• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of cdliPermissionsJournals.ASM.orgAEM ArticleJournal InfoAuthorsReviewers
Clin Diagn Lab Immunol. Mar 1997; 4(2): 156–167.
PMCID: PMC170495

Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group.

Abstract

A standardized serum bactericidal assay (SBA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines. We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SBA titers. The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera. The critical assay parameters for the reproducible measurement of SBA titers were found to include the target strain, assay incubation time, and complement. The resulting standardized SBA was used by 10 laboratories to measure functional anticapsular antibody against serogroup A strains F8238 and serogroup C strain C11. In the multilaboratory study, SBA titers were measured in duplicate for 14 pairs of sera (seven adults and seven children) before and after immunization with a quadrivalent polysaccharide (A, C, Y, and W-135) vaccine. The standardized SBA was reliable in all laboratories regardless of experience in performing SBAs. For most sera, intralaboratory reproducibility was +/- 1 dilution; interlaboratory reproducibility was +/- 2 dilutions. The correlation between median titers (interlaboratory) and enzyme-linked immunosorbent assay total antibody concentrations was high for both serogroup A (r = 0.86; P < 0.001; slope = 0.5) and serogroup C (n = 0.86; P < 0.001; slope = 0.7). The specified assay, which includes the critical parameters of target strain, incubation time, and complement source, will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines.

