mRNA疫苗研究进展——2021年拉斯克奖临床医学研究奖

doi:10.3969/j.issn.1006-7795.2021.05.033

摘要/Abstract

摘要： 2021年拉斯克临床医学研究奖授予在mRNA疫苗研发工作做出重大贡献的生物化学家Katalin Karikó和免疫学家Drew Weissman。然而目前对此类疫苗的了解尚不充分。mRNA疫苗是将合成的编码蛋白质抗原的mRNA序列递送至体内指导机体表达相应的蛋白质,并诱导机体产生针对该蛋白的免疫应答以实现疾病预防和治疗的目的。mRNA 疫苗作为一种新型的核酸疫苗,具有高转染效率、强免疫刺激能力、良好的安全性、易产业化和低成本等特点,mRNA疫苗在传染病和肿瘤的预防和治疗应用中展示了其特有的优势。

关键词: mRNA疫苗, 感染性疾病, 肿瘤, 临床试验

Abstract: The 2021 Lasker Clinical Medicine Research Award is awarded to biochemist Katalin Karikó and immunologist Drew Weissman who have made significant contributions to the research and development of mRNA vaccines. However, the current understanding of such vaccines is still insufficient. Messenger RNA (mRNA) vaccine is to synthesize mRNA sequence encoding a given specific antigen in vitro, which can be delivered into the body and express the corresponding protein. In turn, the antigenic protein encoded by the mRNA vaccine is able to induce an immune response against the specific antigen protein, which can prevent and treat a certain disease. As a new type of vaccine, mRNA vaccine has the characteristics of high transfectional efficiency, strong ability for immune stimulation, good safety, rapid industrialization and low cost, etc. The application of mRNA vaccine in the prevention and theraputis of some infectious diseases and cancers has shown its unique advantages.

Key words: mRNA vaccine, infectious diseases, tumor, clinical trials

中图分类号:

Q522⁺.2

陈彦, 孙英. mRNA疫苗研究进展——2021年拉斯克奖临床医学研究奖[J]. 首都医科大学学报, 2021, 42(5): 893-889.

Chen Yan, Sun Ying. Progress in mRNA vaccine—The 2021 Lasker Clinical Medicine Research Award[J]. Journal of Capital Medical University, 2021, 42(5): 893-889.

