Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
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Cross-reaction of 6B and 19F Specific Antibodies to Serotypes 6A, 6C, and 19A after Immunization with 7-valent Pneumococcal Conjugate Vaccine in Korean Children Aged 12-23 Months

한국 12-23개월 소아에서 7가 폐구균 단백결합 백신 추가접종으로 유도된 6B와 19F 혈청형 특이 방어항체의 교차혈청형 6A, 6C, 19A에 대한 교차 반응

  • Kim, Kyung-Hyo (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Yang, Joo Yun (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Park, In Ho (Center for Vaccine Evaluation and Study, School of Medicine, Ewha Womans University) ;
  • Lim, Soo Young (Center for Vaccine Evaluation and Study, School of Medicine, Ewha Womans University)
  • 김경효 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 양주연 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 박인호 (이화여자대학교 의과학연구소 백신효능연구센터) ;
  • 임수영 (이화여자대학교 의과학연구소 백신효능연구센터)
  • Received : 2013.01.18
  • Accepted : 2013.04.03
  • Published : 2013.08.25
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Abstract

Purpose: The cross-protection of 7-valent pneumococcal conjugate vaccine (PCV7) against vaccine-related serotypes has been controversial. We investigated the serological properties of cross-protective antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in young children aged 12-23 months after booster immunization of PCV7. Methods: IgG and IgM antibody concentrations and opsonic index (OI) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were measured by ELISA and opsonophagocytic killing assay (OPA) in 4 selected immunesera. The serological properties and antigenic specificity of protective antibodies were determined by IgM depletion of immunesera, OPA, and competitive OPA against serogroup 6 and 19 pneumococci. Results: Compared to pre-IgM depleted immunesera, OI of IgM-depleted immunesera against 6B and 19F decreased and OI against 6A, 6C, and 19A decreased, too. In competition OPA, free 6B and 19F polysaccharide completely inhibited the immune protection against vaccine-related serotypes 6A, 6C, and 19A as well as vaccine types 6B and 19F. Conclusions: The booster immunization of PCV7 certainly induced cross-protective antibodies against vaccine-related serotypes 6A, 6C, and 19A with both IgG and IgM isotypes. Furthermore, IgM antibodies are more highly contributed to opsonophagocytic activity against vaccine-related serotypes as well as most of vaccine types than do IgG antibodies. Further studies are needed for the more immunized sera in the children as well as adults.

목 적 : 폐구균 단백결합 백신의 교차혈청형에 대한 교차방어 능력에 대한 연구는 매우 부족하다. 본 연구는 12-23개월 연령 소아에게 PCV7 추가접종 후 얻어진 면역혈청에서 교차혈청형 6A, 6C, 19A에 대한 교차 항체의 혈청학적 특성을 연구하기 위해 수행하였다. 방 법 : 백신 혈청형 6B, 19F와 교차혈청형 6A, 6C, 19A의 IgG, IgM 항체 농도와 옵소닌 인덱스를 ELISA와 OPA를 통해 측정하였다. 혈청군 6과 19에 대한 방어항체의 혈청학적 특성과 항원 특이도는 면역혈청내 IgM 제거, OPA, cOPA를 통해 확인하였다. 결 과 : 대조군 혈청에 비교하여 IgM 제거 면역혈청의 6B와 19F에 대한 옵소닌 인덱스가 감소하였고, 6A, 6C, 19A에 대한 옵소닌 인덱스도 역시 감소하였다. cOPA에서 6B 다당질, 19F다당질은 백신 혈청형 6B, 19F 뿐 아니라 6A, 6C, 19A의 방어 면역도 완전히 억제하였다. 결 론 : 6B, 19F를 포함한 PCV7은 교차혈청형 6A, 6C, 19A에 대한 IgG 및 IgM 교차방어 항체를 유도하였다. IgM 방어항체는 IgG 항체와 비교하여 백신 혈청형뿐 아니라 백신-연관 혈청형에 대해 더 높은 옵소닌 인덱스를 나타내었다. 향후 더 많은 소아와 성인의 면역 혈청으로 연구가 필요하다.

