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A putative amino acid ABC transporter substrate-binding protein, NMB1612, from Neisseria meningitidis, induces murine bactericidal antibodies against meningococci expressing heterologous NMB1612 proteins

A putative amino acid ABC transporter substrate-binding protein, NMB1612, from Neisseria meningitidis, induces murine bactericidal antibodies against meningococci expressing heterologous NMB1612 proteins
A putative amino acid ABC transporter substrate-binding protein, NMB1612, from Neisseria meningitidis, induces murine bactericidal antibodies against meningococci expressing heterologous NMB1612 proteins
The nmb1612 (NEIS1533) gene encoding the ?27-kDa putative amino acid ATP-binding cassette (ABC) transporter, periplasmic substrate-binding protein from Neisseria meningitidis serogroup B (MenB) strain MC58 was cloned and expressed in Escherichia coli, and the purified recombinant (r)NMB1612 was used for animal immunization studies. Immunization of mice with rNMB1612 adsorbed to Al(OH)3 and in liposomes with and without MPLA, induced antiserum with bactericidal activity in an assay using baby rabbit complement, against the homologous strain MC58 (encoding protein representative of Allele 62) and killed heterologous strains encoding proteins of three other alleles (representative of Alleles 1, 64 and 68), with similar SBA titres. However, strain MC58 was not killed (titre <4) in a human serum bactericidal assay (hSBA) using anti-rNMB1612 sera, although another strain (MC168) expressing the same protein was killed (median titres of 16–64 in the hSBA). Analysis of the NMB1612 amino acid sequences from 4351 meningococcal strains in the pubmlst.org/Neisseria database and a collection of 13 isolates from colonized individuals and from patients, showed that antibodies raised against rNMB1612 could potentially kill at least 72% of the MenB strains in the complete sequence database. For MenB disease occurring specifically in the UK from 2013 to 2015, >91% of the isolates causing disease in this recent period expressed NMB1612 protein encoded by Allele 1 and could be potentially killed by sera raised to the recombinant antigen in the current study. The NMB1612 protein was surface-accessible and expressed by different meningococcal strains. In summary, the properties of (i) NMB1612 protein conservation and expression, (ii) limited amino acid sequence variation between proteins encoded by different alleles, and (iii) the ability of a recombinant protein to induce cross-strain bactericidal antibodies, would all suggest a promising antigen for consideration for inclusion in new meningococcal vaccines.
neisseria meningitidis, amino acid ABC transporter, substrate-binding protein, bactericidal activity, meningococcal vaccine, sequence diversity
4486-4494
Hung, Miao-Chiu
46dfe1db-123e-427e-8b58-f7caf50a627e
Humbert, Maria Victoria
49d3bc00-5603-4769-9eab-455a6f47c6cd
Laver, Jay R.
19633c56-03bc-4fb7-9eaa-15f0ada90fa4
Phillips, Renee
0d918224-043e-4492-9a20-8e7e6f632d42
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Hung, Miao-Chiu
46dfe1db-123e-427e-8b58-f7caf50a627e
Humbert, Maria Victoria
49d3bc00-5603-4769-9eab-455a6f47c6cd
Laver, Jay R.
19633c56-03bc-4fb7-9eaa-15f0ada90fa4
Phillips, Renee
0d918224-043e-4492-9a20-8e7e6f632d42
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078

Hung, Miao-Chiu, Humbert, Maria Victoria, Laver, Jay R., Phillips, Renee, Heckels, John E. and Christodoulides, Myron (2015) A putative amino acid ABC transporter substrate-binding protein, NMB1612, from Neisseria meningitidis, induces murine bactericidal antibodies against meningococci expressing heterologous NMB1612 proteins. Vaccine, 33 (36), 4486-4494. (doi:10.1016/j.vaccine.2015.07.032). (PMID:26207592)

Record type: Article

Abstract

The nmb1612 (NEIS1533) gene encoding the ?27-kDa putative amino acid ATP-binding cassette (ABC) transporter, periplasmic substrate-binding protein from Neisseria meningitidis serogroup B (MenB) strain MC58 was cloned and expressed in Escherichia coli, and the purified recombinant (r)NMB1612 was used for animal immunization studies. Immunization of mice with rNMB1612 adsorbed to Al(OH)3 and in liposomes with and without MPLA, induced antiserum with bactericidal activity in an assay using baby rabbit complement, against the homologous strain MC58 (encoding protein representative of Allele 62) and killed heterologous strains encoding proteins of three other alleles (representative of Alleles 1, 64 and 68), with similar SBA titres. However, strain MC58 was not killed (titre <4) in a human serum bactericidal assay (hSBA) using anti-rNMB1612 sera, although another strain (MC168) expressing the same protein was killed (median titres of 16–64 in the hSBA). Analysis of the NMB1612 amino acid sequences from 4351 meningococcal strains in the pubmlst.org/Neisseria database and a collection of 13 isolates from colonized individuals and from patients, showed that antibodies raised against rNMB1612 could potentially kill at least 72% of the MenB strains in the complete sequence database. For MenB disease occurring specifically in the UK from 2013 to 2015, >91% of the isolates causing disease in this recent period expressed NMB1612 protein encoded by Allele 1 and could be potentially killed by sera raised to the recombinant antigen in the current study. The NMB1612 protein was surface-accessible and expressed by different meningococcal strains. In summary, the properties of (i) NMB1612 protein conservation and expression, (ii) limited amino acid sequence variation between proteins encoded by different alleles, and (iii) the ability of a recombinant protein to induce cross-strain bactericidal antibodies, would all suggest a promising antigen for consideration for inclusion in new meningococcal vaccines.

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More information

Accepted/In Press date: 8 July 2015
e-pub ahead of print date: 21 July 2015
Published date: 26 August 2015
Keywords: neisseria meningitidis, amino acid ABC transporter, substrate-binding protein, bactericidal activity, meningococcal vaccine, sequence diversity
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 380759
URI: https://eprints.soton.ac.uk/id/eprint/380759
PURE UUID: 00f61b99-0c87-429b-8411-2fd7e93bb4eb

Catalogue record

Date deposited: 14 Sep 2015 14:03
Last modified: 17 Jul 2017 20:33

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