参考文献

[1] The Lasker Awards. Modified mRNA vaccines 2021 Lasker~DeBakey Clinical Medical Research Award[EB/OL].(2021-09-24)[2021-10-04].https://laskerfoundation.org/winners/modified-mrna-vaccines/.
[2] Malone R W, Felgner P L, Verma I M. Cationic liposome-mediated RNA transfection[J]. Proc Natl Acad Sci U S A, 1989, 86(16): 6077-6081.
[3] Wolff J A, Malone R W, Williams P, et al. Direct gene transfer into mouse muscle in vivo[J]. Science, 1990, 247(4949Pt1): 1465-1468.
[4] Kariko K, Ni H, Capodici J, et al. mRNA is an endogenous ligand for Toll-like receptor 3[J]. J Biol Chem, 2004, 279: 12542-12550
[5] Kariko K, Buckstein M, Ni H, et al. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA[J]. Immunity, 2005, 23(2): 165-175.
[6] Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer[J]. Nature,2017, 547(7662): 222-226.
[7] Anderson E J, Rouphael N G, Widge A T, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults[J]. N Engl J Med, 2020, 383(25): 2427-2438.
[8] Holtkamp S, Kreiter S, Selmi A, et al. Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells[J]. Blood, 2006, 108(13): 4009-4017.
[9] Kowalski P S, Rudra A, Miao L, et al. Delivering the messenger: advances in technologies for therapeutic mRNA delivery[J]. Mol Ther, 2019, 27(4): 710-728.
[10]De Beuckelaer A, Grooten J, De Koker S. Type I interferons modulate CD8(+) T cell immunity to mRNA vaccines[J]. Trends Mol Med, 2017, 23(3): 216-226.
[11]Linares-Fernandez S, Lacroix C, Exposito J Y, et al. Tailoring mRNA vaccine to balance innate/adaptive immune response[J]. Trends Mol Med, 2020, 26(3): 311-323.
[12]Wadhwa A, Aljabbari A, Lokras A, et al. Opportunities and challenges in the delivery of mRNA-based vaccines[J]. Pharmaceutics, 2020, 12(2):102.
[13]Khoury H J, Collins R H, Blum W, et al. Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia[J]. Cancer, 2017, 123(16): 3061-3072.
[14]Banchereau J, Palucka A K. Dendritic cells as therapeutic vaccines against cancer[J]. Nat Rev Immunol, 2005, 5(4): 296-306.
[15]Alberer M, Gnad-Vogt U, Hong H S, et al. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial[J]. Lancet, 2017, 390(10101): 1511-1520.
[16]Sebastian M, Schroder A, Scheel B, et al. A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer[J]. Cancer Immunol Immunother, 2019, 68(5): 799-812.
[17]Geall A J, Verma A, Otten G R, et al. Nonviral delivery of self-amplifying RNA vaccines[J]. Proc Natl Acad Sci U S A, 2012, 109(36): 14604-14609.
[18]Xu S, Yang K, Li R, et al. mRNA vaccine era-mechanisms, drug platform and clinical prospection[J]. Int J Mol Sci, 2020, 21(18):6582.
[19]Petsch B, Schnee M, Vogel A B, et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection[J]. Nat Biotechnol, 2012, 30(12): 1210-1216.
[20]Feldman R A, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials[J]. Vaccine, 2019, 37(25): 3326-3334.
[21]Meyer M, Huang E, Yuzhakov O, et al. Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease[J]. J Infect Dis, 2018, 217(3): 451-455.
[22]Roth C, Cantaert T, Colas C, et al. A modified mRNA vaccine targeting immunodominant NS epitopes protects against dengue virus infection in HLA class I transgenic mice[J]. Front Immunol, 2019, 10: 1424.
[23]Pardi N, Hogan M J, Pelc R S, et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination[J]. Nature, 2017, 543(7644): 248-251.
[24]Schnee M, Vogel A B, Voss D, et al. An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs[J]. PLoS Negl Trop Dis, 2016, 10: e0004746
[25]Van Craenenbroeck A H, Smits E L, Anguille S, et al. Induction of cytomegalovirus-specific T cell responses in healthy volunteers and allogeneic stem cell recipients using vaccination with messenger RNA-transfected dendritic cells[J]. Transplantation, 2015, 99(1): 120-127.
[26]Polack F P, Thomas S J, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine[J]. N Engl J Med, 2020, 383: 2603-2615.
[27]Conry R M, LoBuglio A F, Wright M, et al. Characterization of a messenger RNA polynucleotide vaccine vector[J]. Cancer Res, 1995, 55(7): 1397-1400.
[28]Phua K K, Boczkowski D, Dannull J, et al. Whole blood cells loaded with messenger RNA as an anti-tumor vaccine[J]. Adv Health Mater, 2014, 3(6): 837-842.
[29]Jindal V, Arora E, Gupta S, et al. Prospects of chimeric antigen receptor T cell therapy in ovarian cancer[J]. Med Oncol, 2018, 35(5): 70.
[30]Reinhard K, Rengstl B, Oehm P, et al. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors[J]. Science, 2020, 367(6476): 446-453.
[31]Hobo W, Novobrantseva T I, Fredrix H, et al. Improving dendritic cell vaccine immunogenicity by silencing PD-1 ligands using siRNA-lipid nanoparticles combined with antigen mRNA electroporation[J]. Cancer Immunol Immunother,2013, 62(2): 285-297.
[32]Lorenzi J C, Trombone A P, Rocha C D, et al. Intranasal vaccination with messenger RNA as a new approach in gene therapy: use against tuberculosis[J]. BMC Biotechnol,2010, 10: 77.
[33]Baeza G A, Siu E, Sun T, et al. Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection[J]. Nat Commun, 2018, 9(1): 2714.
[34]Krienke C, Kolb L, Diken E, et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis[J]. Science, 2021, 371(6525): 145-153.