Vaccine 22 (2004) 898–908 Neisseria meningitidis, Neisseria lactamica and Moraxella catarrhalis share cross-reactive carbohydrate antigens Jan M. Braun a,b,∗ , Josef Beuth a , C. Caroline Blackwell c , Sonja Giersen b , Paul G. Higgins d , Georgina Tzanakaki e , Heike Unverhau a , Donald M. Weir f a Institute for Scientific Evaluation of Naturopathy, University of Cologne, Robert Koch Str. 10, 50931 Cologne, Germany b Meningitis-Vaccine, Cologne, Germany c Hunter Immunology Laboratories, Newcastle, NSW, Australia d Institute of Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany e National Meningitis Reference Laboratory, National School of Public Health, Athens, Greece f University of Edinburgh Medical School, Edinburgh, Scotland, UK Abstract Carriage of commensal bacteria species is associated with the development of natural immunity to meningococcal disease, with lipo-oligosaccharides (LOS) of meningococci being one of the main virulence factors associated with severity of meningococcal dis- ease. Meningococcal reference strains and isolates from the commensal species Neisseria lactamica and Moraxella catarrhalis were assessed for the presence of cross-reactive glycoconjugate antigens. Binding of human blood group antibodies of the P and Ii system to meningococcal immunotype reference strains were in accordance with the presence of known LOS carbohydrate structures. Binding studies with meningococcal immunotyping antibodies and blood group phenotyping antibodies to N. lactamica strains from different European countries showed, that a greater number of isolates obtained from native Greek and Scottish adults and children bound anti-meningococcal L(3, 7, 9) immunotyping (P< 0.001), p K (P = 0.035) and paragloboside (P< 0.001) blood group typing antibodies compared to isolates obtained from children of Russian immigrants in Greece. A greater number of M. catarrhalis strains isolated from children in Scotland bound anti-L(3, 7, 9) antibodies (38.2%) compared to strains isolated from adults (22.2%) (P = 0.017). These findings provide evidence that blood group like glycoconjugate antigens found on the commensal species N. lactamica and M. catarrhalis might be involved in the development of natural immunity to meningococcal endotoxins during childhood, and might be exploited as anti-meningococcal vaccine candidates. © 2003 Elsevier Ltd. All rights reserved. Keywords: Meningococcal disease; Endotoxin; Cross-reactivity 1. Introduction Evidence of common oligosaccharide structures for meningococci and Neisseria lactamica (NL) or meningo- cocci and Moraxella catarrhalis (MC) has been reported to share oligosaccharide antigens with some carbohydrate structures found on human tissues including paragloboside, P, P1, p K , and Ii blood group antigens [1]. The expres- sion of blood group related LOS on meningococcal carrier strains and outbreak strains differs greatly. While disease is mainly associated with meningococcal immunotype L(3, 7, 9) showing homology with the paragloboside antigen (a precursor of the human nP1 blood group antigen), carrier strains isolated in Britain were found to express LOS im- munotypes similar to the p K and ceramide-dihexocide blood ∗ Corresponding author. Tel.: +49-170-3030-9853. E-mail address: janmatthias.braun@web.de (J.M. Braun). group antigens L1 and L8, respectively [2]. There has been no systematic screening of commensal NL or MC isolates from different regions of Europe with the immunotype an- tibodies used to classify NM immunotypes or antibodies to human blood group antigens. Thirteen major LOS types were identified for Neisseria meningitidis using polyclonal and monoclonal antibodies by passive haemagglutination inhibition techniques and whole cell ELISA [3,4]. The majority of meningococcal isolates express one or more of the immunotypes L1–L12, while non-typable and L13 immunotypes are rare. The 12 major LOS types have a relative molecular weight ranging from 3.15 to 7.1 kDa. The oligosaccharide chain, also re- ferred to as the -chain or variable LOS region one (R1), is composed of the saccharides glucose (Glc), galactose (Gal), N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc). Sialylated forms contain the terminal saccha- ride N-acetylneuramic acid (NeuNAc) is added to terminal 0264-410X/$ – see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2003.11.036