1932

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. Of these, messenger RNA (mRNA) vaccines have emerged as lead candidates due to their speed of development and high degree of safety and efficacy. To date, two mRNA vaccines have received approval for human use, providing proof of the feasibility of this next-generation vaccine modality. This review gives a detailed overview about the types of mRNA vaccines developed for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview about immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform.

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2022-01-27
2024-05-21
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Literature Cited

  1. 1. 
    Krammer F. 2020. SARS-CoV-2 vaccines in development. Nature 586:516–27
    [Google Scholar]
  2. 2. 
    Wouters OJ, Shadlen KC, Salcher-Konrad M et al. 2021. Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment. Lancet 397:1023–34
    [Google Scholar]
  3. 3. 
    Pardi N, Hogan MJ, Porter FW, Weissman D. 2018. mRNA vaccines—a new era in vaccinology. Nat. Rev. Drug. Discov. 17:261–79
    [Google Scholar]
  4. 4. 
    Pardi N, Hogan MJ, Weissman D. 2020. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 65:14–20
    [Google Scholar]
  5. 5. 
    Polack FP, Thomas SJ, Kitchin N et al. 2020. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383:2603–15
    [Google Scholar]
  6. 6. 
    Baden LR, El Sahly HM, Essink B et al. 2021. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384:403–16
    [Google Scholar]
  7. 7. 
    Dagan N, Barda N, Kepten E et al. 2021. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N. Engl. J. Med. 384:1412–23
    [Google Scholar]
  8. 8. 
    Thomas SJ, Moreira ED Jr., Kitchin N et al. 2021. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months. N. Engl. J. Med. 385:176173
    [Google Scholar]
  9. 9. 
    Dai L, Gao GF. 2021. Viral targets for vaccines against COVID-19. Nat. Rev. Immunol. 21:73–82
    [Google Scholar]
  10. 10. 
    Pallesen J, Wang N, Corbett KS et al. 2017. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. PNAS 114:E7348–57
    [Google Scholar]
  11. 11. 
    Alameh MG, Weissman D, Pardi N. 2020. Messenger RNA-based vaccines against infectious diseases. Curr. Top. Microbiol. Immunol. https://doi.org/10.1007/82_2020_202
    [Crossref] [Google Scholar]
  12. 12. 
    Moderna 2021. Moderna reports second quarter fiscal year 2021 financial results and provides business updates Press Release, Aug. 5 Moderna Cambridge, MA: https://investors.modernatx.com/news-releases/news-release-details/moderna-reports-second-quarter-fiscal-year-2021-financial
  13. 13. 
    Kremsner PG, Guerrero RAA, Arana E et al. 2021. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate: results from Herald, a phase 2b/3, randomised, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. Preprint with The Lancet. http://dx.doi.org/10.2139/ssrn.3911826
    [Crossref] [Google Scholar]
  14. 14. 
    FDA 2021. FDA approves first COVID-19 vaccine. News Release Aug. 23, US Food Drug Adm Silver Spring, MD: https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine
    [Google Scholar]
  15. 15. 
    Mulligan MJ, Lyke KE, Kitchin N et al. 2020. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586:589–93
    [Google Scholar]
  16. 16. 
    Sahin U, Muik A, Derhovanessian E et al. 2020. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586:594–99
    [Google Scholar]
  17. 17. 
    Walsh EE, Frenck RW Jr., Falsey AR et al. 2020. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383:2439–50
    [Google Scholar]
  18. 18. 
    Corbett KS, Edwards DK, Leist SR et al. 2020. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 586:567–71
    [Google Scholar]
  19. 19. 
    Corbett KS, Flynn B, Foulds KE et al. 2020. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. 383:1544–55
    [Google Scholar]
  20. 20. 
    Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. 2020. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat. Microbiol. 5:1185–91
    [Google Scholar]
  21. 21. 
