IMMUNE NETWORK

  • 제24권4호
  • /
  • Pages.28.1-28.13
  • /
  • 2024
  • /
  • 1598-2629(pISSN)
  • /
  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지
DOI QR코드

DOI QR Code

Germinal Center Response to mRNA Vaccination and Impact of Immunological Imprinting on Subsequent Vaccination

  • Wooseob Kim (Department of Microbiology, Korea University College of Medicine)
  • 투고 : 2024.01.30
  • 심사 : 2024.04.29
  • 발행 : 2024.08.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Vaccines are the most effective intervention currently available, offering protective immunity against targeted pathogens. The emergence of the coronavirus disease 2019 pandemic has prompted rapid development and deployment of lipid nanoparticle encapsulated, mRNA-based vaccines. While these vaccines have demonstrated remarkable immunogenicity, concerns persist regarding their ability to confer durable protective immunity to continuously evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. This review focuses on human B cell responses induced by SARS-CoV-2 mRNA vaccination, with particular emphasis on the crucial role of germinal center reactions in shaping enduring protective immunity. Additionally, we explored observations of immunological imprinting and dynamics of recalled pre-existing immunity following variants of concern-based booster vaccination. Insights from this review contribute to comprehensive understanding B cell responses to mRNA vaccination in humans, thereby refining vaccination strategies for optimal and sustained protection against evolving coronavirus variants.

키워드

참고문헌

  1. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, Zhang Q, Shi X, Wang Q, Zhang L, et al. Structure of the SARSCoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020;581:215-220. https://doi.org/10.1038/s41586-020-2180-5
  2. Barouch DH. COVID-19 vaccines - immunity, variants, boosters. N Engl J Med 2022;387:1011-1020. https://doi.org/10.1056/NEJMra2206573
  3. Dashdorj NJ, Wirz OF, Roltgen K, Haraguchi E, Buzzanco AS 3rd, Sibai M, Wang H, Miller JA, Solis D, Sahoo MK, et al. Direct comparison of antibody responses to four SARS-CoV-2 vaccines in Mongolia. Cell Host Microbe 2021;29:1738-1743.e4.
  4. Zhang Z, Mateus J, Coelho CH, Dan JM, Moderbacher CR, Galvez RI, Cortes FH, Grifoni A, Tarke A, Chang J, et al. Humoral and cellular immune memory to four COVID-19 vaccines. Cell 2022;185:2434-2451.e17. https://doi.org/10.1016/j.cell.2022.05.022
  5. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2021;384:403-416. https://doi.org/10.1056/NEJMoa2035389
  6. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med 2020;383:2603-2615. https://doi.org/10.1056/NEJMoa2034577
  7. Slifka MK, Amanna I. How advances in immunology provide insight into improving vaccine efficacy. Vaccine 2014;32:2948-2957. https://doi.org/10.1016/j.vaccine.2014.03.078
  8. Mesin L, Ersching J, Victora GD. Germinal center B cell dynamics. Immunity 2016;45:471-482. https://doi.org/10.1016/j.immuni.2016.09.001
  9. Berek C, Berger A, Apel M. Maturation of the immune response in germinal centers. Cell 1991;67:1121-1129. https://doi.org/10.1016/0092-8674(91)90289-B
  10. Cyster JG. B cell follicles and antigen encounters of the third kind. Nat Immunol 2010;11:989-996. https://doi.org/10.1038/ni.1946
  11. Carati C, Gannon B, Piller N. Anatomy and physiology in relation to compression of the upper limb and thorax. J Lymphoedema 2010;5:58-67.
  12. Havenar-Daughton C, Newton IG, Zare SY, Reiss SM, Schwan B, Suh MJ, Hasteh F, Levi G, Crotty S. Normal human lymph node T follicular helper cells and germinal center B cells accessed via fine needle aspirations. J Immunol Methods 2020;479:112746.
