流感病毒血凝素表位通用疫苗设计的研究进展
Research Progress on Universal Vaccine Design of Influenza Virus Hemagglutinin Epitopes
DOI: 10.12677/acm.2024.1441060, PDF,   
作者: 郭志杰, 徐翠香*：西安医学院研究生工作部，陕西 西安；郭春艳：陕西省人民医院中心实验室，陕西 西安
关键词: 流感病毒；通用疫苗；血凝素；保守表位；中和表位；Influenza Virus； Universal Vaccine； Hemagglutinin； Conserved Epitope； Neutralizing Epitope
摘要: 尽管流感是一个可预防性疾病，但它仍然是一个持续性的公共卫生问题，据统计每年可导致数十万人死亡。由于流感病毒的高度可变性，不可避免地存在疫苗与流行毒株抗原不一致的风险，迫切需要一种具有广泛保护作用或通用的流感病毒疫苗，以预防所有季节性、人畜共患和新出现的大流行流感病毒。流感病毒表面糖蛋白血凝素具有广谱中和抗体识别的位点，被认为是通用疫苗研发的关键靶标，因此血凝素保守保护性表位及中和表位的鉴定对于设计通用流感疫苗和新的靶向治疗至关重要。在这里，本文综述了基于流感病毒血凝素保守表位及中和表位的通用疫苗设计研究进展。
Abstract: Although influenza is a preventable disease, it is still a persistent public health problem that can cause hundreds of thousands of deaths annually. Due to the high variability of influenza viruses, there is an inevitable risk of inconsistency between vaccines and the antigens of epidemic strains. There is an urgent need for a widely protective or universal influenza virus vaccine to prevent all seasonal, zoonotic and emerging pandemic influenza viruses. Hemagglutinin, a glycoprotein on the surface of influenza virus, has broad-spectrum neutralizing antibody recognition sites and is considered to be a key target for the development of universal vaccines. Therefore, the identification of conserved protective epitopes and neutralizing epitopes of hemagglutinin is essential for the design of universal influenza vaccines and new targeted therapies. Here, this paper reviews the research progress in universal vaccine design based on the conserved epitopes and neutralizing epitopes of influenza virus hemagglutinin.
文章引用：郭志杰, 郭春艳, 徐翠香. 流感病毒血凝素表位通用疫苗设计的研究进展[J]. 临床医学进展, 2024, 14(4): 562-567. https://doi.org/10.12677/acm.2024.1441060

参考文献

[1] WHO (2023) Influenza (Seasonal)
https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)
[2] Li, J., Zhang, Y., Zhang, X., et al. (2022) Influenza and Universal Vaccine Research in China. Viruses, 15, Article 116. [Google Scholar] [CrossRef] [PubMed]
[3] Nypaver, C., Dehlinger, C. and Carter, C. (2021) Influenza and Influenza Vaccine: A Review. Journal of Midwifery & Women’s Health, 66, 45-53. [Google Scholar] [CrossRef] [PubMed]
[4] Krammer, F., Smith, G.J.D., Fouchier, R.A.M., et al. (2018) Influenza. Nature Reviews Disease Primers, 4, Article No. 3. [Google Scholar] [CrossRef] [PubMed]
[5] Chen, J., Wang, J., Zhang, J., et al. (2021) Advances in Development and Application of Influenza Vaccines. Frontiers in Immunology, 12, Article 711997. [Google Scholar] [CrossRef] [PubMed]
[6] Nachbagauer, R. and Krammer, F. (2017) Universal Influenza Virus Vaccines and Therapeutic Antibodies. Clinical Microbiology and Infection, 23, 222-8. [Google Scholar] [CrossRef] [PubMed]
[7] Nayak, D., Shivakoti, S., Balogun, R.A., et al. (2013) Structure, Disassembly, Assembly, and Budding of Influenza Viruses. In: Webster, R.G., Arnold, S., Thomas, J., et al., Eds., Textbook of Influenza, John Wiley & Sons, Inc., Hoboken, 35-56. [Google Scholar] [CrossRef] 
[8] Paules, C.I., Marston, H.D., Eisinger, R.W., et al. (2017) The Pathway to a Universal Influenza Vaccine. Immunity, 47, 599-603. [Google Scholar] [CrossRef] [PubMed]
