본문 바로가기
KERD
논문KCI 등재

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

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

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.

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.

참고문헌 (52)

  1. Dong E, "An interactive web-based dashboard to track COVID-19 in real time", Lancet Infect Dis, 20, pp.533~534 (2020)
  2. Klein NP, "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, 71, pp.352~358 (2022)
  3. Frenck RW Jr, "Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents", N Engl J Med, 385, pp.239~250 (2021)
  4. Baden LR, "Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine", N Engl J Med, 384, pp.403~416 (2021)
  5. Koelle K, "The changing epidemiology of SARS-CoV-2", Science, 375, pp.1116~1121 (2022)
  6. Hui KP, "SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo", Nature, 603, pp.715~720 (2022)
  7. Meng B, "Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity", Nature, 603, pp.706~714 (2022)
  8. Jihye Um, "Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults", Journal of Korean Medical Science, 37(9), pp.1~6 (2022), 대한의학회[DOI]
  9. Garcia-Beltran WF, "mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant", Cell, 185, pp.457~466 (2022)
  10. Hoffmann M, "The Omicron variant is highly resistant against antibody-mediated neutralization : implications for control of the COVID-19 pandemic", Cell, 185, pp.447~456 (2022)
  11. "Press release" (2022)[URL]
  12. "COVID data tracker" (2022)[URL]
  13. Prunas O, "Waning effectiveness of the BNT162b2 vaccine against infection in adolescents in Israel", Clin Infect Dis, 76, pp.113~118 (2023)
  14. Shrotri M, "Spike-antibody waning after second dose of BNT162b2 or ChAdOx1", Lancet, 398, pp.385~387 (2021)
  15. Goldberg Y, "Waning immunity after the BNT162b2 vaccine in Israel", N Engl J Med, 385, pp.e85~ (2021)
  16. Jordan SC, "T cell immune responses to SARS-CoV-2 and variants of concern(Alpha and Delta)in infected and vaccinated individuals", Cell Mol Immunol, 18, pp.2554~2556 (2021)
  17. Sekine T, "Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19", Cell, 183, pp.158~168 (2020)
  18. Tarke A, "Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals", Cell Rep Med, 2, pp.100355~ (2021)
  19. Jung MK, "BNT162b2-induced memory T cells respond to the Omicron variant with preserved polyfunctionality", Nat Microbiol, 7, pp.909~917 (2022)
  20. Jung S, "The generation of stem cell-like memory cells early after BNT162b2 vaccination is associated with durability of memory CD8+ T cell responses", Cell Reports, 40, pp.111138~ (2022)
  21. Muik A, "Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera", Science, 375, pp.678~680 (2022)
  22. GeurtsvanKessel CH, "Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients", Sci Immunol, 7 (2022)
  23. Karron RA, "Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults", JCI Insight, 7, pp.e157963~ (2022)
  24. 나민석, "SARS-CoV-2-Specific T Cell Responses in Patients with COVID-19 and Unexposed Individuals", Immune Network, 21(1), pp.1~11 (2021), 대한면역학회[DOI]
  25. "Elecsys® Anti-SARS-CoV-2 S: Immunoassay for the quantitative determination to the SARS-CoV-2 spike protein"[URL]
  26. "Elecsys® Anti-SARS-CoV-2: Immunoassay for the qualitative detection of antibodies (incl. IgG) against SARS-CoV-2"[URL]
  27. Precopio ML, "Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses", J Exp Med, 204, pp.1405~1416 (2007)
  28. Park SH, "Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus", Gastroenterology, 143, pp.1048~1060 (2012)
  29. Zimmermann P, "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]
  30. Viner RM, "Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults : a systematic review and meta-analysis", JAMA Pediatr, 175, pp.143~156 (2021)
  31. Fleming-Dutra KE, "Association of prior BNT162b2 COVID-19 vaccination with symptomatic SARS-CoV-2 infection in children and adolescents during Omicron predominance", JAMA, 327, pp.2210~2219 (2022)
  32. Accorsi EK, "Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants", JAMA, 327, pp.639~651 (2022)
  33. Burns MD, "Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children", Vaccines(Basel), 10, pp.10~ (2022)
  34. Chen LL, "Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine", Emerg Microbes Infect, 11, pp.543~547 (2022)
  35. Gruell H, "mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant", Nat Med, 28, pp.477~480 (2022)
  36. Lumley SF, "Antibody status and incidence of SARS-CoV-2 infection in health care workers", N Engl J Med, 384, pp.533~540 (2021)
  37. Khoury DS, "Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection", Nat Med, 27, pp.1205~1211 (2021)
  38. Price AM, "BNT162b2 protection against the Omicron variant in children and adolescents", N Engl J Med, 386, pp.1899~1909 (2022)
  39. Peng Q, "Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong", EBioMedicine, 77, pp.103904~ (2022)
  40. Tarke A, "SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron", Cell, 185, pp.847~859 (2022)
  41. Keeton R, "T cell responses to SARS-CoV-2 spike cross-recognize Omicron", Nature, 603, pp.488~492 (2022)
  42. Liu J, "Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron", Nature, 603, pp.493~496 (2022)
  43. Choi SJ, "T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant", Cell Mol Immunol, 19, pp.447~448 (2022)
  44. 박계명, "Omicron Subvariants, Including BA.4 and BA.5, Substantially Preserve T Cell Epitopes of Ancestral SARS-CoV-2", Immune Network, 22(4), pp.1~3 (2022), 대한면역학회[DOI]
  45. Hurme A, "Long-lasting T cell responses in BNT162b2 COVID-19 mRNA vaccinees and COVID-19 convalescent patients", Front Immunol, 13, pp.869990~ (2022)
  46. Oberhardt V, "Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine", Nature, 597, pp.268~273 (2021)
  47. Guerrera G, "BNT162b2 vaccination induces durable SARS-CoV-2-specific T cells with a stem cell memory phenotype", Sci Immunol, 6 (2021)
  48. Rosa Duque JS, "Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents", Nat Commun, 13, pp.3700~ (2022)
  49. McMahan K, "Correlates of protection against SARS-CoV-2 in rhesus macaques", Nature, 590, pp.630~634 (2021)
  50. Zhuang Z, "Mapping and role of T cell response in SARS-CoV-2-infected mice", J Exp Med, 218, pp.e20202187~ (2021)
  51. Bange EM, "CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer", Nat Med, 27, pp.1280~1289 (2021)
  52. Noh JY, "T cell-oriented strategies for controlling the COVID-19 pandemic", Nat Rev Immunol, 21, pp.687~688 (2021)