  13. Lederer K, Bettini E, Parvathaneni K, Painter MM, Agarwal D, Lundgreen KA, Weirick M, Muralidharan K, Castano D, Goel RR, et al. Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals. Cell 2022;185:1008-1024.e15. https://doi.org/10.1016/j.cell.2022.01.027
  14. Mudd PA, Minervina AA, Pogorelyy MV, Turner JS, Kim W, Kalaidina E, Petersen J, Schmitz AJ, Lei T, Haile A, et al. SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans. Cell 2022;185:603-613.e15. https://doi.org/10.1016/j.cell.2021.12.026
  15. Roltgen K, Nielsen SC, Silva O, Younes SF, Zaslavsky M, Costales C, Yang F, Wirz OF, Solis D, Hoh RA, et al. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell 2022;185:1025-1040.e14. https://doi.org/10.1016/j.cell.2022.01.018
  16. Kim W, Zhou JQ, Horvath SC, Schmitz AJ, Sturtz AJ, Lei T, Liu Z, Kalaidina E, Thapa M, Alsoussi WB, et al. Germinal centre-driven maturation of B cell response to mRNA vaccination. Nature 2022;604:141-145. https://doi.org/10.1038/s41586-022-04527-1
  17. Turner JS, O'Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, Lei T, Thapa M, Chen RE, Case JB, et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 2021;596:109-113. https://doi.org/10.1038/s41586-021-03738-2
  18. Cyster JG, Allen CD. B cell responses: cell interaction dynamics and decisions. Cell 2019;177:524-540. https://doi.org/10.1016/j.cell.2019.03.016
  19. Young C, Brink R. The unique biology of germinal center B cells. Immunity 2021;54:1652-1664. https://doi.org/10.1016/j.immuni.2021.07.015
  20. Phan TG, Paus D, Chan TD, Turner ML, Nutt SL, Basten A, Brink R. High affinity germinal center B cells are actively selected into the plasma cell compartment. J Exp Med 2006;203:2419-2424. https://doi.org/10.1084/jem.20061254
  21. Krautler NJ, Suan D, Butt D, Bourne K, Hermes JR, Chan TD, Sundling C, Kaplan W, Schofield P, Jackson J, et al. Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells. J Exp Med 2017;214:1259-1267. https://doi.org/10.1084/jem.20161533
  22. Hammarlund E, Thomas A, Amanna IJ, Holden LA, Slayden OD, Park B, Gao L, Slifka MK. Plasma cell survival in the absence of B cell memory. Nat Commun 2017;8:1781.
  23. Zehentmeier S, Roth K, Cseresnyes Z, Sercan O, Horn K, Niesner RA, Chang HD, Radbruch A, Hauser AE. Static and dynamic components synergize to form a stable survival niche for bone marrow plasma cells. Eur J Immunol 2014;44:2306-2317. https://doi.org/10.1002/eji.201344313
  24. Brynjolfsson SF, Mohaddes M, Karrholm J, Wick MJ. Long-lived plasma cells in human bone marrow can be either CD19+ or CD19. Blood Adv 2017;1:835-838. https://doi.org/10.1182/bloodadvances.2017004481
  25. Mesin L, Schiepers A, Ersching J, Barbulescu A, Cavazzoni CB, Angelini A, Okada T, Kurosaki T, Victora GD. Restricted clonality and limited germinal center reentry characterize memory b cell reactivation by boosting. Cell 2020;180:92-106.e11. https://doi.org/10.1016/j.cell.2019.11.032
  26. Turner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB, Lei T, Amor M, McIntire KM, Meade P, et al. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature 2020;586:127-132.
