The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> 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 mening...

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Autores principales:	Miao-Chiu Hung, John E. Heckels, Myron Christodoulides
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/700ed2bdae044601b4e72b7c83e752e2
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spelling	oai:doaj.org-article:700ed2bdae044601b4e72b7c83e752e22021-11-15T15:40:26ZThe Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential10.1128/mBio.00041-132150-7511https://doaj.org/article/700ed2bdae044601b4e72b7c83e752e22013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00041-13https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE 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.Miao-Chiu HungJohn E. HeckelsMyron ChristodoulidesAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Miao-Chiu Hung John E. Heckels Myron Christodoulides The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential
description	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. IMPORTANCE 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.
format	article
author	Miao-Chiu Hung John E. Heckels Myron Christodoulides
author_facet	Miao-Chiu Hung John E. Heckels Myron Christodoulides
author_sort	Miao-Chiu Hung
title	The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential
title_short	The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential
title_full	The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential
title_fullStr	The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential
title_full_unstemmed	The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential
title_sort	adhesin complex protein (acp) of <named-content content-type="genus-species">neisseria meningitidis</named-content> is a new adhesin with vaccine potential
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/700ed2bdae044601b4e72b7c83e752e2
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The Adhesin Complex Protein (ACP) of <named-content content-type="genus-species">Neisseria meningitidis</named-content> Is a New Adhesin with Vaccine Potential

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