Dataset Information

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.

ABSTRACT: 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.

Conclusions

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.

SUBMITTER: Nix EB

PROVIDER: S-EPMC6093645 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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.

Nix Eli B EB Choi Joshua J Anthes Christina C Gaultier Gabrielle N GN Thorgrimson Joelle J Cox Andrew D AD Tsang Raymond S W RSW McCready William G WG Boreham Douglas D Ulanova Marina M

PloS one 20180815 8

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 ...[more]

PMID: 30110339

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Project description:BackgroundNunavut, the northernmost Arctic territory of Canada, experienced three community outbreaks of the coronavirus disease 2019 (COVID-19) from early November 2020 to mid-June 2021. We sought to investigate how non-pharmaceutical interventions (NPIs) and vaccination affected the course of these outbreaks.MethodsWe used an agent-based model of disease transmission to simulate COVID-19 outbreaks in Nunavut. The model encapsulated demographics and household structure of the population, the effect of NPIs, and daily number of vaccine doses administered. We fitted the model to inferred, back-calculated infections from incidence data reported from October 2020 to June 2021. We then compared the fit of the scenario based on case count data with several counterfactual scenarios without the effect of NPIs, without vaccination, and with a hypothetical accelerated vaccination program whereby 98% of the vaccine supply was administered to eligible individuals.ResultsWe found that, without a territory-wide lockdown during the first COVID-19 outbreak in November 2020, the peak of infections would have been 4.7 times higher with a total of 5,404 (95% CrI: 5,015-5,798) infections before the start of vaccination on January 6, 2021. Without effective NPIs, we estimated a total of 4,290 (95% CrI: 3,880-4,708) infections during the second outbreak under the pace of vaccination administered in Nunavut. In a hypothetical accelerated vaccine rollout, the total infections during the second Nunavut outbreak would have been 58% lower, to 1,812 (95% CrI: 1,593-2,039) infections. Vaccination was estimated to have the largest impact during the outbreak in April 2021, averting 15,196 (95% CrI: 14,798-15,591) infections if the disease had spread through Nunavut communities. Accelerated vaccination would have further reduced the total infections to 243 (95% CrI: 222-265) even in the absence of NPIs.ConclusionsNPIs have been essential in mitigating pandemic outbreaks in this large, geographically distanced and remote territory. While vaccination has the greatest impact to prevent infection and severe outcomes, public health implementation of NPIs play an essential role in the short term before attaining high levels of immunity in the population.

Project description:Non-typeable Haemophilus influenzae (NTHi), a commensal organism in pre-school children, is an opportunistic pathogen causing respiratory tract infections including acute otitis media. Adults suffering from chronic obstructive pulmonary disease (COPD) are persistently colonized by NTHi. Previous research has suggested that, in some bacterial species, the intracellular elongation factor thermo-unstable (EF-Tu) can moonlight as a surface protein upon host encounter. The aim of this study was to determine whether EF-Tu localizes to the surface of H. influenzae, and if such surface-associated EF-Tu is a target for bactericidal antibodies. Using flow cytometry, transmission immunoelectron microscopy, and epitope mapping, we demonstrated that EF-Tu is exposed at the surface of NTHi, and identified immunodominant epitopes of this protein. Rabbits immunized with whole-cell NTHi produced significantly more immunoglobulin G (IgG) directed against EF-Tu than against the NTHi outer membrane proteins D and F as revealed by enzyme-linked immunosorbent assays. Chemical cleavage of NTHi EF-Tu by cyanogen bromide (CNBr) followed by immunoblotting showed that the immunodominant epitopes were located within the central and C-terminal regions of the protein. Peptide epitope mapping by dot blot analysis further revealed four different immunodominant peptide sequences; EF-Tu41-65, EF-Tu161-185, EF-Tu221-245, and EF-Tu281-305. These epitopes were confirmed to be surface-exposed and accessible by peptide-specific antibodies in flow cytometry. We also analyzed whether antibodies raised against NTHi EF-Tu cross-react with other respiratory tract pathogens. Anti-EF-Tu IgG significantly detected EF-Tu on unencapsulated bacteria, including the Gram-negative H. parainfluenzae, H. haemolyticus, Moraxella catarrhalis and various Gram-positive Streptococci of the oral microbiome. In contrast, considerably less EF-Tu was observed at the surface of encapsulated bacteria including H. influenzae serotype b (Hib) and Streptococcus pneumoniae (e.g., serotype 3 and 4). Removal of the capsule, as exemplified by Hib RM804, resulted in increased EF-Tu surface density. Finally, anti-NTHi EF-Tu IgG promoted complement-dependent bacterial killing of NTHi and other unencapsulated Gram-negative bacteria as well as opsonophagocytosis of Gram-positive bacteria. In conclusion, our data demonstrate that NTHi EF-Tu is surface-exposed and recognized by antibodies mediating host innate immunity against NTHi in addition to other unencapsulated respiratory tract bacteria.

Dataset Information

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.

Conclusions

Publications

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.

Similar Datasets

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