RESUMO
The holistic view of food and feed safety, including animal health and environmental conditions, is an important pillar of the One Health approach. The terminology thus clearly goes beyond the prevention of spreading microbiological diseases, in which context it is often understood, and highlights that humans, animals, and the environment as well as their interaction should be considered in a transdisciplinary context.In terms of One Health, this discussion paper focuses less on microbiological risks, but rather on the connection to chemical risks in the food chain. This is illustrated by concrete examples of chemical contaminants (metals, persistent organic contaminants, natural toxins). The mechanisms of input and transfer along the food chain are presented.Minimizing the presence of contaminants and thus exposure requires international and interdisciplinary cooperation in the spirit of the One Health approach. Climate change, pandemics, shortages of raw materials, energy deficiencies, political crises, and environmental disasters can affect the entire food chain from primary production of plant and animal foods to further processing and provision of products to consumers. In addition to changing availability, this can also have an impact on the composition, quality, and safety of food and feed. Based on the effect on global commodity chains, vulnerable and resilient areas along the food chain become visible. In terms of the One Health approach, the aim is to increase safety and resilience along the food chain and to minimize its vulnerability.
Assuntos
Saúde Única , Humanos , Animais , Alemanha , Ração Animal , Cadeia Alimentar , Contaminação de Alimentos/análise , Inocuidade dos AlimentosRESUMO
Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L) protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.
Assuntos
Vetores Genéticos/química , Antígenos de Superfície da Hepatite B/imunologia , Compostos de Piridínio/química , Células Th1/imunologia , Vacinas de DNA/imunologia , Animais , Células CHO , Cátions , Cricetulus , Feminino , Vacinas contra Hepatite B/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , SuínosRESUMO
We have previously shown that the combination of MIDGE-Th1 DNA vectors with the cationic lipid SAINT-18 increases the immune response to the encoded antigen in mice. Here, we report on experiments to further optimize and characterize this approach. We evaluated different formulations of MIDGE-Th1 vectors with SAINT-18 by assessing their influence on the transfection efficiency in cell culture and on the immune response in mice. We found that high amounts of SAINT-18 in formulations with a w/w ratio MIDGE Th1/SAINT-18 of 1:4.8 are beneficial for cell transfection in vitro. In contrast, the formulation of HBsAg-encoding MIDGE-Th1 DNA vectors with the lowest amount of SAINT-18 (w/w ratio MIDGE Th1/SAINT-18 of 1:0.5) resulted in the highest serum IgG1 and IgG2a levels after intradermal immunization of mice. Consequently, latter formulation was selected for a comparative biodistribution study in rats. Following intradermal administration of both naked and formulated MIDGE-Th1 DNA, the vectors localized primarily at the site of injection. Vector DNA levels decreased substantially over the two months duration of the study. When administered in combination with SAINT-18, the vectors were found in significantly higher amounts in draining lymph nodes in comparison to administration of naked MIDGE-Th1 DNA. We propose that the high immune responses induced by MIDGE-Th1/SAINT-18 lipoplexes are mediated by enhanced transfection of cells in vivo, resulting in stronger antigen expression and presentation. Importantly, the combination of MIDGE-Th1 vectors with SAINT-18 was well tolerated in mice and rats and is expected to be safe in human clinical applications.
Assuntos
Vetores Genéticos/química , Compostos de Piridínio/química , Vacinas de DNA/imunologia , Animais , Anticorpos Antivirais/sangue , Cátions , Feminino , Vetores Genéticos/farmacocinética , Antígenos de Superfície da Hepatite B/imunologia , Imunoglobulina G/sangue , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos de Piridínio/farmacocinética , Ratos , Ratos Wistar , Células Th1/imunologia , Distribuição Tecidual , Transfecção , Vacinas de DNA/farmacocinéticaRESUMO
Human pathogenic Chlamydia trachomatis have evolved sophisticated mechanisms to manipulate host cell signalling pathways in order to prevent apoptosis. We show here that host cells infected with C. trachomatis resist apoptosis induced by polyI:C, a synthetic double-stranded RNA that mimics viral infections. Infected cells displayed significantly reduced levels of PARP cleavage, caspase-3 activation and a decrease in the TUNEL positive population in the presence of polyI:C. Interestingly, the chlamydial block of apoptosis was upstream of the initiator caspase-8. Processing of caspase-8 was reduced in infected cells and coincided with a decrease in Bid truncation and downstream caspase-9 cleavage. Moreover, the enzymatic activity of caspase-8, measured by a luminescent substrate, was significantly reduced in infected cells. Caspase-8 inhibition by Chlamydia was dependent on cFlip as knock-down of cFlip decreased the chlamydial block of caspase-8 activation and consequently reduced apoptosis inhibition. Our data implicate that chlamydial infection interferes with the host cell's response to viral infections and thereby influences the fate of the cell.