  27. Ng KW, Faulkner N, Cornish GH, Rosa A, Harvey R, Hussain S, Ulferts R, Earl C, Wrobel AG, Benton DJ, et al. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science 2020;370:1339-1343. https://doi.org/10.1126/science.abe1107
  28. Murray SM, Ansari AM, Frater J, Klenerman P, Dunachie S, Barnes E, Ogbe A. The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses. Nat Rev Immunol 2023;23:304-316. https://doi.org/10.1038/s41577-022-00809-x
  29. Purtha WE, Tedder TF, Johnson S, Bhattacharya D, Diamond MS. Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants. J Exp Med 2011;208:2599-2606. https://doi.org/10.1084/jem.20110740
  30. Pape KA, Taylor JJ, Maul RW, Gearhart PJ, Jenkins MK, Different B. Different B cell populations mediate early and late memory during an endogenous immune response. Science 2011;331:1203-1207. https://doi.org/10.1126/science.1201730
  31. Elsner RA, Shlomchik MJ. Germinal center and extrafollicular B cell responses in vaccination, immunity, and autoimmunity. Immunity 2020;53:1136-1150. https://doi.org/10.1016/j.immuni.2020.11.006
  32. Alsoussi WB, Malladi SK, Zhou JQ, Liu Z, Ying B, Kim W, Schmitz AJ, Lei T, Horvath SC, Sturtz AJ, et al. SARS-CoV-2 Omicron boosting induces de novo B cell response in humans. Nature 2023;617:592-598.
  33. Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 2008;453:667-671. https://doi.org/10.1038/nature06890
  34. Ellebedy AH, Jackson KJ, Kissick HT, Nakaya HI, Davis CW, Roskin KM, McElroy AK, Oshansky CM, Elbein R, Thomas S, et al. Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination. Nat Immunol 2016;17:1226-1234. https://doi.org/10.1038/ni.3533
  35. Kardava L, Rachmaninoff N, Lau WW, Buckner CM, Trihemasava K, Blazkova J, Lopes de Assis F, Wang W, Zhang X, Wang Y, et al. Early human B cell signatures of the primary antibody response to mRNA vaccination. Proc Natl Acad Sci U S A 2022;119:e2204607119.
  36. Bok K, Sitar S, Graham BS, Mascola JR. Accelerated COVID-19 vaccine development: milestones, lessons, and prospects. Immunity 2021;54:1636-1651. https://doi.org/10.1016/j.immuni.2021.07.017
  37. Jung J, Kim JY, Kwon JS, Yun SC, Kim SH. Comparison of waning immunity between booster vaccination and 2-dose vaccination with BNT162b2. Immune Netw 2022;22:e31.
  38. Laidlaw BJ, Ellebedy AH. The germinal centre B cell response to SARS-CoV-2. Nat Rev Immunol 2022;22:7-18. https://doi.org/10.1038/s41577-021-00657-1
  39. Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 2021;184:861-880. https://doi.org/10.1016/j.cell.2021.01.007
  40. Krause PR, Fleming TR, Longini IM, Peto R, Briand S, Heymann DL, Beral V, Snape MD, Rees H, Ropero AM, et al. SARS-CoV-2 variants and vaccines. N Engl J Med 2021;385:179-186. https://doi.org/10.1056/NEJMsr2105280
  41. Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol 2012;30:429-457. https://doi.org/10.1146/annurev-immunol-020711-075032
  42. Alameh MG, Tombacz I, Bettini E, Lederer K, Sittplangkoon C, Wilmore JR, Gaudette BT, Soliman OY, Pine M, Hicks P, et al. Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 2021;54:2877-2892.e7. https://doi.org/10.1016/j.immuni.2021.11.001
  43. Li C, Lee A, Grigoryan L, Arunachalam PS, Scott MK, Trisal M, Wimmers F, Sanyal M, Weidenbacher PA, Feng Y, et al. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine. Nat Immunol 2022;23:543-555.
  44. Tahtinen S, Tong AJ, Himmels P, Oh J, Paler-Martinez A, Kim L, Wichner S, Oei Y, McCarron MJ, Freund EC, et al. IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines. Nat Immunol 2022;23:532-542.
  45. Hassett KJ, Rajlic IL, Bahl K, White R, Cowens K, Jacquinet E, Burke KE. mRNA vaccine trafficking and resulting protein expression after intramuscular administration. Mol Ther Nucleic Acids 2023;35:102083.