관련 논문AI추천

Evaluation of Cellular Responses to ChAdOx1-nCoV-19 and BNT162b2 Vaccinations남민정, 문희원, Hur Mina, Kim Hae-Rim, Kim Hanah, Lee Tae Hwan, Seo Jong Do, Yun Yeo-Min대한진단검사의학회 · Annals of Laboratory Medicine2023 · 제43권 제3호SARS-CoV-2-Specific T Cell Responses in Patients with COVID-19 and Unexposed Individuals김아름, 나민석, 신의철대한면역학회 · Immune Network2021 · 제21권 제1호Patients With Mild COVID-19 Exhibit Low Functional Avidity of SARS-CoV-2 Membrane Protein-Reactive CD4+ T Cells고재훈, 고준영, 김아름, 나민석, 박대원, 박수형, 석혜리, 신의철, 정혜원, 최원석, Hee Kyoung Choi, Jae Hyung Jung, Ji Hoon Jeon, Jun Yong Choi, Kyong Ran Peck대한면역학회 · Immune Network2025 · 제25권 제2호Omicron Subvariants, Including BA.4 and BA.5, Substantially Preserve T Cell Epitopes of Ancestral SARS-CoV-2박계명, 신의철, 최성진대한면역학회 · Immune Network2022 · 제22권 제4호Comparison of Antibody and T Cell Responses Induced by Single Doses of ChAdOx1 nCoV-19 and BNT162b2 Vaccines권지수, 김성한, 김지연, 박순주, 박지영, 배성만, 서미현, 이나경, 이현정, 임소윤, 지영미, 차혜희, 허진영, Shum David대한면역학회 · Immune Network2021 · 제21권 제4호Comparison of Four T-cell Assays and Two Binding Antibody Assays in SARS-CoV-2 Vaccinees With or Without Omicron Breakthrough Infection신수, 남민정, 노은연, 송은영, Oh Inseong, Seo Yeon Ju대한진단검사의학회 · Annals of Laboratory Medicine2023 · 제43권 제6호

이 간행물의 다른 논문 (6건)