[9] Ng, S., Nachbagauer, R., Balmaseda, A., et al. (2019) Novel Correlates of Protection Against Pandemic H1N1 Influenza A Virus Infection. Nature Medicine, 25, 962-967. [Google Scholar] [CrossRef] [PubMed]
[10] Nuwarda, R.F., Alharbi, A.A. and Kayser, V. (2021) An Overview of Influenza Viruses and Vaccines. Vaccines, 9, Article 1032. [Google Scholar] [CrossRef] [PubMed]
[11] Hutchinson, E.C. (2018) Influenza Virus. Trends in Microbiology, 26, 809-810. [Google Scholar] [CrossRef] [PubMed]
[12] Hai, R., Krammer, F., Tan, G.S., et al. (2012) Influenza Viruses Expressing Chimeric Hemagglutinins: Globular Head and Stalk Domains Derived from Different Subtypes. Journal of Virology, 86, 5774-5781. [Google Scholar] [CrossRef] 
[13] Wu, N.C. and Wilson, I.A. (2020) Influenza Hemagglutinin Structures and Antibody Recognition. Cold Spring Harbor Perspectives in Medicine, 10, a038778. [Google Scholar] [CrossRef] [PubMed]
[14] Wang, W.C., Sayedahmed, E.E., Sambhara, S., et al. (2022) Progress towards the Development of a Universal Influenza Vaccine. Viruses, 14, Article 1684. [Google Scholar] [CrossRef] [PubMed]
[15] Krammer, F. and Palese, P. (2019) Universal Influenza Virus Vaccines That Target the Conserved Hemagglutinin Stalk and Conserved Sites in the Head Domain. The Journal of Infectious Diseases, 219, S62-S67. [Google Scholar] [CrossRef] [PubMed]
[16] Boyoglu-Barnum, S., Hutchinson, G.B., Boyington, J.C., et al. (2020) Glycan Repositioning of Influenza Hemagglutinin Stem Facilitates the Elicitation of Protective Cross-Group Antibody Responses. Nature Communications, 11, Article No. 791. [Google Scholar] [CrossRef] [PubMed]
[17] Eggink, D., Goff, P.H. and Palese, P. (2014) Guiding the Immune Response against Influenza Virus Hemagglutinin toward the Conserved Stalk Domain by Hyperglycosylation of the Globular Head Domain. Journal of Virology, 88, 699-704. [Google Scholar] [CrossRef] 
[18] De Jong, N.M.C., Aartse, A., Van Gils, M.J., et al. (2020) Development of Broadly Reactive Influenza Vaccines by Targeting the Conserved Regions of the Hemagglutinin Stem and Head Domains. Expert Review of Vaccines, 19, 563-577. [Google Scholar] [CrossRef] [PubMed]
[19] Nachbagauer, R. and Palese, P. (2020) Is a Universal Influenza Virus Vaccine Possible? Annual Review of Medicine, 71, 315-327. [Google Scholar] [CrossRef] [PubMed]
[20] Impagliazzo, A., Milder, F., Kuipers, H., et al. (2015) A Stable Trimeric Influenza Hemagglutinin Stem as a Broadly Protective Immunogen. Science, 349, 1301-1306. [Google Scholar] [CrossRef] [PubMed]
[21] Andrews, S.F., Cominsky, L.Y., Shimberg, G.D., et al. (2023) An Influenza H1 Hemagglutinin Stem-Only Immunogen Elicits a Broadly Cross-Reactive B Cell Response in Humans. Science Translational Medicine, 15, eade4976. [Google Scholar] [CrossRef] [PubMed]
[22] Corbett, K.S., Moin, S.M., Yassine, H.M., et al. (2019) Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages. mBio, 10, e02810-18. [Google Scholar] [CrossRef] 
[23] Darricarrère, N., Qiu, Y., Kanekiyo, M., et al. (2021) Broad Neutralization of H1 and H3 Viruses by Adjuvanted Influenza HA Stem Vaccines in Nonhuman Primates. Science Translational Medicine, 13, eabe5449. [Google Scholar] [CrossRef] [PubMed]