    Jackson LA, Anderson EJ, Rouphael NG et al. 2020. An mRNA vaccine against SARS-CoV-2—preliminary report. N. Engl. J. Med. 383:1920–31
    [Google Scholar]
  22. 22. 
    Anderson EJ, Rouphael NG, Widge AT et al. 2020. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N. Engl. J. Med. 383:2427–38
    [Google Scholar]
  23. 23. 
    Tarke A, Sidney J, Methot N et al. 2021. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell Rep. Med. 2:100355
    [Google Scholar]
  24. 24. 
    Moderna 2021. Moderna provides clinical and supply updates on COVID-19 vaccine program ahead of 2nd annual Vaccines Day News Release, Apr. 13 Moderna Cambridge, MA: https://investors.modernatx.com/node/11586/pdf
  25. 25. 
    Doria-Rose N, Suthar MS, Makowski M et al. 2021. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19. N. Engl. J. Med. 384:2259–61
    [Google Scholar]
  26. 26. 
    Pegu A, O'Connell SE, Schmidt SD et al. 2021. Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants. Science 373:1372–77
    [Google Scholar]
  27. 27. 
    Basta NEMoodie EMM (McGill Univ. COVID-19 Vaccine Tracker Team) 2020. COVID-19 vaccine development and approvals tracker. Accessed Sep. 26, 2021. https://covid19.trackvaccines.org/agency/who
  28. 28. 
    Liu Y, Liu J, Xia H et al. 2021. Neutralizing activity of BNT162b2-elicited serum. N. Engl. J. Med. 384:1466–68
    [Google Scholar]
  29. 29. 
    Muik A, Wallisch AK, Sanger B et al. 2021. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. Science 371:1152–53
    [Google Scholar]
  30. 30. 
    Sahin U, Muik A, Vogler I et al. 2021. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature 595:572–77
    [Google Scholar]
  31. 31. 
    Vogel AB, Kanevsky I, Che Y et al. 2021. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature 592:283–89
    [Google Scholar]
  32. 32. 
    Pfizer 2021. Second quarter 2021 earnings teleconference July 28. https://s21.q4cdn.com/317678438/files/doc_financials/2021/q2/Q2-2021-Earnings-Charts-FINAL.pdf
  33. 33. 
    Wang Z, Schmidt F, Weisblum Y et al. 2021. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592:616–22
    [Google Scholar]
  34. 34. 
    Steensels D, Pierlet N, Penders J et al. 2021. Comparison of SARS-CoV-2 antibody response following vaccination with BNT162b2 and mRNA-1273. JAMA 326:153335
    [Google Scholar]
  35. 35. 
    Self WH, Tenforde MW, Rhoads JP et al. 2021. Comparative effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) vaccines in preventing COVID-19 hospitalizations among adults without immunocompromising conditions—United States, March–August 2021. Morb. Mortal. Wkly. Rep. 70:1337–43
    [Google Scholar]
  36. 36. 
    Thess A, Grund S, Mui BL et al. 2015. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol. Ther. 23:1456–64
    [Google Scholar]
  37. 37. 
    Rauch S, Roth N, Schwendt K et al. 2021. mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. NPJ Vaccines 6:57
    [Google Scholar]
  38. 38. 
    Rauch S, Gooch K, Hall Y et al. 2021. mRNA vaccine CVnCoV protects non-human primates from SARS-CoV-2 challenge infection. bioRxiv 424138. https://doi.org/10.1101/2020.12.23.424138
    [Crossref]
  39. 39. 
    Kremsner P, Mann P, Bosch J et al. 2021. Phase 1 assessment of the safety and immunogenicity of an mRNA–lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers.. medRxiv 20228551. https://doi.org/10.1101/2020.11.09.20228551
    [Crossref]
  40. 40. 
    Zhang NN, Li XF, Deng YQ et al. 2020. A thermostable mRNA vaccine against COVID-19. Cell 182:1271–83.e16
    [Google Scholar]
  41. 41. 
    Kalnin KV, Plitnik T, Kishko M et al. 2021. Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models. NPJ Vaccines 6:61
    [Google Scholar]
  42. 42. 
