IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

SARS-CoV-2 mRNA Vaccine Elicits Sustained T Cell Responses Against the Omicron Variant in Adolescents

  • Sujin Choi (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Sang-Hoon Kim (The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS)) ;
  • Mi Seon Han (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yoonsun Yoon (Department of Pediatrics, Korea University Guro Hospital) ;
  • Yun-Kyung Kim (Department of Pediatrics, Korea University College of Medicine) ;
  • Hye-Kyung Cho (Department of Pediatrics, Gil Medical Center, Gachon University College of Medicine) ;
  • Ki Wook Yun (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Seung Ha Song (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Bin Ahn (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Ye Kyung Kim (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Sung Hwan Choi (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Young June Choe (Department of Pediatrics, Korea University Anam Hospital) ;
  • Heeji Lim (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Eun Bee Choi (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Kwangwook Kim (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Seokhwan Hyeon (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Hye Jung Lim (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Byung-chul Kim (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Yoo-kyoung Lee (Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency) ;
  • Eun Hwa Choi (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Eui-Cheol Shin (The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS)) ;
  • Hyunju Lee (Department of Pediatrics, Seoul National University Bundang Hospital)
  • Received : 2023.04.17
  • Accepted : 2023.06.21
  • Published : 2023.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization. However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccine-induced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARS-CoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins. Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein. The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

Keywords

Acknowledgement

This research was funded by the Korea Disease Control and Prevention Agency (No. 2021ER230600) and Institute for Basic Science (IBS), Republic of Korea, under project code IBS-R801-D2.