Keywords

References

  1. The Korean Pediatric Society. Pneumococcal vaccine. In: Lee HJ, editor. Immunization Guideline. 7th ed. Seoul: The Korean Pediatric Society; 2012. pp. 160-74.
  2. Lagergard T and Branefors P. Nature of cross-reactivity between Haemophilus influenzae types A and B and Streptococcus pneumoniae types 6A and 6B. Acta Pathol Microbiol Immunol Scand 1983;91:371-6.
  3. Jakobsen H, Sigurdsson VD, Sigurdardottir S, Schulz D, Jonsdottir I. Pneumococcal serotype 19F conjugate vaccine induces cross-protective immunity to serotype 19A in a murine pneumococcal pneumonia model. Infect Immun 2003;71:2956-9. https://doi.org/10.1128/IAI.71.5.2956-2959.2003
  4. Lee CJ, Lee LH, Frasch CE. Protective immunity of pneumococcal glycoconjugates. Crit Rev Microbiol 2003;29:333-49. https://doi.org/10.1080/713608018
  5. Saeland E, Jakobsen H, Ingolfsdottir G, Sigurdardottir ST, Jonsdottir I. Serum samples from infants vaccinated with a pneumococcal conjugate vaccine, PncT, protect mice against invasive infection caused by Streptococcus pneumoniae serotypes 6A and 6B. J Infect Dis 2001;183:253-60. https://doi.org/10.1086/317934
  6. Richter SS, Heilmann KP, Dohrn CL, Riahi F, Beekmann SE, Doern GV. Changing epidemiology of antimicrobialresistant Streptococcus pneumoniae in the United States, 2004-2005. Clin Infect Dis 2009;48:e23-33. https://doi.org/10.1086/595857
  7. Cohen R. The need for prudent use of antibiotics and routine use of vaccines. Clin Microbiol Infect 2009;15(Suppl 3):S21-3.
  8. Choi EH, Kim KH, Kim YJ, Kim JH, Park SE, Lee HJ, et al. Recommendation for use of the newly introduced pneumococcal protein conjugate vaccines in Korea. Korean J Pediatr 2011;54:146-51. https://doi.org/10.3345/kjp.2011.54.4.146
  9. Kim KH, Hong JY, Lee H, Kwak GY, Nam CH, Lee YS, et al. Nasopharyngeal pneumococcal carriage of children attending day care centers in Korea: comparison between children immunized with 7-valent pneumococcal conjugate vaccine and non-immunized. J Korean Med Sci 2011;26:184-90. https://doi.org/10.3346/jkms.2011.26.2.184
  10. Pelton SI, Huot H, Finkelstein JA, Bishop CJ, Hsu KK, Kellenber J, et al. Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal coccal conjugate vaccine. Pediatr Infect Dis J 2007;26:468-72. https://doi.org/10.1097/INF.0b013e31803df9ca
  11. Park IH, Pritchard DG, Cartee R, Brandao A, Brandileone MC, Nahm MH. Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae. J Clin Microbiol 2007;45:1225-33. https://doi.org/10.1128/JCM.02199-06
  12. Park IH, Moore MR, Treanor JJ, Pelton SI, Pilishvili T, Beall B, et al. Differential effects of pneumococcal vaccines against serotypes 6A and 6C. J Infect Dis 2008;198:1818-22. https://doi.org/10.1086/593339
  13. Lee H, Nahm MH, Burton R, Kim KH. Immune response in infants to the heptavalent pneumococcal conjugate vaccine against vaccine-related serotypes 6A and 19A. Clin Vaccine Immunol 2009;16:376-81. https://doi.org/10.1128/CVI.00344-08
  14. Bryant KA, Block SL, Baker SA, Gruber WC, Scott DA. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine. Pediatrics 2010;125:866-75. https://doi.org/10.1542/peds.2009-1405
  15. Nuorti JP and Whitney CG. Prevention of pneumococcal disease among infants and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010;59:1-18.
  16. Lee HJ, Park SE, Kim KH. Immune response to 19A serotype after immunization of 19F containing pneumococcal conjugate vaccine in Korean children aged 12-23 months. Korean J Pediatr 2011;54:163-8. https://doi.org/10.3345/kjp.2011.54.4.163