  46. Martinez-Riano A, Wang S, Boeing S, Minoughan S, Casal A, Spillane KM, Ludewig B, Tolar P. Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network. Nat Immunol 2023;24:1281-1294. https://doi.org/10.1038/s41590-023-01559-1
  47. Pikor NB, Morbe U, Lutge M, Gil-Cruz C, Perez-Shibayama C, Novkovic M, Cheng HW, Nombela-Arrieta C, Nagasawa T, Linterman MA, et al. Remodeling of light and dark zone follicular dendritic cells governs germinal center responses. Nat Immunol 2020;21:649-659. https://doi.org/10.1038/s41590-020-0672-y
  48. Cho A, Muecksch F, Schaefer-Babajew D, Wang Z, Finkin S, Gaebler C, Ramos V, Cipolla M, Mendoza P, Agudelo M, et al. Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination. Nature 2021;600:517-522. https://doi.org/10.1038/s41586-021-04060-7
  49. Sokal A, Barba-Spaeth G, Fernandez I, Broketa M, Azzaoui I, de La Selle A, Vandenberghe A, Fourati S, Roeser A, Meola A, et al. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity 2021;54:2893-2907.e5. https://doi.org/10.1016/j.immuni.2021.09.011
  50. Goel RR, Painter MM, Apostolidis SA, Mathew D, Meng W, Rosenfeld AM, Lundgreen KA, Reynaldi A, Khoury DS, Pattekar A, et al. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science 2021;374:abm0829.
  51. Pape KA, Dileepan T, Kabage AJ, Kozysa D, Batres R, Evert C, Matson M, Lopez S, Krueger PD, Graiziger C, et al. High-affinity memory B cells induced by SARS-CoV-2 infection produce more plasmablasts and atypical memory B cells than those primed by mRNA vaccines. Cell Reports 2021;37:109823.
  52. Tong P, Gautam A, Windsor IW, Travers M, Chen Y, Garcia N, Whiteman NB, McKay LG, Storm N, Malsick LE, et al. Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike. Cell 2021;184:4969-4980.e15.
  53. Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, Claer L, Quentric P, Fadlallah J, Devilliers H, Ghillani P, et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med 2021;13:eabd2223.
  54. Corthesy B. Multi-faceted functions of secretory IgA at mucosal surfaces. Front Immunol 2013;4:185.
  55. Wang Z, Lorenzi JC, Muecksch F, Finkin S, Viant C, Gaebler C, Cipolla M, Hoffmann HH, Oliveira TY, Oren DA, et al. Enhanced SARS-CoV-2 neutralization by dimeric IgA. Sci Transl Med 2021;13:eabf1555.
  56. Sheikh-Mohamed S, Sanders EC, Gommerman JL, Tal MC. Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS-CoV-2 infection. Immunol Rev 2022;309:75-85. https://doi.org/10.1111/imr.13118
  57. Hassan AO, Kafai NM, Dmitriev IP, Fox JM, Smith BK, Harvey IB, Chen RE, Winkler ES, Wessel AW, Case JB, et al. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARSCoV-2. Cell 2020;183:169-184.e13. https://doi.org/10.1016/j.cell.2020.08.026
  58. Carr EJ, Dowgier G, Greenwood D, Herman LS, Hobbs A, Ragno M, Stevenson-Leggett P, Gahir J, Townsley H, Harvey R, SARS-CoV-2 mucosal neutralising immunity after vaccination. Lancet Infect Dis 2024;24:e4-e5.
  59. McMahan K, Wegmann F, Aid M, Sciacca M, Liu J, Hachmann NP, Miller J, Jacob-Dolan C, Powers O, Hope D, et al. Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques. Nature 2024;626:385-391.
