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Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design

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Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design. / Andreae, Clio; Sessions, Richard; Virji, Mumtaz; Hill, Darryl.

In: PLoS ONE, Vol. 13, No. 3, 193940, 16.03.2018.

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@article{383335aa44a8487ba43835bc2c9b8818,
title = "Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design",
abstract = "Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.",
author = "Clio Andreae and Richard Sessions and Mumtaz Virji and Darryl Hill",
year = "2018",
month = "3",
day = "16",
doi = "10.1371/journal.pone.0193940",
language = "English",
volume = "13",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

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TY - JOUR

T1 - Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design

AU - Andreae, Clio

AU - Sessions, Richard

AU - Virji, Mumtaz

AU - Hill, Darryl

PY - 2018/3/16

Y1 - 2018/3/16

N2 - Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.

AB - Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.

UR - http://www.scopus.com/inward/record.url?scp=85044158385&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0193940

DO - 10.1371/journal.pone.0193940

M3 - Article

VL - 13

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - 193940

ER -