A chimeric mRNA vaccine of S-RBD with HA conferring broad protection against influenza and COVID-19 variants.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

SARS-CoV-2*/immunology ; COVID-19*/prevention & control ; COVID-19*/immunology ; mRNA Vaccines*/immunology ; Spike Glycoprotein, Coronavirus*/immunology ; Spike Glycoprotein, Coronavirus*/genetics ; Hemagglutinin Glycoproteins, Influenza Virus*/immunology ; Hemagglutinin Glycoproteins, Influenza Virus*/genetics ; COVID-19 Vaccines*/immunology; Animals ; Mice ; Humans ; Influenza Vaccines/immunology ; Antibodies, Viral/immunology ; Mice, Inbred BALB C ; Female ; Influenza A Virus, H1N1 Subtype/immunology ; Orthomyxoviridae Infections/prevention & control ; Orthomyxoviridae Infections/immunology ; Vaccines, Synthetic/immunology ; Influenza, Human/prevention & control ; Influenza, Human/immunology ; Antibodies, Neutralizing/immunology

Influenza and coronavirus disease 2019 (COVID-19) represent two respiratory diseases that have significantly impacted global health, resulting in substantial disease burden and mortality. An optimal solution would be a combined vaccine capable of addressing both diseases, thereby obviating the need for multiple vaccinations. Previously, we conceived a chimeric protein subunit vaccine targeting both influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilizing the receptor binding domain of spike protein (S-RBD) and the stalk region of hemagglutinin protein (HA-stalk) components. By integrating the S-RBD from the SARS-CoV-2 Delta variant with the headless hemagglutinin (HA) from H1N1 influenza virus, we constructed stable trimeric structures that remain accessible to neutralizing antibodies. This vaccine has demonstrated its potential by conferring protection against a spectrum of strains in mouse models. In this study, we designed an mRNA vaccine candidate encoding the chimeric antigen. The resultant humoral and cellular immune responses were meticulously evaluated in mouse models. Furthermore, the protective efficacy of the vaccine was rigorously examined through challenges with either homologous or heterologous influenza viruses or SARS-CoV-2 strains. Our findings reveal that the mRNA vaccine exhibited robust immunogenicity, engendering high and sustained levels of neutralizing antibodies accompanied by robust and persistent cellular immunity. Notably, this vaccine effectively afforded complete protection to mice against H1N1 or heterosubtypic H5N8 subtypes, as well as the SARS-CoV-2 Delta and Omicron BA.2 variants. Additionally, our mRNA vaccine design can be easily adapted from Delta RBD to Omicron RBD antigens, providing protection against emerging variants. The development of two-in-one vaccine targeting both influenza and COVID-19, incorporating the mRNA platform, may provide a versatile approach to combating future pandemics.
(Copyright: © 2024 Hao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Y.L.L., T.H., Y.B., B.Z., H.S. and G.F.G. are listed in the patent as the inventors of the influenza-COVID-19 chimeric protective vaccine. All other authors declare no competing interests.

