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Naturally occurring bactericidal antibodies specific for Haemophilus influenzae Lipooligosaccharide are present in healthy adult individuals
Institution:1. Department of Biology, Lakehead University, Thunder Bay, ON, Canada;2. Vaccine Program, Human Health Therapeutics, National Research Council, Ottawa, ON, Canada;3. Northern Ontario School of Medicine, Thunder Bay, ON, Canada;1. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation;2. Department of General Microbiology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, 90-237 Lodz, Poland;1. Department of Otorhinolaryngology-HNS, The Second Affiliated Hospital, Xi’an Jiaotong University, School of Medicine, Xi’an 710049, China;2. Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA;1. Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark;2. Department of Pulmonary Medicine, Hvidovre Hospital, Hvidovre, Denmark;3. Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;1. Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA;2. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA;3. Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA;1. Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Fla;2. Division of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Chicago, Ill;3. Division of Allergy-Immunology, James A. Haley Veterans'' Hospital, Tampa, Fla;4. Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
Abstract:Nontypeable Haemophilus influenzae (NTHi), a typical mucosal pathogen largely responsible for respiratory infections and pediatric otitis media, has been increasingly recognized as a significant cause of invasive disease, especially in immunocompromised individuals. Lipooligosaccharide (LOS) is a conserved molecule with an important role in H. influenzae virulence and immune evasion, and it may be considered as a vaccine candidate. However, abilities of H. influenzae LOS to induce protective immune response are poorly understood. The goal of this study was to determine whether antibodies against LOS isolated from H. influenzae strains Eagan, Rd and NTHi 375 are present in the sera of normal individuals. Antigen specific IgG and IgM were studied in sera of 71 and 30 healthy adults, respectively. IgG specific for LOS of all three strains was ubiquitously present in our sample population while IgM specific for Eagan, Rd and NTHi 375 LOS compounds was detected in 37%, 63%, and 40% of samples, respectively. All tested serum samples exhibited bactericidal activity against all three H. influenzae strains; the removal of anti-LOS antibodies from the sera resulted in significant increases in bacterial survival of the corresponding strain. NTHi 375 exhibited the highest serum resistance, whereas the Rd strain was the least resistant. Serum bactericidal activity of anti-LOS antibody was mediated via the classical complement pathway. These findings suggest that in healthy adults, naturally acquired complement-activating anti-LOS antibodies significantly contribute to the overall serum bactericidal activity against both encapsulated and non-encapsulated strains of H. influenzae.
Keywords:NTHi  LOS  Serum resistance  Adaptive response  Bactericidal antibody  BAFF  APRIL
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