[24] Liu, W.C., Nachbagauer, R., Stadlbauer, D., et al. (2019) Sequential Immunization with Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity against Influenza A Viruses in a Preclinical Ferret Model. Frontiers in Immunology, 10, Article 756. [Google Scholar] [CrossRef] [PubMed]
[25] Nachbagauer, R., Liu, W.C., Choi, A., et al. (2017) A Universal Influenza Virus Vaccine Candidate Confers Protection against Pandemic H1N1 Infection in Preclinical Ferret Studies. NPJ Vaccines, 2, Article No. 26. [Google Scholar] [CrossRef] [PubMed]
[26] Nachbagauer, R., Feser, J., Naficy, A., et al. (2021) A Chimeric Hemagglutinin-Based Universal Influenza Virus Vaccine Approach Induces Broad and Long-Lasting Immunity in a Randomized, Placebo-Controlled Phase I Trial. Nature Medicine, 27, 106-114. [Google Scholar] [CrossRef] [PubMed]
[27] Sun, W., Kirkpatrick, E., Ermler, M., et al. (2019) Development of Influenza B Universal Vaccine Candidates Using the “Mosaic” Hemagglutinin Approach. Journal of Virology, 93, e00333-19. [Google Scholar] [CrossRef] 
[28] Allen, J.D. and Ross, T.M. (2022) Bivalent H1 and H3 COBRA Recombinant Hemagglutinin Vaccines Elicit Seroprotective Antibodies against H1N1 and H3N2 Influenza Viruses from 2009 to 2019. Journal of Virology, 96, e0165221. [Google Scholar] [CrossRef] [PubMed]
[29] Nunez, I.A., Huang, Y. and Ross, T.M. (2021) Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections. Pathogens, 10, Article 1352. [Google Scholar] [CrossRef] [PubMed]
[30] Kanekiyo, M., Joyce, M.G., Gillespie, R.A., et al. (2019) Mosaic Nanoparticle Display of Diverse Influenza Virus Hemagglutinins Elicits Broad B Cell Responses. Nature Immunology, 20, 362-372. [Google Scholar] [CrossRef] [PubMed]
[31] Al-Halifa, S., Gauthier, L., Arpin, D., et al. (2019) Nanoparticle-Based Vaccines against Respiratory Viruses. Frontiers in Immunology, 10, Article 22. [Google Scholar] [CrossRef] [PubMed]
[32] Stadlbauer, D., Zhu, X., Mcmahon, M., et al. (2019) Broadly Protective Human Antibodies That Target the Active Site of Influenza Virus Neuraminidase. Science, 366, 499-504. [Google Scholar] [CrossRef] [PubMed]
[33] Kallewaard, N.L., Corti, D., Collins, P.J., et al. (2016) Structure and Function Analysis of an Antibody Recognizing All Influenza a Subtypes. Cell, 166, 596-608. [Google Scholar] [CrossRef] [PubMed]
[34] Jiao, C., Wang, B., Chen, P., et al. (2023) Analysis of the Conserved Protective Epitopes of Hemagglutinin on Influenza A Viruses. Frontiers in Immunology, 14, Article 1086297. [Google Scholar] [CrossRef] [PubMed]
[35] Corti, D., Cameroni, E., Guarino, B., et al. (2017) Tackling Influenza with Broadly Neutralizing Antibodies. Current Opinion in Virology, 24, 60-69. [Google Scholar] [CrossRef] [PubMed]
[36] Bernstein, D.I., Guptill, J., Naficy, A., et al. (2020) Immunogenicity of Chimeric Haemagglutinin-Based, Universal Influenza Virus Vaccine Candidates: Interim Results of a Randomised, Placebo-Controlled, Phase 1 Clinical Trial. The Lancet Infectious Diseases, 20, 80-91. [Google Scholar] [CrossRef] 
[37] Liu, W.C., Nachbagauer, R., Stadlbauer, D., et al. (2021) Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model. Vaccines, 9, Article 40. [Google Scholar] [CrossRef] [PubMed]

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