Sci Bull (Beijing). 2023 Dec 15;68(23):3003-3012. (PMID: 37919162)
Int Immunol. 2021 Sep 25;33(10):529-540. (PMID: 34491327)
Nature. 2020 Aug;584(7819):120-124. (PMID: 32454512)
Science. 2012 Sep 14;337(6100):1343-8. (PMID: 22878502)
Proc Natl Acad Sci U S A. 2022 Sep 27;119(39):e2204624119. (PMID: 36074824)
Cell Rep. 2021 Feb 9;34(6):108728. (PMID: 33516277)
EBioMedicine. 2022 Nov;85:104297. (PMID: 36206623)
Heliyon. 2023 Mar;9(3):e13952. (PMID: 36855648)
J Clin Invest. 2019 Feb 1;129(2):850-862. (PMID: 30521496)
Hlife. 2023 Nov;1(1):26-34. (PMID: 38994526)
Vaccine. 2022 Jul 30;40(32):4412-4423. (PMID: 35680500)
Lancet Microbe. 2022 Nov;3(11):e824-e834. (PMID: 36115379)
Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2206333119. (PMID: 36322769)
Eur J Med Chem. 2021 Oct 5;221:113485. (PMID: 33965861)
Mol Ther. 2022 May 4;30(5):2024-2047. (PMID: 34999208)
Sci Rep. 2016 Mar 07;6:22666. (PMID: 26947245)
Anal Chem. 2021 May 4;93(17):6839-6847. (PMID: 33871970)
Science. 2009 Apr 10;324(5924):246-51. (PMID: 19251591)
Cold Spring Harb Perspect Med. 2021 Jun 1;11(6):. (PMID: 31988202)
Cell. 2020 Nov 12;183(4):996-1012.e19. (PMID: 33010815)
MMWR Morb Mortal Wkly Rep. 2018 Feb 16;67(6):180-185. (PMID: 29447141)
JAMA. 2023 Dec 5;330(21):2044. (PMID: 37966868)
J Infect. 2018 Sep;77(3):249-257. (PMID: 29898409)
Cell. 2020 Aug 6;182(3):744-753.e4. (PMID: 32553273)
Nat Commun. 2023 May 23;14(1):2962. (PMID: 37221158)
mLife. 2023 Sep 24;2(3):308-316. (PMID: 38817814)
Sci Adv. 2023 Jun 23;9(25):eabo4100. (PMID: 37352360)
Nature. 2020 May;581(7809):465-469. (PMID: 32235945)
J Virol. 2015 Jan;89(1):2-13. (PMID: 25320305)
Nat Rev Immunol. 2021 Feb;21(2):73-82. (PMID: 33340022)
EClinicalMedicine. 2021 Feb 03;32:100746. (PMID: 33644722)
Cell. 2020 Aug 6;182(3):722-733.e11. (PMID: 32645327)
Biosaf Health. 2023 Apr;5(2):89-100. (PMID: 37123450)
Curr Opin Drug Discov Devel. 2007 Sep;10(5):523-32. (PMID: 17786850)
Int J Infect Dis. 2023 Nov;136:29-36. (PMID: 37648094)
Emerg Microbes Infect. 2023 Dec;12(2):2231573. (PMID: 37394992)
Sci Immunol. 2021 Oct 15;6(64):eabl4509. (PMID: 34623900)
Cell. 2022 May 12;185(10):1728-1744.e16. (PMID: 35460644)
Nat Biotechnol. 2010 Feb;28(2):172-6. (PMID: 20081866)
Nat Med. 2015 Sep;21(9):1065-70. (PMID: 26301691)
Nat Rev Clin Oncol. 2023 Nov;20(11):739-754. (PMID: 37587254)
Vaccine. 2024 Feb 15;42(5):1184-1192. (PMID: 38296701)
Nat Rev Drug Discov. 2021 Nov;20(11):817-838. (PMID: 34433919)
Cell. 2022 Jun 23;185(13):2265-2278.e14. (PMID: 35568034)
Nature. 2020 Oct;586(7830):516-527. (PMID: 32967006)
Viruses. 2024 Jan 22;16(1):. (PMID: 38275973)
Emerg Microbes Infect. 2020 Dec;9(1):680-686. (PMID: 32207377)
Natl Sci Rev. 2021 Nov 03;8(10):nwab193. (PMID: 34858619)
NPJ Vaccines. 2022 Jun 29;7(1):68. (PMID: 35768475)
Science. 2015 Sep 18;349(6254):1301-6. (PMID: 26303961)
Cell Res. 2022 Nov;32(11):1022-1025. (PMID: 36104506)
Science. 2020 Aug 14;369(6505):812-817. (PMID: 32434946)
Annu Rev Biochem. 2000;69:531-69. (PMID: 10966468)
Clin Infect Dis. 2019 Mar 19;68(7):1100-1109. (PMID: 30124826)
Lancet Microbe. 2021 Oct;2(10):e494. (PMID: 34458880)
Nat Commun. 2023 Apr 12;14(1):2081. (PMID: 37045873)
Health Sci Rep. 2023 Jan 04;6(1):e1041. (PMID: 36620510)
Nat Med. 2022 Mar;28(3):472-476. (PMID: 35042228)
Cell. 2022 Feb 17;185(4):603-613.e15. (PMID: 35026152)
J Infect. 2021 Jun 27;:. (PMID: 34192524)
Cell. 2020 Sep 3;182(5):1271-1283.e16. (PMID: 32795413)

0 (mRNA Vaccines)
0 (Spike Glycoprotein, Coronavirus)
0 (Hemagglutinin Glycoproteins, Influenza Virus)
0 (COVID-19 Vaccines)
0 (Influenza Vaccines)
0 (Antibodies, Viral)
0 (Vaccines, Synthetic)
0 (Antibodies, Neutralizing)
0 (spike protein, SARS-CoV-2)

SARS-CoV-2 variants

Date Created: 20240920 Date Completed: 20240920 Latest Revision: 20240927

20250114

PMC11414905

10.1371/journal.ppat.1012508

39303003