    Sanofi Pasteur 2021. Sanofi and Translate Bio initiate phase 1/2 clinical trial of mRNA COVID-19 vaccine candidate Press Release, Mar. 12, Sanofi Pasteur, Lyon, France. https://www.sanofi.com/en/media-room/press-releases/2021/2021-03-12-07-00-00-2191846
  43. 43. 
    McKay PF, Hu K, Blakney AK et al. 2020. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat. Commun. 11:3523
    [Google Scholar]
  44. 44. 
    de Alwis R, Gan ES, Chen S et al. 2021. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Mol. Ther. 29:1970–83
    [Google Scholar]
  45. 45. 
    Arcturus Therapeutics 2020. Arcturus Therapeutics received approval from Singapore Health Sciences Authority to proceed with phase 2 study of ARCT-021 (LUNAR-COV19) vaccine candidate and provides new and updated clinical and preclinical data News Release, Dec. 28 Arcturus Therapeutics San Diego, CA: https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-received-approval-singapore-health
  46. 46. 
    Khoury DS, Cromer D, Reynaldi A et al. 2021. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27:1205–11
    [Google Scholar]
  47. 47. 
    Gilbert PB, Montefiori DC, McDermott A et al. 2021. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy trial. medRxiv 2021.08.09.21261290. https://doi.org/10.1101/2021.08.09.21261290
    [Crossref]
  48. 48. 
    Baum A, Ajithdoss D, Copin R et al. 2020. REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 370:1110–15
    [Google Scholar]
  49. 49. 
    McMahan K, Yu J, Mercado NB et al. 2021. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 590:630–34
    [Google Scholar]
  50. 50. 
    Tortorici MA, Beltramello M, Lempp FA et al. 2020. Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Science 370:950–57
    [Google Scholar]
  51. 51. 
    Laczko D, Hogan MJ, Toulmin SA et al. 2020. A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice. Immunity 53:724–32
    [Google Scholar]
  52. 52. 
    Pardi N, Hogan MJ, Pelc RS et al. 2017. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543:248–51
    [Google Scholar]
  53. 53. 
    Pardi N, Hogan MJ, Naradikian MS et al. 2018. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215:1571–88
    [Google Scholar]
  54. 54. 
    Bahl K, Senn JJ, Yuzhakov O et al. 2017. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol. Ther. 25:1316–27
    [Google Scholar]
  55. 55. 
    Pardi N, Parkhouse K, Kirkpatrick E et al. 2018. Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Nat. Commun. 9:3361
    [Google Scholar]
  56. 56. 
    Richner JM, Himansu S, Dowd KA et al. 2017. Modified mRNA vaccines protect against Zika virus infection. Cell 168:1114–25.e10
    [Google Scholar]
  57. 57. 
    Lindgren G, Ols S, Liang F et al. 2017. Induction of robust B cell responses after influenza mRNA vaccination is accompanied by circulating hemagglutinin-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells. Front. Immunol. 8:1539
    [Google Scholar]
  58. 58. 
    Lederer K, Castano D, Gomez Atria D et al. 2020. SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation. Immunity 53:1281–95
    [Google Scholar]
  59. 59. 
    Bettini E, Locci M. 2021. SARS-CoV-2 mRNA vaccines: immunological mechanism and beyond. Vaccines 9:147
    [Google Scholar]
  60. 60. 
    Karikó K, Buckstein M, Ni H, Weissman D. 2005. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23:165–75
    [Google Scholar]
  61. 61. 
    Anderson BR, Muramatsu H, Jha BK et al. 2011. Nucleoside modifications in RNA limit activation of 2′-5′-oligoadenylate synthetase and increase resistance to cleavage by RNase L.. Nucleic Acids Res 39:9329–38
    [Google Scholar]
  62. 62. 
    Anderson BR, Muramatsu H, Nallagatla SR et al. 2010. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res 38:5884–92
    [Google Scholar]
  63. 63. 
