Naturally occurring bactericidal antibodies specific for Haemophilus influenzae lipooligosaccharide are present in healthy adult individuals.
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.
Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
Joshua
J
Choi
Northern Ontario School of Medicine, Thunder Bay, ON, Canada.
Eli B
EB
Nix
Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
Gabrielle N
GN
Gaultier
Vaccine Program, Human Health Therapeutics, National Research Council, Ottawa, ON, Canada.
Andrew D
AD
Cox
Northern Ontario School of Medicine, Thunder Bay, ON, Canada.
William
W
McCready
Department of Biology, Lakehead University, Thunder Bay, ON, Canada; Northern Ontario School of Medicine, Thunder Bay, ON, Canada. Electronic address: Marina.Ulanova@nosm.ca.
Marina
M
Ulanova
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D001770:Blood Bactericidal Activity; D002460:Cell Line; D015870:Gene Expression; D006192:Haemophilus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008875:Middle Aged; D011159:Population Surveillance; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D053264:B-Cell Activating Factor; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C023023:lipid-linked oligosaccharides
APRIL; Adaptive response; BAFF; Bactericidal antibody; LOS; NTHi; Serum resistance