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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 , such as and . 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.

Human noroviruses (HuNoVs) are the cause of more than 95% of epidemic non-bacterial gastroenteritis worldwide, with some lethal cases. These viral agents affect people of all ages. However, young children and older adults are the highest-risk groups, being affected with the greatest rate of hospitalizations and morbidity cases. HuNoV structural proteins, especially VP1, have been studied extensively. In contrast, the functions of the non-structural proteins of the virus have been undescribed in depth. Studies on HuNoV non-structural proteins have mostly been made by expressing them individually in cultures, providing insights of their functions and the role that they play in HuNoV replication and pathogenesis. This review examines exhaustively the functions of both HuNoV structural and non-structural proteins and their possible role within the viral replicative cycle and the pathogenesis of the virus. It also highlights recent findings regarding the host's innate and adaptive immune responses against HuNoV, which are of great relevance for diagnostics and vaccine development so as to prevent infections caused by these fastidious viruses.

Respiratory syncytial virus (RSV) is the most prevalent viral etiological agent of acute respiratory tract infection. Although RSV affects people of all ages, the disease is more severe in infants and causes significant morbidity and hospitalization in young children and in the elderly. Host factors, including an immature immune system in infants, low lymphocyte levels in patients under 5 years old, and low levels of RSV-specific neutralizing antibodies in the blood of adults over 65 years of age, can explain the high susceptibility to RSV infection in these populations. Other host factors that correlate with severe RSV disease include high concentrations of proinflammatory cytokines such as interleukins (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and thymic stromal lymphopoitein (TSLP), which are produced in the respiratory tract of RSV-infected individuals, accompanied by a strong neutrophil response. In addition, data from studies of RSV infections in humans and in animal models revealed that this virus suppresses adaptive immune responses that could eliminate it from the respiratory tract. Here, we examine host factors that contribute to RSV pathogenesis based on an exhaustive review of infection in humans and in animal models to provide insights into the design of vaccines and therapeutic tools that could prevent diseases caused by RSV.

Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient’s overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.

Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the family and genus. Early reports-previous to 2001-state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses.

Acute gastroenteritis (AGE) has one of the highest rates of morbidity and mortality among children under five years old worldwide. It is estimated that 1.7 billion cases of childhood diarrheal diseases occur annually, leading to up to 443,832 deaths. Approximately 90% of these cases are viral, with human norovirus being the main cause in countries that have implemented rotavirus vaccines. The objective of this study was to describe the prevalence and genetic diversity of norovirus in child outpatients and inpatients under five years old at the Regional Hospital of Antofagasta. From 1 January to 31 October 2019, a total of 121 stool samples were collected to detect the presence of norovirus GI and GII using Taqman™-based real-time RT-PCR. Norovirus RNA was detected in 50 (41.3%) samples, of which 96% were typed as GII.4 Sydney (42% GII.4 Sydney[P16] and 54% GII.4 Sydney[P4 New Orleans]). Furthermore, most (92%) of the positive specimens were from children under two years of age and a majority were detected in April (38%) and May (20%). Our findings highlight the high burden of norovirus in hospitalized children with AGE and the importance of molecular strain surveillance to support vaccine development.

Shark-derived single-domain antibodies, known as VNARs, represent unique and advanced tools in medical biotechnology. Recognized for their small size, simple structure, and exceptional stability, VNARs can access cryptic epitopes that are inaccessible to traditional antibodies, making them valuable tools for next-generation diagnostic and therapeutic applications. Additionally, their evolutionary origin and structural diversity provide resistance to extreme pH, temperature, and proteolytic environments, making them especially suitable for demanding biomedical settings such as ocular and intestinal applications. Recent progress highlights their growing clinical potential: VNAR-based CAR-T cells targeting PD-L1 demonstrated strong anti-tumor effects in preclinical assays, with VNAR-B2 successfully blocking PD-L1/PD-1 interactions and reducing tumor growth in mouse models. Meanwhile, the TXB2 VNAR platform allows efficient, non-invasive transport of biologics across the blood-brain barrier. These developments emphasize VNARs’ advantages over traditional antibodies and even camelid VHHs in targeting difficult-to-reach sites and environments. Additionally, commercial development in VNAR technologies is advancing, with companies like Elasmogen using its soloMER™ platform to develop shark-derived, humanized single-domain antibodies for challenging therapeutic environments. This review consolidates emerging insights into VNAR structural biology, display technologies (phage, ribosome, yeast, and bacterial), and library engineering strategies, emphasizing their growing role in immunodiagnostics, infectious disease detection, targeted therapies, and barrier-crossing biologics. It addresses key translational challenges such as humanization and half-life extension, which are crucial for clinical application, ultimately highlighting the transformative potential of VNARs in bridging vital gaps in modern medicine.

AbstractIntroduction: Patients presenting with encephalopathy and longitudinally extensive myelitis pose a significant diagnostic challenge. Area postrema-related symptoms, such as intractable hiccoughs, can aid in narrowing the differential diagnosis. Neuromyelitis optica spectrum disorders and glial fibrillary acidic protein (GFAP) autoimmune encephalitis are known causes; however, some cases remain seronegative, suggesting the presence of unidentified autoantibodies or immune targets. Case Presentation: A previously healthy man in his 70s presented with headache, fever, and confusion, followed by a seizure and persistent hiccoughs. MRI revealed brainstem involvement and extensive transverse myelitis. Cerebrospinal fluid (CSF) analysis showed inflammatory features, but testing for AQP4, MOG, and GFAP antibodies was initially negative. He was treated with intravenous corticosteroids and plasma exchange, after which serum GFAP-IgG was weakly positive, though CSF remained negative. His condition improved with immunotherapy, but significant lower limb weakness persisted. Based on clinical and radiological findings, we hypothesize that tanycytes – specialized glial cells in the area postrema – may be an additional immune target in GFAP encephalitis. Conclusion: This case highlights a seronegative encephalomyelitis syndrome with area postrema involvement, possibly implicating glial cells beyond astrocytes. Further studies are needed to explore the role of tanycytes in autoimmune neuroinflammation.

Streptococcus pneumoniae is a Gram-positive bacterium and the leading cause of bacterial pneumonia in children and the elderly worldwide. Currently, two types of licensed vaccines are available to prevent the disease caused by this pathogen: the 23-valent pneumococcal polysaccharide-based vaccine and the 7-, 10, 13, 15 and 20-valent pneumococcal conjugate vaccine. However, these vaccines, composed of the principal capsular polysaccharide of leading serotypes of this bacterium, have some problems, such as high production costs and serotype-dependent effectiveness. These drawbacks have stimulated research initiatives into non-capsular-based vaccines in search of a universal vaccine against S. pneumoniae. In the last decades, several research groups have been developing various new vaccines against this bacterium based on recombinant proteins, live attenuated bacterium, inactivated whole-cell vaccines, and other newer platforms. Here, we review and discuss the status of non-capsular vaccines against S. pneumoniae and the future of these alternatives in a post-pandemic scenario.