    Karikó K, Muramatsu H, Welsh FA et al. 2008. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16:1833–40
    [Google Scholar]
  64. 64. 
    Karikó K, Muramatsu H, Keller JM, Weissman D. 2012. Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin. Mol. Ther. 20:948–53
    [Google Scholar]
  65. 65. 
    Andries O, Mc Cafferty S, De Smedt SC et al. 2015. N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Control Release 217:337–44
    [Google Scholar]
  66. 66. 
    Tam HH, Melo MB, Kang M et al. 2016. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination. PNAS 113:E6639–48
    [Google Scholar]
  67. 67. 
    Vinuesa CG, Linterman MA, Yu D, MacLennan IC 2016. Follicular helper T cells. Annu. Rev. Immunol. 34:335–68
    [Google Scholar]
  68. 68. 
    Karikó K, Muramatsu H, Ludwig J, Weissman D 2011. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res 39:e142
    [Google Scholar]
  69. 69. 
    Baiersdorfer M, Boros G, Muramatsu H et al. 2019. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol. Ther. Nucleic Acids 15:26–35
    [Google Scholar]
  70. 70. 
    Pardi N, Tuyishime S, Muramatsu H et al. 2015. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control Release 217:345–51
    [Google Scholar]
  71. 71. 
    Buschmann MD, Carrasco MJ, Alishetty S et al. 2021. Nanomaterial delivery systems for mRNA vaccines. Vaccines 9:65
    [Google Scholar]
  72. 72. 
    Hassett KJ, Benenato KE, Jacquinet E et al. 2019. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol. Ther. Nucleic Acids 15:1–11
    [Google Scholar]
  73. 73. 
    Swaminathan G, Thoryk EA, Cox KS et al. 2016. A novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens. Vaccine 34:110–19
    [Google Scholar]
  74. 74. 
    Swaminathan G, Thoryk EA, Cox KS et al. 2016. A tetravalent sub-unit dengue vaccine formulated with ionizable cationic lipid nanoparticle induces significant immune responses in rodents and non-human primates. Sci. Rep. 6:34215
    [Google Scholar]
  75. 75. 
    Tanaka T, Legat A, Adam E et al. 2008. DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4. Eur. J. Immunol. 38:1351–57
    [Google Scholar]
  76. 76. 
    Lonez C, Bessodes M, Scherman D et al. 2014. Cationic lipid nanocarriers activate Toll-like receptor 2 and NLRP3 inflammasome pathways. Nanomedicine 10:775–82
    [Google Scholar]
  77. 77. 
    Holm CK, Jensen SB, Jakobsen MR et al. 2012. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat. Immunol. 13:737–43
    [Google Scholar]
  78. 78. 
    Ndeupen S, Qin Z, Jacobsen S, Estanbouli H et al. 2021. The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. bioRxiv 430128. https://doi.org/10.1101/2021.03.04.430128
    [Crossref]
  79. 79. 
    Lutz J, Lazzaro S, Habbeddine M et al. 2017. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. NPJ Vaccines 2:29
    [Google Scholar]
  80. 80. 
    Liang F, Lindgren G, Lin A et al. 2017. Efficient targeting and activation of antigen-presenting cells in vivo after modified mRNA vaccine administration in rhesus macaques. Mol. Ther. 25:2635–47
    [Google Scholar]
  81. 81. 
    Thompson MG, Burgess JL, Naleway AL et al. 2021. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers—eight U.S. locations, December 2020–March 2021. Morb. Mortal. Wkly. Rep. 70:495–500
    [Google Scholar]
  82. 82. 
    Puranik A, Lenehan PJ, Silvert E et al. 2021. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv 2021.08.06.21261707. https://doi.org/10.1101/2021.08.06.21261707
    [Crossref]
  83. 83. 
