Characterization of natural bactericidal antibody against Haemophilus influenzae type a in Canadian First Nations: A Canadian Immunization Research Network (CIRN) Clinical Trials Network (CTN) study

• Published in: PloS one Vol. 13; no. 8; p. e0201282
• Main Authors: Nix, Eli B, Choi, Joshua, Anthes, Christina, Gaultier, Gabrielle N, Thorgrimson, Joelle, Cox, Andrew D, Tsang, Raymond S W, McCready, William G, Boreham, Douglas, Ulanova, Marina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.08.2018; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Adults; Age Factors; Aged; Aged, 80 and over; Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens; Bacterial infections; Bactericidal activity; Biology and Life Sciences; Blood Bactericidal Activity - drug effects; Blood Bactericidal Activity - immunology; Canada; Capsular polysaccharides; Children; Clinical trials; Communities; DNA methylation; Female; Geriatrics; Haemophilus Infections - blood; Haemophilus Infections - immunology; Haemophilus Infections - prevention & control; Haemophilus influenzae; Haemophilus influenzae - immunology; Haemophilus Vaccines - administration & dosage; Haemophilus Vaccines - immunology; Health care; Humans; Immunization; Immunoglobulin G; Immunoglobulin G - biosynthesis; Immunoglobulin G - immunology; Immunoglobulin M; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunoglobulins; Infections; Lipooligosaccharides; Male; Medical research; Medicine; Medicine and Health Sciences; Meningitis; Middle Aged; Native North Americans; Older people; Pathogens; People and places; Polysaccharides; Population studies; Public health; Research and Analysis Methods; Serum bactericidal activity; Vaccines; Canada; Thunder Bay Ontario Canada; Alaska; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0201282

During the last two decades, Haemophilus influenzae serotype a (Hia) emerged as an important cause of invasive disease in Canadian First Nations and Inuit, and Alaskan Native populations, with the highest rates reported in young children. Immunocompetent adults, in contrast to children, do not typically develop invasive Hia disease. To clarify factors responsible for an increased burden of invasive Hia disease in certain population groups we studied serum bactericidal activity (SBA) against Hia and quantified IgG and IgM specific to Hia capsular polysaccharide in healthy adult members of two First Nations communities: 1) with reported cases of invasive Hia disease (Northern Ontario, NO), and 2) without reported cases (Southern Ontario, SO), in comparison to non-First Nations living in proximity to the NO First Nations community, and non-First Nations elderly non-frail Canadians from across the country (total of 110 First Nations and 76 non-First Nations). To elucidate the specificity of bactericidal antibodies, sera were absorbed with various Hia antigens. Naturally acquired SBA against Hia was detected at higher rates in First Nations (NO, 80%; SO, 96%) than non-First Nations elderly Canadians (64%); the SBA titres in First Nations were higher than in non-First Nations elderly Canadians (P<0.001) and NO non-First Nations adults (P>0.05). Among First Nations, SBA was mediated predominantly by IgM, and by both antibodies specific to Hia capsular polysaccharide and lipooligosaccharide. The SBA against Hia is frequently present in sera of First Nations adults regardless of the burden of Hia disease observed in their community; it may represent part of the natural antibody repertoire, which is potentially formed in this population under the influence of certain epigenetic factors. Although the nature of these antibodies deserves further studies to understand their origin, the data suggest that they may represent important protective mechanism against invasive Hia disease.