한국 12-23개월 소아에서 7가 폐구균 단백결합 백신 추가접종으로 유도된 6B와 19F 혈청형 특이 방어항체의 교차혈청형 6A, 6C, 19A에 대한 교차 반응
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
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
목 적 : 폐구균 단백결합 백신의 교차혈청형에 대한 교차방어 능력에 대한 연구는 매우 부족하다. 본 연구는12-23개월 연령 소아에게 PCV7 추가접종 후 얻어진면역혈청에서 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 ELISA 와 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 면역혈청의6B와 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, 19F 를 포함한 PCV7은 교차혈청형 6A,6C, 19A에 대한 IgG 및 IgM 교차방어 항체를 유도하였다. IgM 방어항체는 IgG 항체와 비교하여 백신 혈청형뿐아니라 백신-연관 혈청형에 대해 더 높은 옵소닌 인덱스를 나타내었다. 향후 더 많은 소아와 성인의 면역 혈청으로 연구가 필요하다.
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 vaccinerelated 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.
참고문헌 (33)
- The Korean Pediatric Society, "Pneumococcal vaccine. In: Lee HJ, editor. Immunization Guideline", pp.160~174 (2012), The Korean Pediatric Society
- Lagergard T, "Nature of cross-reactivity between Haemophilus influenzae types A and B and Streptococcus pneumoniae types 6A and 6B", Acta Pathol Microbiol Immunol Scand, 91, pp.371~376 (1983)
- Jakobsen H, "Pneumococcal serotype 19F conjugate vaccine induces cross-protective immunity to serotype 19A in a murine pneumococcal pneumonia model", Infect Immun, 71, pp.2956~2959 (2003)
- Lee CJ, "Protective immunity of pneumococcal glycoconjugates", Crit Rev Microbiol, 29, pp.333~349 (2003)
- Saeland E, "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, 183, pp.253~260 (2001)
- Richter SS, "Changing epidemiology of antimicrobialresistant Streptococcus pneumoniae in the United States, 2004-2005", Clin Infect Dis, 48, pp.e23~e33 (2009)
- Cohen R., "The need for prudent use of antibiotics and routine use of vaccines", Clin Microbiol Infect, 15(Suppl 3), pp.S21~S23 (2009)
- 최은화, "Recommendation for use of the newly introduced pneumococcal protein conjugate vaccines in Korea", Korean Journal of Pediatrics, 54(4), pp.146~151 (2011), 대한소아과학회
- 김경효, "Nasopharyngeal Pneumococcal Carriage of Children Attending Day Care Centers in Korea: Comparison between Children Immunized with 7-valent Pneumococcal Conjugate Vaccine and Non-immunized", Journal of Korean Medical Science, 26(2), pp.184~190 (2011), 대한의학회
- Pelton SI, "Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine", Pediatr Infect Dis J, 26, pp.468~472 (2007)
- Park IH, "Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae", J Clin Microbiol, 45, pp.1225~1233 (2007)
- Park IH, "Differential effects of pneumococcal vaccines against serotypes 6A and 6C", J Infect Dis, 198, pp.1818~1822 (2008)
- Lee H, "Immune response in infants to the heptavalent pneumococcal conjugate vaccine against vaccine-related serotypes 6A and 19A", Clin Vaccine Immunol, 16, pp.376~381 (2009)
- Bryant KA, "Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine", Pediatrics, 125, pp.866~875 (2010)
- Nuorti JP, "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, 59, pp.1~18 (2010)
- 이현주, "Immune response to 19A serotype after immunization of 19F containing pneumococcal conjugate vaccine in Korean children aged 12-23 months", Korean Journal of Pediatrics, 54(4), pp.163~168 (2011), 대한소아과학회
- Cha JH, "Immune responses against serogroup 6 (6A, 6B, 6C, and 6D) among subjects vaccinated with the 7-valent pneumococcal conjugate vaccine", 박사, School of Medicine, pp.2012
- Simell B, "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, 19, pp.1618~1623 (2012)
- Burton RL, "Development and validation of a fourfold multiplexed opsonization assay (MOPA4) for pneumococcal antibodies", Clin Vaccine Immunol, 13, pp.1004~1009 (2006)
- Mond JJ, "T cell-independent antigens type 2", Annu Rev Immunol, 13, pp.655~692 (1995)
- de Vinuesa CG, "Germinal centers without T cells", J Exp Med, 191, pp.485~494 (2000)
- Lentz VM, "Cutting edge: germinal centers can be induced in the absence of T cells", J Immunol, 167, pp.15~20 (2001)
- Toellner KM, "Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers", J Exp Med, 195, pp.383~389 (2002)
- Obukhanych TV, "T-independent type II immune responses generate memory B cells", J Exp Med, 203, pp.305~310 (2006)
- Shi Y, "Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell", J Immunol, 175, pp.3262~3267 (2005)
- Maxwell KF, "Crystal structure of the human leukocyte Fc receptor, FcγRIIa", Nat Struct Biol, 6, pp.437~442 (1999)
- Yee AM, "Association between FcγRIIa-R131 allotype and bacteremic pneumococcal pneumonia", Clin Infect Dis, 30, pp.25~28 (2000)
- Yuan FF, "FcγRIIA polymorphisms in Streptococcus pneumoniae infection", Immunol Cell Biol, 81, pp.192~195 (2003)
- Stray-Pedersen A, "Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia", Clin Exp Immunol, 140, pp.507~516 (2005)
- Mackenzie GA, "Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination", BMC pediatr, 9, pp.14~ (2009)
- Baxendale HE, "Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease", Clin Exp Immunol, 151, pp.51~60 (2008)
- Raff HV, "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, 163, pp.346~354 (1991)
- Shyur SD, "Comparison of the opsonic and complement triggering activity of human monoclonal IgG1 and IgM antibody against group B streptococci", J Immunol, 148, pp.1879~1884 (1992)