    Goldberg Y, Mandel M, Bar-On YM et al. 2021. Waning immunity of the BNT162b2 vaccine: a nationwide study from Israel. medRxiv 2021.08.24.21262423. https://doi.org/10.1101/2021.08.24.21262423
    [Crossref]
  84. 84. 
    Antonelli M, Penfold RS, Merino J et al. 2021. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect. Dis. In press. https://doi.org/10.1016/S1473-3099(21)00460-6
    [Crossref] [Google Scholar]
  85. 85. 
    Planas D, Veyer D, Baidaliluk A et al. 2021. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596:276–80
    [Google Scholar]
  86. 86. 
    Mlcochova P, Kemp S, Dhar MS et al. 2021. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature 599:11419
    [Google Scholar]
  87. 87. 
    Lopez Bernal J, Andrews N, Gower C et al. 2021. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. N. Engl. J. Med. 385:585–94
    [Google Scholar]
  88. 88. 
    Pouwels KB, Pritchard E, Matthews PC et al. 2021. Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK Work. Pap. Nuffield Dep. Med., Univ. Oxford Oxford, UK: https://www.ndm.ox.ac.uk/files/coronavirus/covid-19-infection-survey/finalfinalcombinedve20210816.pdf
  89. 89. 
    Wu K, Choi A, Koch M et al. 2021. Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice. bioRxiv 439482. https://doi.org/10.1101/2021.04.13.439482
    [Crossref]
  90. 90. 
    Moderna 2021. Moderna announces significant advances across industry-leading mRNA portfolio at 2021 R&D Day Press Release, Sep. 9 Moderna Cambridge, MA: https://investors.modernatx.com/node/12801/pdf
  91. 91. 
    Shimabukuro TT, Cole M, Su JR. 2021. Reports of anaphylaxis after receipt of mRNA COVID-19 vaccines in the US—December 14, 2020–January 18, 2021. JAMA 325:1101–2
    [Google Scholar]
  92. 92. 
    Klein NP, Lewis N, Goddard K et al. 2021. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA 326:139099
    [Google Scholar]
  93. 93. 
    Mohamed M, Abu Lila AS, Shimizu T et al. 2019. PEGylated liposomes: immunological responses. Sci. Technol. Adv. Mater. 20:710–24
    [Google Scholar]
  94. 94. 
    Gargano JW, Wallace M, Hadler SC et al. 2021. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021. Morb. Mortal. Wkly. Rep. 70:977–82
    [Google Scholar]
  95. 95. 
    Doria-Rose N, Suthar MS, Makowski M et al. 2021. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19. N. Engl. J. Med. 384:2259–61
    [Google Scholar]
  96. 96. 
    Skjefte M, Ngirbabul M, Akeju O et al. 2021. COVID-19 vaccine acceptance among pregnant women and mothers of young children: results of a survey in 16 countries. Eur. J. Epidemiol. 36:197–211
    [Google Scholar]
  97. 97. 
    Allotey J, Stallings E, Bonet M et al. 2020. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 370:m3320
    [Google Scholar]
  98. 98. 
    Frenck RW, Klein NP, Kitchin N et al. 2021. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N. Engl. J. Med. 385:239–50
    [Google Scholar]
  99. 99. 
    Moderna 2021. Moderna announces TeenCOVE study of its COVID-19 vaccine in adolescents meets primary endpoint and plans to submit data to regulators in early June Press Release, May 25 Moderna Cambridge, MA: https://investors.modernatx.com/node/12031/pdf
  100. 100. 
    Pfizer 2021. Pfizer and BioNTech announce positive topline results from pivotal trial of Covid-19 vaccine in children 5 to 11 years News Release, Sep. 20 Pfizer New York, NY: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-positive-topline-results
  101. 101. 
    Gray KJ, Bordt EA, Atyeo C et al. 2021. COVID-19 vaccine response in pregnant and lactating women: a cohort study. Am. J. Obstet. Gynecol. 225:303.e1–e17
    [Google Scholar]
  102. 102. 
    Shimabukuro TT, Kim SY, Myers TR et al. 2021. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N. Engl. J. Med. 384:2273–82
    [Google Scholar]
  103. 103. 
