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Infection and Immunity, March 2001, p. 1561-1567, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1561-1567.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Recombinant Neisseria meningitidis Transferrin Binding Protein A Protects against Experimental Meningococcal Infection

David West, Karen Reddin, Mary Matheson, Robert Heath, Simon Funnell, Michael Hudson, Andrew Robinson, and Andrew Gorringe*

Centre for Applied Microbiology and Research, Salisbury SP4 0JG, United Kingdom

Received 25 August 2000/Returned for modification 9 October 2000/Accepted 11 December 2000

To better characterize the vaccine potential of Neisseria meningitidis transferrin binding proteins (Tbps), we have overexpressed TbpA and TbpB from Neisseria meningitidis isolate K454 in Escherichia coli. The ability to bind human transferrin was retained by both recombinant proteins, enabling purification by affinity chromotography. The recombinant Tbps were evaluated individually and in combination in a mouse intraperitoneal-infection model to determine their ability to protect against meningococcal infection and to induce cross-reactive and bactericidal antibodies. For the first time, TbpA was found to afford protection against meningococcal challenge when administered as the sole immunogen. In contrast to the protection conferred by TbpB, this protection extended to a serogroup C isolate and strain B16B6, a serogroup B isolate with a lower-molecular-weight TbpB than that from strain K454. However, serum from a TbpB-immunized rabbit was found to be significantly more bactericidal than that from a TbpA-immunized animal. Our evidence demonstrates that TbpA used as a vaccine antigen may provide protection against a wider range of meningococcal strains than does TbpB alone. This protection appears not to be due to complement-mediated lysis and indicates that serum bactericidal activity may not always be the most appropriate predictor of efficacy for protein-based meningococcal vaccines.

* Corresponding author. Mailing address: CAMR, Salisbury SP4 0JG, United Kingdom. Phone: 44 1980 612267. Fax: 44 1980 611310. E-mail: andrew.gorringe{at}camr.org.uk.

Infection and Immunity, March 2001, p. 1561-1567, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1561-1567.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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