 (2011).

    Google Scholar 

  46. Meinhardt, J. et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci. 24, 168–175 (2020).

    Google Scholar 

  47. Ueha R., et al. Oral SARS-CoV-2 inoculation causes nasal viral infection leading to olfactory bulb infection: an experimental study. Front. Cell Infect. Microbiol. 12, 924725 (2022).

  48. Koralnik, I. J. & Tyler, K. L. COVID-19: a global threat to the nervous system. Ann. Neurol. 88, 1–11 (2020).

    Google Scholar 

  49. Hale, G. Living in LALA land? Forty years of attenuating Fc effector functions. Immunol. Rev. 328, 422–437 (2024).

    Google Scholar 

  50. Zhang, Y. et al. An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters. NPJ Vaccines 10, 100 (2025).

    Google Scholar 

  51. Damdinsuren, B. et al. Single round of antigen receptor signaling programs naive B cells to receive T cell help. Immunity 32, 355–366 (2010).

    Google Scholar 

  52. Kim, M.-Y., Mason, H. S., Ma, J. K. C. & Reljic, R. Recombinant immune complexes as vaccines against infectious diseases. Trends Biotechnol. 42, 1427–1438 (2024).

    Google Scholar 

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