Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 8; pp. 3770 - 3775
• Main Authors: Serruto, Davide, Spadafina, Tiziana, Ciucchi, Laura, Lewis, Lisa A, Ram, Sanjay, Tontini, Marta, Santini, Laura, Biolchi, Alessia, Seib, Kate L, Giuliani, Marzia M, Donnelly, John J, Berti, Francesco, Savino, Silvana, Scarselli, Maria, Costantino, Paolo, Kroll, J. Simon, O'Dwyer, Clíona, Qiu, Jiazhou, Plaut, Andrew G, Moxon, Richard, Rappuoli, Rino, Pizza, Mariagrazia, Aricò, Beatrice
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23-02-2010; National Acad Sciences
• Subjects: Amino Acid Sequence; Animal models; Antibodies; Antibodies, Bacterial - blood; Antigens; Antigens, Bacterial - chemistry; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - immunology; Bacteria; Binding sites; Biological Sciences; Blood Proteins - chemistry; Blood Proteins - genetics; Blood Proteins - immunology; CAP37 protein; Capsules; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - immunology; Correlation analysis; Glycosaminoglycans; Heparin; Humans; Immunity; lactoferrin; Lactoferrin - chemistry; meningococcal disease; Meningococcal Infections - immunology; Meningococcal Infections - prevention & control; Meningococcal Vaccines - chemistry; Meningococcal Vaccines - genetics; Meningococcal Vaccines - immunology; Neisseria meningitidis; Neisseria meningitidis - immunology; Neisseria meningitidis - pathogenicity; protective antigen; Proteinase; Proteins; Survival; Vaccination; Virulence factors; Virulence Factors - chemistry; Virulence Factors - genetics; Virulence Factors - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0915162107

GNA2132 is a Neisseria meningitidis antigen of unknown function, discovered by reverse vaccinology, which has been shown to induce bactericidal antibodies in animal models. Here we show that this antigen induces protective immunity in humans and it is recognized by sera of patients after meningococcal disease. The protein binds heparin in vitro through an Arg-rich region and this property correlates with increased survival of the unencapsulated bacterium in human serum. Furthermore, two proteases, the meningococcal NalP and human lactoferrin, cleave the protein upstream and downstream from the Arg-rich region, respectively. We conclude that GNA2132 is an important protective antigen of N. meningitidis and we propose to rename it, Neisserial Heparin Binding Antigen (NHBA).