    Bergman P, Blennow O, Hansson L et al. 2021. Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial. medRxiv 2021.09.07.21263206. https://doi.org/10.1101/2021.09.07.21263206
    [Crossref]
  104. 104. 
    Bianchi DW, Kaeser L, Cernich AN. 2021. Involving pregnant individuals in clinical research on COVID-19 vaccines. JAMA 325:1041–42
    [Google Scholar]
  105. 105. 
    HHS (Dep. Health Hum. Serv.) 2021. Biden Administration purchases additional doses of COVID-19 vaccines from Pfizer and Moderna News Release, Feb. 11 Dep. Health Hum. Serv. Washington, DC: https://www.hhs.gov/about/news/2021/02/11/biden-administration-purchases-additional-doses-covid-19-vaccines-from-pfizer-and-moderna.html
  106. 106. 
    Pfizer 2021. Pfizer reports fourth-quarter and full-year 2020 results and releases 5-year pipeline metrics Press Release, Feb. 2 Pfizer New York, NY: https://s21.q4cdn.com/317678438/files/doc_financials/2020/q4/Q4-2020-PFE-Earnings-Release.pdf
  107. 107. 
    Duke Global Health Innov. Cent 2021. Launch and scale speedometer. Duke Univ. Accessed Apr. 2. https://launchandscalefaster.org/covid-19
  108. 108. 
    WHO 2021. Joint COVAX statement on supply forecast for 2021 and early 2022 News, World Health Organ. Geneva: https://www.who.int/news/item/08-09-2021-joint-covax-statement-on-supply-forecast-for-2021-and-early-2022
  109. 109. 
    Falsey AR, Frenck RW, Walsh EE et al. 2021. SARS-CoV-2 neutralization with BNT162b2 vaccine dose 3. N. Engl. J. Med 385:162729
    [Google Scholar]
  110. 110. 
    Moderna 2021. Moderna announces submission of initial data to U.S. FDA for its COVID-19 vaccine booster Press Release, Sep. 1 Moderna Cambridge, MA: https://investors.modernatx.com/node/12741/pdf
  111. 111. 
    Bar-On YM, Goldberg Y, Mandel M et al. 2021. Protection of BNT162b2 vaccine booster against Covid-19 in Israel. N. Engl. J. Med. 385:1393400
    [Google Scholar]
  112. 112. 
    WHO 2021. WHO Director-General's opening remarks at the media briefing on COVID-19—8 September 2021 Speech, World Health Organ. Geneva: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---8-september-2021
  113. 113. 
    Schoenmaker L, Witzigmann D, Kulkarni JA et al. 2021. mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability. Int. J. Pharm. 601:120586
    [Google Scholar]
  114. 114. 
    FDA (Food Drug Adm.) 2021. Coronavirus (COVID-19) update: FDA allows more flexible storage, transportation conditions for Pfizer-BioNTech COVID-19 vaccine Press Release, Feb. 25 US Food Drug Adm. Silver Spring, MD: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-allows-more-flexible-storage-transportation-conditions-pfizer
  115. 115. 
    Moderna 2021. First participants dosed in phase 1 study evaluating mRNA-1283, Moderna's next generation COVID-19 vaccine Press Release, Mar. 15 Moderna Cambridge, MA: https://investors.modernatx.com/news-releases/news-release-details/first-participants-dosed-phase-1-study-evaluating-mrna-1283
  116. 116. 
    Hsieh CL, Goldsmith JA, Schaub JM et al. 2020. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science 369:1501–5
    [Google Scholar]
  117. 117. 
    Krammer F. 2020. Pandemic vaccines: How are we going to be better prepared next time?. Med 1:28–32
    [Google Scholar]
  118. 118. 
    Pardi N, Secreto AJ, Shan X et al. 2017. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat. Commun. 8:14630
    [Google Scholar]
/content/journals/10.1146/annurev-med-042420-112725
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