  60. Waltz E. How nasal-spray vaccines could change the pandemic. Nature 2022;609:240-242. https://doi.org/10.1038/d41586-022-02824-3
  61. Moore KA, Leighton T, Ostrowsky JT, Anderson CJ, Danila RN, Ulrich AK, Lackritz EM, Mehr AJ, Baric RS, Baylor NW, et al. A research and development (R&D) roadmap for broadly protective coronavirus vaccines: a pandemic preparedness strategy. Vaccine 2023;41:2101-2112. https://doi.org/10.1016/j.vaccine.2023.02.032
  62. Becerra X, Jha A. Project NextGen - defeating SARS-CoV-2 and preparing for the next pandemic. N Engl J Med 2023;389:773-775. https://doi.org/10.1056/NEJMp2307867
  63. Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, Schaefer-Babajew D, Cipolla M, Gaebler C, Lieberman JA, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 2021;592:616-622. https://doi.org/10.1038/s41586-021-03324-6
  64. Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, Gower C, Kall M, Groves N, O'Connell AM, et al. COVID-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N Engl J Med 2022;386:1532-1546. https://doi.org/10.1056/NEJMoa2119451
  65. Kuhlmann C, Mayer CK, Claassen M, Maponga T, Burgers WA, Keeton R, Riou C, Sutherland AD, Suliman T, Shaw ML, et al. Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose. Lancet 2022;399:625-626. https://doi.org/10.1016/S0140-6736(22)00090-3
  66. Schmidt F, Muecksch F, Weisblum Y, Da Silva J, Bednarski E, Cho A, Wang Z, Gaebler C, Caskey M, Nussenzweig MC, et al. Plasma neutralization of the SARS-CoV-2 Omicron variant. N Engl J Med 2022;386:599-601. https://doi.org/10.1056/NEJMc2119641
  67. Cele S, Jackson L, Khoury DS, Khan K, Moyo-Gwete T, Tegally H, San JE, Cromer D, Scheepers C, Amoako DG, et al. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature 2022;602:654-656.
  68. Francis T. On the doctrine of original antigenic sin. Proc Am Philos Soc 1960;104:572-578.
  69. Henry C, Palm AE, Krammer F, Wilson PC. From original antigenic sin to the universal influenza virus vaccine. Trends Immunol 2018;39:70-79. https://doi.org/10.1016/j.it.2017.08.003
  70. Koutsakos M, Ellebedy AH. Immunological imprinting: understanding COVID-19. Immunity 2023;56:909-913. https://doi.org/10.1016/j.immuni.2023.04.012
  71. Cobey S, Hensley SE. Immune history and influenza virus susceptibility. Curr Opin Virol 2017;22:105-111. https://doi.org/10.1016/j.coviro.2016.12.004
  72. Good KL, Avery DT, Tangye SG. Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells. J Immunol 2009;182:890-901.
  73. Lucas C, Vogels CB, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, et al. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021;600:523-529. https://doi.org/10.1038/s41586-021-04085-y
  74. Muecksch F, Wang Z, Cho A, Gaebler C, Ben Tanfous T, DaSilva J, Bednarski E, Ramos V, Zong S, Johnson B, et al. Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost. Nature 2022;607:128-134.
  75. Goel RR, Painter MM, Lundgreen KA, Apostolidis SA, Baxter AE, Giles JR, Mathew D, Pattekar A, Reynaldi A, Khoury DS, et al. Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine. Cell 2022;185:1875-1887.e8. https://doi.org/10.1016/j.cell.2022.04.009
  76. Arunachalam PS, Lai L, Samaha H, Feng Y, Hu M, Hui HS, Wali B, Ellis M, Davis-Gardner ME, Huerta C, et al. Durability of immune responses to mRNA booster vaccination against COVID-19. J Clin Invest 2023;133:e167955.
