The Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis vaccine that has the ability to induce non-specific cross-protection against pathogens that might be unrelated to the target disease. Vaccination with BCG reduces mortality in newborns and induces an improved innate immune response against microorganisms other than Mycobacterium tuberculosis, such as Candida albicans and Staphylococcus aureus. Innate immune cells, including monocytes and natural killer (NK) cells, contribute to this non-specific immune protection in a way that is independent of memory T or B cells. This phenomenon associated with a memory-like response in innate immune cells is known as “trained immunity.” Epigenetic reprogramming through histone modification in the regulatory elements of particular genes has been reported as one of the mechanisms associated with the induction of trained immunity in both, humans and mice. Indeed, it has been shown that BCG vaccination induces changes in the methylation pattern of histones associated with specific genes in circulating monocytes leading to a “trained” state. Importantly, these modifications can lead to the expression and/or repression of genes that are related to increased protection against secondary infections after vaccination, with improved pathogen recognition and faster inflammatory responses. In this review, we discuss BCG-induced cross-protection and acquisition of trained immunity and potential heterologous effects of recombinant BCG vaccines.
The obligate intracellular bacterium is the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions of, including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models.
The human respiratory syncytial virus (hRSV) is the main etiologic agent of severe lower respiratory tract infections that affect young children throughout the world, associated with significant morbidity and mortality, becoming a serious public health problem globally. Up to date, no licensed vaccines are available to prevent severe hRSV-induced disease, and the generation of safe-effective vaccines has been a challenging task, requiring constant biomedical research aimed to overcome this ailment. Among the difficulties presented by the study of this pathogen, it arises the fact that there is no single animal model that resembles all aspects of the human pathology, which is due to the specificity that this pathogen has for the human host. Thus, for the study of hRSV, different animal models might be employed, depending on the goal of the study. Of all the existing models, the murine model has been the most frequent model of choice for biomedical studies worldwide and has been of great importance at contributing to the development and understanding of vaccines and therapies against hRSV. The most notable use of the murine model is that it is very useful as a first approach in the development of vaccines or therapies such as monoclonal antibodies, suggesting in this way the direction that research could have in other preclinical models that have higher maintenance costs and more complex requirements in its management. However, several additional different models for studying hRSV, such as other rodents, mustelids, ruminants, and non-human primates, have been explored, offering advantages over the murine model. In this review, we discuss the various applications of animal models to the study of hRSV-induced disease and the advantages and disadvantages of each model, highlighting the potential of each model to elucidate different features of the pathology caused by the hRSV infection.
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