Full Text

The Full Text of this article is available as a PDF (206K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anderson EL, Bowers T, Mink CM, Kennedy DJ, Belshe RB, Harakeh H, Pais L, Holder P, Carlone GM. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect Immun. 1994 Aug;62(8):3391–3395. [PMC free article] [PubMed]
  • Cadoz M, Armand J, Arminjon F, Gire R, Lafaix C. Tetravalent (A, C, Y, W 135) meningococcal vaccine in children: immunogenicity and safety. Vaccine. 1985 Sep;3(3):340–342. [PubMed]
  • Carlone GM, Frasch CE, Siber GR, Quataert S, Gheesling LL, Turner SH, Plikaytis BD, Helsel LO, DeWitt WE, Bibb WF, et al. Multicenter comparison of levels of antibody to the Neisseria meningitidis group A capsular polysaccharide measured by using an enzyme-linked immunosorbent assay. J Clin Microbiol. 1992 Jan;30(1):154–159. [PMC free article] [PubMed]
  • Craven DE, Shen KT, Frasch CE. Natural bactericidal activity of human serum against Neisseria meningitidis isolates of different serogroups and serotypes. Infect Immun. 1982 Jul;37(1):132–137. [PMC free article] [PubMed]
  • DAVIS SD, WEDGWOOD RJ. KINETICS OF THE BACTERICIDAL ACTION OF NORMAL SERUM ON GRAM-NEGATIVE BACTERIA. J Immunol. 1965 Jul;95:75–79. [PubMed]
  • Frasch CE, Robbins JD. Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model. J Exp Med. 1978 Mar 1;147(3):629–644. [PMC free article] [PubMed]
  • Gheesling LL, Carlone GM, Pais LB, Holder PF, Maslanka SE, Plikaytis BD, Achtman M, Densen P, Frasch CE, Käyhty H, et al. Multicenter comparison of Neisseria meningitidis serogroup C anti-capsular polysaccharide antibody levels measured by a standardized enzyme-linked immunosorbent assay. J Clin Microbiol. 1994 Jun;32(6):1475–1482. [PMC free article] [PubMed]
  • Gold R, Wyle FA. New Classification of Neisseria meningitidis by Means of Bactericidal Reactions. Infect Immun. 1970 May;1(5):479–484. [PMC free article] [PubMed]
  • Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969 Jun 1;129(6):1307–1326. [PMC free article] [PubMed]
  • Gotschlich EC, Goldschneider I, Artenstein MS. Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers. J Exp Med. 1969 Jun 1;129(6):1367–1384. [PMC free article] [PubMed]
  • Gotschlich EC, Liu TY, Artenstein MS. Human immunity to the meningococcus. 3. Preparation and immunochemical properties of the group A, group B, and group C meningococcal polysaccharides. J Exp Med. 1969 Jun 1;129(6):1349–1365. [PMC free article] [PubMed]
  • Griffiss JM, Goroff DK. IgA blocks IgM and IgG-initiated immune lysis by separate molecular mechanisms. J Immunol. 1983 Jun;130(6):2882–2885. [PubMed]
  • Holder PK, Maslanka SE, Pais LB, Dykes J, Plikaytis BD, Carlone GM. Assignment of Neisseria meningitidis serogroup A and C class-specific anticapsular antibody concentrations to the new standard reference serum CDC1992. Clin Diagn Lab Immunol. 1995 Mar;2(2):132–137. [PMC free article] [PubMed]
  • Kasper DL, Winkelhake JL, Brandt BL, Artenstein MS. Antigenic specificity of bactericidal antibodies in antisera to Neisseria meningitidis. J Infect Dis. 1973 Apr;127(4):378–387. [PubMed]
  • King WJ, MacDonald NE, Wells G, Huang J, Allen U, Chan F, Ferris W, Diaz-Mitoma F, Ashton F. Total and functional antibody response to a quadrivalent meningococcal polysaccharide vaccine among children. J Pediatr. 1996 Feb;128(2):196–202. [PubMed]
  • Leach A, Twumasi PA, Kumah S, Banya WS, Jaffar S, Forrest BD, Granoff DM, LiButti DE, Carlone GM, Pais LB, et al. Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine. J Infect Dis. 1997 Jan;175(1):200–204. [PubMed]
  • Mandrell RE, Azmi FH, Granoff DM. Complement-mediated bactericidal activity of human antibodies to poly alpha 2-->8 N-acetylneuraminic acid, the capsular polysaccharide of Neisseria meningitidis serogroup B. J Infect Dis. 1995 Nov;172(5):1279–1289. [PubMed]
  • Milagres LG, Ramos SR, Sacchi CT, Melles CE, Vieira VS, Sato H, Brito GS, Moraes JC, Frasch CE. Immune response of Brazilian children to a Neisseria meningitidis serogroup B outer membrane protein vaccine: comparison with efficacy. Infect Immun. 1994 Oct;62(10):4419–4424. [PMC free article] [PubMed]
  • Mitchell LA, Ochnio JJ, Glover C, Lee AY, Ho MK, Bell A. Analysis of meningococcal serogroup C-specific antibody levels in British Columbian children and adolescents. J Infect Dis. 1996 Apr;173(4):1009–1013. [PubMed]
  • Moran EE, Brandt BL, Zollinger WD. Expression of the L8 lipopolysaccharide determinant increases the sensitivity of Neisseria meningitidis to serum bactericidal activity. Infect Immun. 1994 Dec;62(12):5290–5295. [PMC free article] [PubMed]
  • Nicholson A, Lepow IH. Host defense against Neisseria meningitidis requires a complement-dependent bactericidal activity. Science. 1979 Jul 20;205(4403):298–299. [PubMed]
  • Peltola H, Mäkelä H, Käyhty H, Jousimies H, Herva E, Hällström K, Sivonen A, Renkonen OV, Pettay O, Karanko V, et al. Clinical efficacy of meningococcus group A capsular polysaccharide vaccine in children three months to five years of age. N Engl J Med. 1977 Sep 29;297(13):686–691. [PubMed]
  • Plikaytis BD, Holder PF, Pais LB, Maslanka SE, Gheesling LL, Carlone GM. Determination of parallelism and nonparallelism in bioassay dilution curves. J Clin Microbiol. 1994 Oct;32(10):2441–2447. [PMC free article] [PubMed]
  • Reingold AL, Broome CV, Hightower AW, Ajello GW, Bolan GA, Adamsbaum C, Jones EE, Phillips C, Tiendrebeogo H, Yada A. Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine. Lancet. 1985 Jul 20;2(8447):114–118. [PubMed]
  • Ross SC, Berberich HM, Densen P. Natural serum bactericidal activity against Neisseria meningitidis isolates from disseminated infections in normal and complement-deficient hosts. J Infect Dis. 1985 Dec;152(6):1332–1335. [PubMed]
  • Söderström C, Braconier JH, Danielsson D, Sjöholm AG. Bactericidal activity for Neisseria meningitidis in properdin-deficient sera. J Infect Dis. 1987 Jul;156(1):107–112. [PubMed]
  • Thomas L, Dingle JH. INVESTIGATIONS OF MENINGOCOCCAL INFECTION. III. THE BACTERICIDAL ACTION OF NORMAL AND IMMUNE SERA FOR THE MENINGOCOCCUS. J Clin Invest. 1943 May;22(3):375–385. [PMC free article] [PubMed]
  • Wedege E, Høiby EA, Rosenqvist E, Frøholm LO. Serotyping and subtyping of Neisseria meningitidis isolates by co-agglutination, dot-blotting and ELISA. J Med Microbiol. 1990 Mar;31(3):195–201. [PubMed]
  • Weibel RE, Villarejos VM, Vella PP, Woodhour AF, Mclean AA, Hilleman MR. Clinical and laboratory investigations of monovalent and combined meningococcal polysaccharide vaccine, groups A and C. Proc Soc Exp Biol Med. 1976 Dec;153(3):436–440. [PubMed]
  • Wong KH, Barrera O, Sutton A, May J, Hochstein DH, Robbins JD, Robbins JB, Parkman PD, Seligmann EB., Jr Standardization and control of meningococcal vaccines, group A and group C polysaccharides. J Biol Stand. 1977;5(3):197–215. [PubMed]
  • Zangwill KM, Stout RW, Carlone GM, Pais L, Harekeh H, Mitchell S, Wolfe WH, Blackwood V, Plikaytis BD, Wenger JD. Duration of antibody response after meningococcal polysaccharide vaccination in US Air Force personnel. J Infect Dis. 1994 Apr;169(4):847–852. [PubMed]
  • Zollinger WD, Boslego J, Frøholm LO, Ray JS, Moran EE, Brandt BL. Human bactericidal antibody response to meningococcal outer membrane protein vaccines. Antonie Van Leeuwenhoek. 1987;53(6):403–411. [PubMed]
  • Zollinger WD, Mandrell RE. Importance of complement source in bactericidal activity of human antibody and murine monoclonal antibody to meningococcal group B polysaccharide. Infect Immun. 1983 Apr;40(1):257–264. [PMC free article] [PubMed]

Articles from Clinical and Diagnostic Laboratory Immunology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...