title: Relationships between functional assays and enzyme immunoassays as measurements of responses to acellular and whole-cell pertussis vaccines.
abstract: OBJECTIVE
  To examine the relationships between functional assays and antigen-specific enzyme immunoassays in sera from a multicenter trial of 13 different experimental acellular pertussis vaccines and 2 licensed whole-cell vaccines, and to determine whether correlations previously observed among assays of specimens from pertussis patients and whole-cell vaccinees would apply to specimens from infants immunized with purified components in acellular vaccines.
  
  
  METHODS
  Postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin (PT), filamentous hemagglutinin, pertactin (PRN), and a mixture of types 2 and 3 fimbriae (FIM) by enzyme-linked immunosorbent assay, for whole-cell agglutinins (AGGs) and for PT-neutralizing antibodies by the Chinese hamster ovary (CHO) cell assay. Assay results were compared for individual sera, as well as for geometric mean antibody concentrations or titers (GMTs) calculated by vaccine or overall.
  
  
  RESULTS
  For the 15 vaccines, the PT GMTs were highly correlated with the CHO assay GMTs (r = .92), and the FIM GMTs were highly correlated with the AGG GMTs (r = .96). For individual postvaccination sera, there was a significant correlation between the CHO titers and levels of antibody to PT whether the 15 vaccines were considered separately (.59 < or = r < or = .85) or combined (r = .81). For individual sera from infants immunized with the two whole-cell vaccines or any of the four acellular vaccines containing FIM, a strong correlation between AGG titer and FIM antibody was observed whether the vaccines were considered separately (.83 < or = r < or = .91) or together (r = .86). One vaccine without detectable FIM produced a measurable AGG response; for this vaccine, a moderate but significant correlation (R = .58) between PRN antibody and AGG titer was observed.
  
  
  CONCLUSIONS
  These data indicate that appropriate antigen-specific enzyme-linked immunosorbent assays will furnish results similar to those provided by the CHO and AGG assays in the evaluation of the immunogenicity of component vaccines. Antibodies to FIM seem to include the most important AGGs; however, there is evidence that agglutination by PRN antibody may be detected in the absence of antibody to FIM.
authors.affiliation: Division of Bacterial Products, Food and Drug Administration, Rockville, MD 20852-1448, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Meade
authors.forename: F
authors.initials: F
authors.lastname: Lynn
authors.forename: G F
authors.initials: GF
authors.lastname: Reed
authors.forename: C M
authors.initials: CM
authors.lastname: Mink
authors.forename: T A
authors.initials: TA
authors.lastname: Romani
authors.forename: A
authors.initials: A
authors.lastname: Deforest
authors.forename: M A
authors.initials: MA
authors.lastname: Deloria
mesh_terms: D000372:Agglutination Tests; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001886:Bordetella pertussis / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D010861:Fimbriae, Bacterial / Q000276:immunology; D006801:Humans; D007159:Immunologic Tests; D007223:Infant; D010567:Pertussis Vaccine / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D010567:Pertussis Vaccine