title: The adhesin complex protein (ACP) of Neisseria meningitidis is a new adhesin with vaccine potential.
abstract: The acp gene encoding the 13-kDa adhesin complex protein (ACP) from Neisseria meningitidis serogroup B strain MC58 was cloned and expressed in Escherichia coli, and the purified recombinant ACP (rACP) was used for immunization studies. Analysis of the ACP amino acid sequences from 13 meningococcal strains, isolated from patients and colonized individuals, and 178 strains in the Bacterial Isolate Genome Sequence (BIGS) database showed the presence of only three distinct sequence types (I, II, and III) with high similarity (> 98%). Immunization of mice with type I rACP in detergent micelles and liposomes and in saline solution alone induced high levels of serum bactericidal activity (SBA; titers of 1/512) against the homologous strain MC58 and killed strains of heterologous sequence types II and III with similar SBA titers (1/128 to 1/512). Levels of expression of type I, II, or III ACP by different meningococcal strains were similar. ACP functioned as an adhesin, as demonstrated by reduced adherence of acp knockout (MC58 ΔACP) meningococci to human cells in vitro and the direct surface binding of rACP and by the ability of anti-rACP sera to inhibit adherence of wild-type bacteria. ACP also mediated the invasion of noncapsular meningococci into human epithelial cells, but it was not a particularly impressive invasin, as the internalized bacterial numbers were low. In summary, the newly identified ACP protein is an adhesin that induces cross-strain bactericidal activity and is therefore an attractive target antigen for incorporation into the next generation of serogroup B meningococcal vaccines.
  
  
  OBJECTIVE
  Infections caused by Neisseria meningitidis serogroup B are still significant causes of mortality and morbidity worldwide, and broadly protective vaccines of defined antigen composition are not yet licensed. Here, we describe the properties of the adhesin complex protein (ACP), which we demonstrate is a newly recognized molecule that is highly conserved and expressed to similar levels in meningococci and facilitates meningococcal interactions with human cells. We also report that a recombinant ACP protein vaccine induces murine antibodies that significantly kill meningococci expressing different ACP. Taken together, these properties demonstrate that ACP merits serious consideration as a component of a broadly protective vaccine against serogroup B meningococci.
authors: Neisseria Research Group, Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors: Miao-Chiu
authors: MC
authors: Hung
authors: John E
authors: JE
authors: Heckels
authors: Myron
authors: M
authors: Christodoulides
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001422:Bacterial Adhesion; D001770:Blood Bactericidal Activity; D002460:Cell Line; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D008970:Molecular Weight; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D022401:Meningococcal Vaccines; D014614:Vaccines, Synthetic