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Companion Animals Models of Human Disease
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
A complex biological system is often required to study the myriad of host-pathogen interactions associated with infectious diseases, especially since the current basis of biology has reached the molecular level. The use of animal models is important for understanding the very complex temporal relationships that occur in infectious disease involving the body, its neuroendocrine and immune systems, and the infectious organism. Because of these complex interactions, the choice of animal model must be a thoughtful and clearly defined process in order to provide relevant, translatable scientific data and to ensure the most beneficial use of the animals. While many animals respond similarly to humans from physiological, pathological, and therapeutic perspectives, there are also significant species-by-species differences. A well-designed animal model requires a thorough understanding of similarities and differences in the responses between humans and animals and incorporates that knowledge into the goals of the study. Determining the intrinsic and extrinsic factors associated with the disease and creating a biological information matrix to compare the animal model and human disease courses is a useful tool to help choose the appropriate animal model. Confidence in the correlation of results from a model to the human disease can be achieved only if the relationship of the model to the human disease is well understood(116,117).
Disease Prediction and Drug Development
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
Host–pathogen interaction is a complex phenomenon involving factors such as gene transfers between two bacteria, antigen–receptor interaction, antigen–antibody interaction, release of toxins by the pathogens and evasion of the pathogens from the immune system. Gene-expression analysis has been used for biomarker discovery by identifying a minimal cluster of highly correlated uniquely coexpressed gene-clusters. GWAS and linkage analysis have been used to predict susceptibility to the genetic diseases. However, infectious diseases and the disruptions in the signaling pathways caused by the foreign-body invasions cannot be predicted by GWAS and require gene-expression analysis.
Klebsiella: Caenorhabditis elegans as a Laboratory Model for Klebsiella pneumoniae Infection
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Arumugam Kamaladevi, Krishnaswamy Balamurugan
Generally, foodborne infections induce a wide spectrum of symptoms. Although the actual incidence of gastrointestinal infection is largely unknown, the risk of getting infection through heavily contaminated food is probably high [4]. To eradicate the foodborne illness, public health awareness is critical. Since the study based on volunteers feeding does not represent a feasible option, the understanding of K. pneumoniae infection is chiefly based on epidemiological data, infection case reports, and use of animal models. An ideal animal model should mimic all phases of the human disease condition, as the host–pathogen interaction in a natural biological condition reveals the host’s resistance mechanism and virulence properties of pathogen that promote colonization and subsequent dissemination [4].
An overview of human leptospirosis vaccine design and future perspectives
Published in Expert Opinion on Drug Discovery, 2020
Carolina R. Felix, Bianca S. Siedler, Liana N. Barbosa, Gabriana R. Timm, Johnjoe McFadden, Alan J. A. McBride
However, it is not all doom and gloom. For this review, we collated all of the published data associated with recombinant vaccines for leptospirosis since 1999 and we have been able to draw several conclusions that should aid the discovery and development of vaccines candidates toward the goal of a universal vaccine. We also note that the discovery phase for the identification of novel antigens has been significantly improved with the use of the techniques such as RV, SV, CSIP; together with epitope mapping of the surface-exposed domains of these proteins. We should also recognize that there are significant knowledge gaps in the basic microbiology of Leptospira spp., including host–pathogen interactions. However, this field is rapidly evolving, and the availability of hundreds of genomes should be of benefit. Nevertheless, the meaningful interpretation of this data represents a potential holdup that will slow progress. A large number of leptospiral genes, including virulence factors, do not have an assigned function and many are unique to Leptospira spp. with no known orthologues in other bacteria [103,104]. The functional characterization of these proteins will provide much needed information and could identify additional vaccine candidates. The application of a systems biology approach would greatly aid our understanding and provide new targets for possible interventions. In addition, we now know that post-translation modifications occur in Leptospira spp. and this will likely have a major impact on the production of the recombinant proteins used in vaccine preparations. However, unless we can identify in vitro assays to screen the hundreds of proteins that have and will be identified, there will be a serious bottleneck between discovery and the evaluation of these potential vaccine candidates.
Selection of adjuvants for vaccines targeting specific pathogens
Published in Expert Review of Vaccines, 2019
Indranil Sarkar, Ravendra Garg, Sylvia van Drunen Littel-van den Hurk
Recent advancements have allowed researchers to conclude that clinical-grade adjuvants have distinct immunological profiles and signatures, which can be used to target different pathogens. Based on pathogen-specific immune response requirements (i.e. Th1, Th2 or Th17 responses, or mixed Th1/Th2 or Th1/Th17 responses, etc.), next-generation adjuvants can be rationally developed and incorporated into human vaccines. Currently, all approved human adjuvants mostly induce only antibody responses. However, recent adjuvant research has led to the development of novel adjuvants capable of inducing CMI (especially required for malaria, TB and HIV), as well as antibody responses. New immunostimulatory adjuvants or immunomodulatory compounds are under investigation to induce CMI and high antibody titers. Novel combination adjuvants are being tested in candidate human vaccines with promising results that have strong implications for use in vaccines against challenging infectious pathogens and different target populations. This is potentially due to activation of multiple innate immune sensing signal transduction pathways by combination adjuvants. Novel adjuvants are required that can target emerging new pathogens or re-emerging old pathogens. Such pathogens often have a more complex host–pathogen interaction, which needs better understanding and further characterization. Among these new-generation adjuvants, several are proprietary, which may make it difficult to purchase them and conduct independent parallel trials. Factors such as genetic background, pre-exposure to pathogens or vaccine antigens, age, nutritional and immunological status of vaccine recipients, all dictate the final effectiveness of adjuvanted vaccines. Nevertheless, with the aid of structural, systems and reverse vaccinology, epitope prediction and other technological advancements, adjuvant technology is now gradually progressing towards a more personalized approach.
Chapter 2: Transmission and pathogenesis of tuberculosis
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2022
Richard Long, Maziar Divangahi, Kevin Schwartzman
The pathogenesis and transmission of TB are inter-related. M. tuberculosis is almost exclusively a human pathogen and how it interacts with the human host determines its survival. From the perspective of the bacterium, a successful host-pathogen interaction is one that results in ongoing pathogen transmission.56