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Infection and Immunity, August 2005, p. 4684-4693, Vol. 73, No. 8
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.8.4684-4693.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
T-Cell-Stimulating Protein A Elicits Immune Responses during Meningococcal Carriage and Human Disease
Karen Robinson ,1,
,
Karl G. Wooldridge,1,
Damien B. Wells,1
Amal Hasan,2
Ian Todd,2
Adrian Robins,2
Richard James,1 and
Dlawer A. A. Ala'Aldeen1*
Molecular Bacteriology and Immunology Group, Divisions of Microbiology,1 Immunology, School of Molecular Medical Sciences, University of Nottingham, Queens Medical Centre, Nottingham, NG7 2UH United Kingdom2
Received 23 June 2004/ Returned for modification 1 September 2004/ Accepted 30 March 2005
In recognition of the need for immunological memory-inducing components for future Neisseria meningitidis group B vaccines, we previously searched the proteome of N. meningitidis and identified T-cell-stimulating protein A (TspA). This study was designed to confirm the immunogencity of TspA and to examine the subset of T-helper cell responses to the protein in patients and nasopharyngeal carriers. The tspA gene was reconstructed, cloned, and expressed in Escherichia coli, and the recombinant TspA (rTspA) protein was affinity purified. T-cell proliferative responses to rTspA were detected in the peripheral blood mononuclear cells (PBMCs) of convalescent patients and carriers, confirming that TspA-specific T-cell responses were stimulated by invasive disease and nasopharyngeal colonization. Following stimulation of PBMCs with meningococcal lysate, increased frequencies of both Th1 and Th2 cells were observed, indicating that, as during carriage, invasive meningococcal disease induced an unbiased T-helper subset response. A similar unbiased T-helper response was also detected against rTspA in the PBMCs of convalescent patients. The response of PBMCs from the carriers to TspA stimulation, however, was very weak, and the frequencies of cytokine-positive CD4 cells were not significantly greater than the frequencies in unstimulated control cultures. All of the patients and carriers responded with serum antimeningococcal immunoglobulin G (IgG) antibodies, while four of six samples from patients and 5 of 14 samples from carriers contained detectable anti-rTspA IgG antibodies. Taken together, the results of this study confirmed the immunogenicity of TspA in humans during natural meningococcal infection, and therefore, TspA is worthy of further investigation as a possible T-cell stimulating component of future vaccines.
* Corresponding author. Mailing address: Division of Microbiology & Infectious Diseases, A Floor West Block, University Hospital, Nottingham, NG7 2UH United Kingdom. Phone: 44 (0)115-848-3321. Fax: 44(0)115-970-9233. E-mail: daa{at}nottingham.ac.uk.
Present address: Institute of Infection, Immunity & Inflammation, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH United Kingdom.
K.R. and K.G.W. contributed equally to the present study.
Infection and Immunity, August 2005, p. 4684-4693, Vol. 73, No. 8
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.8.4684-4693.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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