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CVI Accepts, published online ahead of print on 12 March 2008
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CVI.00252-07v1
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Clin. Vaccine Immunol. doi:10.1128/CVI.00252-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Specificity of the sub-capsular antibody responses following serogroup A meningococcal disease in Ethiopian patients

Gunnstein Norheim, Abraham Aseffa, Mohammed Ahmed Yassin, Getahun Mengistu, Afework Kassu, Dereje Fikremariam, Wegene Tamire, Yared Merid, E. Arne Høiby, Dominique A. Caugant, Elisabeth Fritzsønn, Torill Tangen, Berhanu Melak, Degu Berhanu, Morten Harboe, Jan Kolberg, and Einar Rosenqvist*

Division of Infectious Disease Control, Norwegian Institute of Public Health (NIPH), Oslo, Norway; Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia; Liverpool School of Tropical Medicine, Liverpool, UK; Southern Nations, Nationalities and Peoples' Region (SNNPR) Health Bureau, Awassa, Ethiopia; Gondar University Hospital, Gondar, Ethiopia; Department of Internal Medicine, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia; Sidamo Regional Hospital, Yirgalem, Ethiopia; Department of Oral Biology, University of Oslo, Norway, North Gondar Zone Health Bureau, Gondar, Ethiopia; Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

* To whom correspondence should be addressed. Email: einar.rosenqvist{at}fhi.no.


   Abstract

Dissecting the specificities of human antibody responses following serogroup A meningococcal (MenA) disease may be important for the development of improved vaccines. We performed a study in Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients who suffered from meningococcal disease caused by MenA bacteria of sequence type (ST)-7, 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 ELISA for IgG levels against lipooligosaccharide (LOS) L11 and proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM and Opa/OpcA, as well as LOS. Suffering 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 the acute phase levels in late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute phase patient sera as in control sera, while 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.







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