References

  1. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020;20:533-534.
  2. Klein NP, Stockwell MS, Demarco M, Gaglani M, Kharbanda AB, Irving SA, Rao S, Grannis SJ, Dascomb K, Murthy K, et al. Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA vaccination in preventing COVID-19-associated emergency department and urgent care encounters and hospitalizations among nonimmunocompromised children and adolescents aged 5-17 years - VISION network, 10 states, April 2021-January 2022. MMWR Morb Mortal Wkly Rep 2022;71:352-358.
  3. Frenck RW Jr, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, Perez JL, Walter EB, Senders S, Bailey R, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239-250.
  4. 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.
  5. Koelle K, Martin MA, Antia R, Lopman B, Dean NE. The changing epidemiology of SARS-CoV-2. Science 2022;375:1116-1121.
  6. Hui KP, Ho JC, Cheung MC, Ng KC, Ching RH, Lai KL, Kam TT, Gu H, Sit KY, Hsin MK, et al. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. Nature 2022;603:715-720.
  7. Meng B, Abdullahi A, Ferreira IATM, Goonawardane N, Saito A, Kimura I, Yamasoba D, Gerber PP, Fatihi S, Rathore S, et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature 2022;603:706-714.
  8. Um J, Choi YY, Kim G, Kim MK, Lee KS, Sung HK, Kim BC, Lee YK, Jang HC, Bang JH, et al. Booster BNT162b2 COVID-19 vaccination increases neutralizing antibody titers against the SARS-CoV-2 Omicron variant in both young and elderly adults. J Korean Med Sci 2022;37:e70.
  9. Garcia-Beltran WF, St Denis KJ, Hoelzemer A, Lam EC, Nitido AD, Sheehan ML, Berrios C, Ofoman O, Chang CC, Hauser BM, et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell 2022;185:457-466.e4.
  10. Hoffmann M, Kruger N, Schulz S, Cossmann A, Rocha C, Kempf A, Nehlmeier I, Graichen L, Moldenhauer AS, Winkler MS, et al. The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic. Cell 2022;185:447-456.e11.
  11. Korean Disease Control and Prevention Agency. Press release [Internet]. Available at https://www.kdca.go.kr/board/board.es?mid=a20501000000&bid=0015&list_no=720988&act=view# [updated 2022; accessed on 1 November 2022]. 
  12. Centers for Disease Control and Prevention. COVID data tracker [Internet]. Available at https://covid.cdc. gov/covid-data-tracker [updated 2022; accessed on 1 November 2022]. 
  13. Prunas O, Weinberger DM, Pitzer VE, Gazit S, Patalon T. Waning effectiveness of the BNT162b2 vaccine against infection in adolescents in Israel. Clin Infect Dis 2023;76:113-118.
  14. Shrotri M, Navaratnam AMD, Nguyen V, Byrne T, Geismar C, Fragaszy E, Beale S, Fong WLE, Patel P, Kovar J, et al. Spike-antibody waning after second dose of BNT162b2 or ChAdOx1. Lancet 2021;398:385-387.
  15. Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman L, Haas EJ, Milo R, Alroy-Preis S, Ash N, Huppert A. Waning immunity after the BNT162b2 vaccine in Israel. N Engl J Med 2021;385:e85.
  16. Jordan SC, Shin BH, Gadsden TM, Chu M, Petrosyan A, Le CN, Zabner R, Oft J, Pedraza I, Cheng S, et al. T cell immune responses to SARS-CoV-2 and variants of concern (Alpha and Delta) in infected and vaccinated individuals. Cell Mol Immunol 2021;18:2554-2556.
  17. Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin JB, Olsson A, Llewellyn-Lacey S, Kamal H, Bogdanovic G, Muschiol S, et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 2020;183:158-168.e14.
  18. Tarke A, Sidney J, Methot N, Yu ED, Zhang Y, Dan JM, Goodwin B, Rubiro P, Sutherland A, Wang E, et al. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell Rep Med 2021;2:100355.
  19. Jung MK, Jeong SD, Noh JY, Kim DU, Jung S, Song JY, Jeong HW, Park SH, Shin EC. BNT162b2-induced memory T cells respond to the Omicron variant with preserved polyfunctionality. Nat Microbiol 2022;7:909-917.
  20. Jung S, Jung JH, Noh JY, Kim WJ, Yoon SY, Jung J, Kim ES, Kim HB, Cheong HJ, Kim WJ, et al. The generation of stem cell-like memory cells early after BNT162b2 vaccination is associated with durability of memory CD8+ T cell responses. Cell Reports 2022;40:111138.
  21. Muik A, Lui BG, Wallisch AK, Bacher M, Muhl J, Reinholz J, Ozhelvaci O, Beckmann N, Guimil Garcia RC, Poran A, et al. Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera. Science 2022;375:678-680.
  22. GeurtsvanKessel CH, Geers D, Schmitz KS, Mykytyn AZ, Lamers MM, Bogers S, Scherbeijn S, Gommers L, Sablerolles RS, Nieuwkoop NN, et al. Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients. Sci Immunol 2022;7:eabo2202.
  23. Karron RA, Garcia Quesada M, Schappell EA, Schmidt SD, Deloria Knoll M, Hetrich MK, Veguilla V, Doria-Rose N, Dawood FS; SEARCh Study Team. Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults. JCI Insight 2022;7:e157963.
  24. Rha MS, Kim AR, Shin EC. SARS-CoV-2-specific T cell responses in patients with COVID-19 and unexposed individuals. Immune Netw 2021;21:e2.
  25. Roche Diagnostics International. Elecsys® Anti-SARS-CoV-2 S: Immunoassay for the quantitative determination to the SARS-CoV-2 spike protein [Internet]. Available at https://diagnostics.roche.com/global/en/products/params/elecsys-anti-sars-cov-2-s.html [accessed on August 5, 2022]. 
