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Update on Campylobacter vaccine development.

ABSTRACT: Background: Acute diarrheal disease caused by viral, bacterial and parasitic infections are a major global health problem with substantial mortality and morbidity in children under five years of age in lower and middle income countries. However, a number of these infections also impact large segments of populations in upper income countries, as well as individuals who travel overseas for work, business or pleasure. Campylobacter has been and continues to be a leading cause of disease burden globally across all income countries. Aims: The aim of this review is to describe recent understanding in burden of disease, consider the current landscape of Campylobacter vaccine development, and address the challenges that need to be overcome. Sources: Relevant data from the literature as well as clinical trials described in European and US registries were used to conduct this review. Content: Despite advances in population health, food security, improved sanitation, water quality and the reduction of poverty, Campylobacter infections continue to plague global populations. The emerging recognition of chronic health consequences attributed to this pathogen is changing the potential valuation of preventive interventions. Advancing development of new vaccines is a present opportunity and holds promise.

SUBMITTER: Poly F

PROVIDER: S-EPMC6663129 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Update on Campylobacter vaccine development.

Poly Frédéric F Noll Alexander J AJ Riddle Mark S MS Porter Chad K CK

Human vaccines & immunotherapeutics 20181017 6

Background: Acute diarrheal disease caused by viral, bacterial and parasitic infections are a major global health problem with substantial mortality and morbidity in children under five years of age in lower and middle income countries. However, a number of these infections also impact large segments of populations in upper income countries, as well as individuals who travel overseas for work, business or pleasure. Campylobacter has been and continues to be a leading cause o ...[more]

PMID: 30252591

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Project description:Campylobacter jejuni is the leading bacterial cause of human enteritis in many industrialized countries. There is no commercial vaccine against C. jejuni available to date. CmeC is an essential outer membrane component of CmeABC multidrug efflux pump that plays a critical role in antibiotic resistance and in vivo colonization of C. jejuni. CmeC is prevalent in C. jejuni strains and is dramatically induced and immunogenic in vivo. In this study, we analyzed CmeC sequence homology, examined in vitro immune protection of CmeC peptide antibodies, and produced full-length recombinant CmeC (rCmeC) for evaluating immunogenicity and protective efficacy of the CmeC subunit vaccine against C. jejuni using chicken model system. Amino acid sequences of CmeC from 24 diverse C. jejuni strains were determined and subjected to alignment, which revealed that CmeC is highly conserved in C. jejuni with a identity ranging from 97.3% to 100%. CmeC peptide antibodies inhibited the function of CmeABC efflux pump and enhanced susceptibility of C. jejuni to bile salts, the natural antimicrobial present in the intestine. Two full-length rCmeC proteins with N- or C-terminal His tag were produced in E. coli; the N-terminal His-tagged rCmeC with high purity and yield was obtained by single step affinity purification. The purified rCmeC was used in two vaccination trials using a chicken model of C. jejuni infection. Stimulation of CmeC-specific serum IgG responses via oral vaccination required immunization with higher doses of rCmeC (200μg) together with 70μg of mucosal adjuvant mLT (modified E. coli heat-labile enterotoxin). Subcutaneous vaccination of chickens with rCmeC remarkably stimulated both serum IgG and IgA responses. However, CmeC-specific intestinal secretory IgA response was not significantly stimulated regardless of vaccination regimen and the rCmeC vaccination did not confer protection against C. jejuni infection. Together, these findings provide further compelling evidence that CmeC is a promising subunit vaccine candidate against C. jejuni infection. However, the CmeC vaccination regimen should be optimized to enhance CmeC-specific mucosal immune response in for protection against C. jejuni.

Project description:Campylobacter jejuni (C. jejuni) is one of the major pathogens contributing to the enteritis in humans. Infection can lead to numerous complications, including but not limited to Guillain-Barre syndrome, reactive arthritis, and Reiter's syndrome. Over the past two decades, joint efforts have been made toward developing a proper strategy of limiting the transmission of C. jejuni to humans. Nevertheless, except for biosecurity measures, no available vaccine has been developed so far. Judging from the research findings, Omp18, AhpC outer membrane protein, and FlgH flagellin subunits of C. jejuni could be adopted as surface protein antigens of C. jejuni for screening dominant epitope thanks to their strong antigenicity, expression of varying strains, and conservative sequence. In this study, bioinformatics technology was adopted to analyze the T-B antigenic epitopes of Omp18, AhpC, and FlgH in C. jejuni strain NCTC11168. Both ELISA and Western Blot methods were adopted to screen the dominant T-B combined epitope. GGS (GGCGGTAGC) sequence was adopted to connect the dominant T-B combined epitope peptides and to construct the prokaryotic expression system of tandem repeats of antigenic epitope peptides. The mouse infection model was adopted to assess the immunoprotective effect imposed by the trivalent T-B combined with antigen epitope peptide based on Omp18/AhpC/FlgH. In this study, a tandem epitope AhpC-2/Omp18-1/FlgH-1 was developed, which was composed of three epitopes and could effectively enhance the stability and antigenicity of the epitope while preserving its structure. The immunization of BALB/c mice with a tandem epitope could induce protective immunity accompanied by the generation of IgG2a antibody response through the in vitro synthesis of IFN-γ cytokines. Judging from the results of immune protection experiments, the colonization of C. jejuni declined to a significant extent, and it was expected that AhpC-2/Omp18-1/FlgH-1 could be adopted as a candidate antigen for genetic engineering vaccine of C. jejuni MAP.

Project description:The 2011 EFSA opinion on Campylobacter was updated using more recent scientific data. The relative risk reduction in EU human campylobacteriosis attributable to broiler meat was estimated for on-farm control options using Population Attributable Fractions (PAF) for interventions that reduce Campylobacter flock prevalence, updating the modelling approach for interventions that reduce caecal concentrations and reviewing scientific literature. According to the PAF analyses calculated for six control options, the mean relative risk reductions that could be achieved by adoption of each of these six control options individually are estimated to be substantial but the width of the confidence intervals of all control options indicates a high degree of uncertainty in the specific risk reduction potentials. The updated model resulted in lower estimates of impact than the model used in the previous opinion. A 3-log10 reduction in broiler caecal concentrations was estimated to reduce the relative EU risk of human campylobacteriosis attributable to broiler meat by 58% compared to an estimate larger than 90% in the previous opinion. Expert Knowledge Elicitation was used to rank control options, for weighting and integrating different evidence streams and assess uncertainties. Medians of the relative risk reductions of selected control options had largely overlapping probability intervals, so the rank order was uncertain: vaccination 27% (90% probability interval (PI) 4-74%); feed and water additives 24% (90% PI 4-60%); discontinued thinning 18% (90% PI 5-65%); employing few and well-trained staff 16% (90% PI 5-45%); avoiding drinkers that allow standing water 15% (90% PI 4-53%); addition of disinfectants to drinking water 14% (90% PI 3-36%); hygienic anterooms 12% (90% PI 3-50%); designated tools per broiler house 7% (90% PI 1-18%). It is not possible to quantify the effects of combined control activities because the evidence-derived estimates are inter-dependent and there is a high level of uncertainty associated with each.

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Update on Campylobacter vaccine development.

Publications

Update on Campylobacter vaccine development.

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