  17. Cha JH. Immune responses against serogroup 6 (6A, 6B, 6C, and 6D) among subjects vaccinated with the 7-valent pneumococcal conjugate vaccine. Ph.D. dissertation, School of Medicine, Ewha Womans University, Seoul 2012
  18. Simell B, Nurkka A, Ekstrom N, Givon-Lavi N, Kayhty H, Dagan R. Serum IgM antibodies contribute to high levels of opsonophagocytic activities in toddlers immunized with a single dose of the 9-valent pneumococcal conjugate vaccine. Clin Vaccine Immunol 2012;19:1618-23. https://doi.org/10.1128/CVI.00248-12
  19. Burton RL and Nahm MH. Development and validation of a fourfold multiplexed opsonization assay (MOPA4) for pneumococcal antibodies. Clin Vaccine Immunol 2006;13:1004-9. https://doi.org/10.1128/CVI.00112-06
  20. Mond JJ, Lees A, Snapper CM. T cell-independent antigens type 2. Annu Rev Immunol 1995;13:655-92. https://doi.org/10.1146/annurev.iy.13.040195.003255
  21. de Vinuesa CG, Cook MC, Ball J, Sunners Y, Cascalho M, Wabl M, et al. Germinal centers without T cells. J Exp Med 2000;191:485-94. https://doi.org/10.1084/jem.191.3.485
  22. Lentz VM and Manser T. Cutting edge: germinal centers can be induced in the absence of T cells. J Immunol 2001;167:15-20. https://doi.org/10.4049/jimmunol.167.1.15
  23. Toellner KM, Jenkinson WE, Taylor DR, Khan M, Sze DMY, Sansom DM, et al. Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers. J Exp Med 2002;195:383-9. https://doi.org/10.1084/jem.20011112
  24. Obukhanych TV and Nussenzweig MC. T-independent type II immune responses generate memory B cells. J Exp Med 2006;203:305-10. https://doi.org/10.1084/jem.20052036
  25. Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol 2005;175:3262-7. https://doi.org/10.4049/jimmunol.175.5.3262
  26. Maxwell KF, Powell MS, Hulett MD, Barton PA, Mc- Kenzie IFC, Garrett TPJ, et al. Crystal structure of the human leukocyte Fc receptor, Fc$\gamma$RIIa. Nat Struct Biol 1999;6:437-42. https://doi.org/10.1038/8241
  27. Yee AM, Phan HM, Zuniga R, Salmon JE, Musher DM. Association between Fc$\gamma$RIIa-R131 allotype and bacteremic pneumococcal pneumonia. Clin Infect Dis 2000;30:25-8. https://doi.org/10.1086/313588
  28. Yuan FF, Wong M, Pererva N, Keating J, Davis AR, Bryant JA, et al. Fc$\gamma$RIIA polymorphisms in Streptococcus pneumoniae infection. Immunol Cell Biol 2003;81:192-5. https://doi.org/10.1046/j.1440-1711.2003.01158.x
  29. Stray-Pedersen A, Aaberge IS, Fruh A, Abrahamsen TG. Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia. Clin Exp Immunol 2005;140:507-16. https://doi.org/10.1111/j.1365-2249.2005.02791.x
  30. Mackenzie GA, Carapetis JR, Leach AJ, Morris PS. Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination. BMC pediatr 2009;9:14. https://doi.org/10.1186/1471-2431-9-14
  31. Baxendale HE, Johnson M, Stephens RC, Yuste J, Klein N, Brown JS, et al. Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease. Clin Exp Immunol 2008;151:51-60.
  32. Raff HV, Bradley C, Brady W, Donaldson K, Lipsich L, Maloney G, et al. Comparison of functional activities between IgG1 and IgM class-switched human monoclonal antibodies reactive with group B streptococci or Escherichia coli K1. J Infect Dis 1991;163:346-54. https://doi.org/10.1093/infdis/163.2.346
  33. Shyur SD, Raff HV, Bohnsack JF, Kelsey DK, Hill HR. Comparison of the opsonic and complement triggering activity of human monoclonal IgG1 and IgM antibody against group B streptococci. J Immunol 1992;148:1879-84.