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Clinical and Vaccine Immunology, May 2008, p. 863-871, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00252-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci{triangledown}

Gunnstein Norheim,1 Abraham Aseffa,2 Mohammed Ahmed Yassin,3,4 Getahun Mengistu,5,6 Afework Kassu,5 Dereje Fikremariam,7 Wegene Tamire,7 Yared Merid,4 E. Arne Høiby,1 Dominique A. Caugant,1,8 Elisabeth Fritzsønn,1 Torill Tangen,1 Berhanu Melak,9 Degu Berhanu,2 Morten Harboe,2,10 Jan Kolberg,1 and Einar Rosenqvist1*

Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway,1 Armauer Hansen Research Institute, Addis Ababa, Ethiopia,2 Liverpool School of Tropical Medicine, Liverpool, United Kingdom,3 Southern Nations, Nationalities and Peoples' Region Health Bureau, Awassa, Ethiopia,4 Gondar University Hospital, Gondar, Ethiopia,5 Department of Internal Medicine, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia,6 Sidamo Regional Hospital, Yirgalem, Ethiopia,7 Department of Oral Biology, University of Oslo, Oslo, Norway,8 North Gondar Zone Health Bureau, Gondar, Ethiopia,9 Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway,10

Received 23 June 2007/ Returned for modification 16 August 2007/ Accepted 7 February 2008

Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.


* Corresponding author. Mailing address: Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway. Phone: 47 22 04 26 19. Fax: 47 22 04 25 18. E-mail: einar.rosenqvist{at}fhi.no

{triangledown} Published ahead of print on 12 March 2008.


Clinical and Vaccine Immunology, May 2008, p. 863-871, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00252-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.