  26. Roche Diagnostics International. Elecsys® Anti-SARS-CoV-2: Immunoassay for the qualitative detection of antibodies (incl. IgG) against SARS-CoV-2 [Internet]. Available at https://diagnostics.roche.com/global/en/products/params/elecsys-anti-sars-cov-2.html [accessed on August 5, 2022]. 
  27. Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Ambrozak DR, Asher TE, Douek DC, Harari A, Pantaleo G, et al. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses. J Exp Med 2007;204:1405-1416.
  28. Park SH, Shin EC, Capone S, Caggiari L, De Re V, Nicosia A, Folgori A, Rehermann B. Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus. Gastroenterology 2012;143:1048-60.e4.
  29. Zimmermann P, Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child 2020. doi: 10.1136/archdischild-2020-320338.
  30. Viner RM, Mytton OT, Bonell C, Melendez-Torres GJ, Ward J, Hudson L, Waddington C, Thomas J, Russell S, van der Klis F, et al. Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults: a systematic review and meta-analysis. JAMA Pediatr 2021;175:143-156.
  31. Fleming-Dutra KE, Britton A, Shang N, Derado G, Link-Gelles R, Accorsi EK, Smith ZR, Miller J, Verani JR, Schrag SJ. Association of prior BNT162b2 COVID-19 vaccination with symptomatic SARS-CoV-2 infection in children and adolescents during Omicron predominance. JAMA 2022;327:2210-2219.
  32. Accorsi EK, Britton A, Fleming-Dutra KE, Smith ZR, Shang N, Derado G, Miller J, Schrag SJ, Verani JR. Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants. JAMA 2022;327:639-651. 
  33. Burns MD, Boribong BP, Bartsch YC, Loiselle M, St Denis KJ, Sheehan ML, Chen JW, Davis JP, Lima R, Edlow AG, et al. Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children. Vaccines (Basel) 2022;10:10.
  34. Chen LL, Chua GT, Lu L, Chan BP, Wong JS, Chow CC, Yu TC, Leung AS, Lam SY, Wong TW, et al. Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine. Emerg Microbes Infect 2022;11:543-547.
  35. Gruell H, Vanshylla K, Tober-Lau P, Hillus D, Schommers P, Lehmann C, Kurth F, Sander LE, Klein F. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat Med 2022;28:477-480.
  36. Lumley SF, O'Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, Marsden BD, Cox S, James T, Warren F, et al. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med 2021;384:533-540.
  37. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 2021;27:1205-1211.
  38. Price AM, Olson SM, Newhams MM, Halasa NB, Boom JA, Sahni LC, Pannaraj PS, Irby K, Bline KE, Maddux AB, et al. BNT162b2 protection against the Omicron variant in children and adolescents. N Engl J Med 2022;386:1899-1909.
  39. Peng Q, Zhou R, Wang Y, Zhao M, Liu N, Li S, Huang H, Yang D, Au KK, Wang H, et al. Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong. EBioMedicine 2022;77:103904.
  40. Tarke A, Coelho CH, Zhang Z, Dan JM, Yu ED, Methot N, Bloom NI, Goodwin B, Phillips E, Mallal S, et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell 2022;185:847-859.e11.
  41. Keeton R, Tincho MB, Ngomti A, Baguma R, Benede N, Suzuki A, Khan K, Cele S, Bernstein M, Karim F, et al. T cell responses to SARS-CoV-2 spike cross-recognize Omicron. Nature 2022;603:488-492.
  42. Liu J, Chandrashekar A, Sellers D, Barrett J, Jacob-Dolan C, Lifton M, McMahan K, Sciacca M, VanWyk H, Wu C, et al. Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron. Nature 2022;603:493-496.
  43. Choi SJ, Kim DU, Noh JY, Kim S, Park SH, Jeong HW, Shin EC. T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant. Cell Mol Immunol 2022;19:447-448.
  44. Park K, Choi SJ, Shin EC. Omicron subvariants, including BA.4 and BA.5, substantially preserve T cell epitopes of ancestral SARS-CoV-2. Immune Netw 2022;22:e29.
  45. Hurme A, Jalkanen P, Heroum J, Liedes O, Vara S, Melin M, Terasjarvi J, He Q, Poysti S, Hanninen A, et al. Long-lasting T cell responses in BNT162b2 COVID-19 mRNA vaccinees and COVID-19 convalescent patients. Front Immunol 2022;13:869990.
  46. Oberhardt V, Luxenburger H, Kemming J, Schulien I, Ciminski K, Giese S, Csernalabics B, Lang-Meli J, Janowska I, Staniek J, et al. Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine. Nature 2021;597:268-273.
  47. Guerrera G, Picozza M, D'Orso S, Placido R, Pirronello M, Verdiani A, Termine A, Fabrizio C, Giannessi F, Sambucci M, et al. BNT162b2 vaccination induces durable SARS-CoV-2-specific T cells with a stem cell memory phenotype. Sci Immunol 2021;6:eabl5344.
  48. Rosa Duque JS, Wang X, Leung D, Cheng SM, Cohen CA, Mu X, Hachim A, Zhang Y, Chan SM, Chaothai S, et al. Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents. Nat Commun 2022;13:3700.
  49. McMahan K, Yu J, Mercado NB, Loos C, Tostanoski LH, Chandrashekar A, Liu J, Peter L, Atyeo C, Zhu A, et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 2021;590:630-634.
  50. Zhuang Z, Lai X, Sun J, Chen Z, Zhang Z, Dai J, Liu D, Li Y, Li F, Wang Y, et al. Mapping and role of T cell response in SARS-CoV-2-infected mice. J Exp Med 2021;218:e20202187.
  51. Bange EM, Han NA, Wileyto P, Kim JY, Gouma S, Robinson J, Greenplate AR, Hwee MA, Porterfield F, Owoyemi O, et al. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med 2021;27:1280-1289.
  52. Noh JY, Jeong HW, Kim JH, Shin EC. T cell-oriented strategies for controlling the COVID-19 pandemic. Nat Rev Immunol 2021;21:687-688.