  77. Choi A, Koch M, Wu K, Chu L, Ma L, Hill A, Nunna N, Huang W, Oestreicher J, Colpitts T, et al. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat Med 2021;27:2025-2031. https://doi.org/10.1038/s41591-021-01527-y
  78. Zhang NN, Zhang RR, Zhang YF, Ji K, Xiong XC, Qin QS, Gao P, Lu XS, Zhou HY, Song HF, et al. Rapid development of an updated mRNA vaccine against the SARS-CoV-2 Omicron variant. Cell Res 2022;32:401-403. https://doi.org/10.1038/s41422-022-00626-w
  79. Scheaffer SM, Lee D, Whitener B, Ying B, Wu K, Liang CY, Jani H, Martin P, Amato NJ, Avena LE, et al. Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice. Nat Med 2023;29:247-257. https://doi.org/10.1038/s41591-022-02092-8
  80. Collier AY, Miller J, Hachmann NP, McMahan K, Liu J, Bondzie EA, Gallup L, Rowe M, Schonberg E, Thai S, et al. Immunogenicity of BA.5 bivalent mRNA vaccine boosters. N Engl J Med 2023;388:565-567. https://doi.org/10.1056/NEJMc2213948
  81. Nham E, Kim J, Lee J, Park H, Kim J, Lee S, Choi J, Kim KT, Yoon JG, Hwang SY, et al. Low neutralizing activities to the omicron subvariants BN.1 and XBB.1.5 of sera from the individuals vaccinated with a BA.4/5-containing bivalent mRNA vaccine. Immune Netw 2023;23:e43.
  82. Chu L, Vrbicky K, Montefiori D, Huang W, Nestorova B, Chang Y, Carfi A, Edwards DK, Oestreicher J, Legault H, et al. Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial. Nat Med 2022;28:1042-1049. https://doi.org/10.1038/s41591-022-01739-w
  83. Schiepers A, van 't Wout MF, Greaney AJ, Zang T, Muramatsu H, Lin PJ, Tam YK, Mesin L, Starr TN, Bieniasz PD, et al. Molecular fate-mapping of serum antibody responses to repeat immunization. Nature 2023;615:482-489. https://doi.org/10.1038/s41586-023-05715-3
  84. Smith DJ, Forrest S, Ackley DH, Perelson AS. Variable efficacy of repeated annual influenza vaccination. Proc Natl Acad Sci U S A 1999;96:14001-14006. https://doi.org/10.1073/pnas.96.24.14001
  85. Huang CQ, Vishwanath S, Carnell GW, Chan AC, Heeney JL. Immune imprinting and next-generation coronavirus vaccines. Nat Microbiol 2023;8:1971-1985. https://doi.org/10.1038/s41564-023-01505-9
  86. Addetia A, Piccoli L, Case JB, Park YJ, Beltramello M, Guarino B, Dang H, de Melo GD, Pinto D, Sprouse K, et al. Neutralization, effector function and immune imprinting of Omicron variants. Nature 2023;621:592-601.
  87. Hoffmann M, Behrens GM, Arora P, Kempf A, Nehlmeier I, Cossmann A, Manthey L, Dopfer-Jablonka A, Pohlmann S. Effect of hybrid immunity and bivalent booster vaccination on omicron sublineage neutralisation. Lancet Infect Dis 2023;23:25-28. https://doi.org/10.1016/S1473-3099(22)00792-7
  88. Tortorici MA, Addetia A, Seo AJ, Brown J, Sprouse K, Logue J, Clark E, Franko N, Chu H, Veesler D. Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans. Immunity 2024;57:904-911.e4. https://doi.org/10.1016/j.immuni.2024.02.016
  89. Chalkias S, Whatley JL, Eder F, Essink B, Khetan S, Bradley P, Brosz A, McGhee N, Tomassini JE, Chen X, et al. Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results. Nat Med 2023;29:2325-2333. https://doi.org/10.1038/s41591-023-02517-y
  90. Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, McGhee N, Tomassini JE, Chen X, Chang Y, et al. A bivalent omicron-containing booster vaccine against COVID-19. N Engl J Med 2022;387:1279-1291. https://doi.org/10.1056/NEJMoa2208343
  91. World Health Organization. Statement on the antigen composition of COVID-19 vaccines [Internet]. Available at https://www.who.int/news/item/13-12-2023-statement-on-the-antigen-composition-of-covid19-vaccines [accessed on 4 April 2024].
  92. Yisimayi A, Song W, Wang J, Jian F, Yu Y, Chen X, Xu Y, Yang S, Niu X, Xiao T, et al. Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting. Nature 2024;625:148-156. https://doi.org/10.1038/s41586-023-06753-7