Search Results (21,488)

Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there is no cure or vaccine. Initial or recurrent HSV infection can produce serious complications and mediate acquisition of HIV. This review outlines the initial events after the HSV infection of human anogenital mucosa to determine the optimal window to target the virus before it becomes latent. After infection, HSV spreads rapidly within the mid-layers of epidermal keratinocytes in the explanted human inner foreskin. Infected cells produce chemokines, which modulate nectin-1 distribution on the surface of adjacent keratinocytes, facilitating viral spread. Epidermal Langerhans cells and dendritic cells become infected with HSV followed by a “viral relay” to dermal MNPs, which then present viral antigen to T cells in the dermis or lymph nodes. These data indicate the need for interruption of spread within 24 h by diffusible vaccine-induced mediators such as antiviral cytokines from resident immune cells or antibodies. Intradermal/mucosal vaccines would need to target the relevant dermal MNPs to induce HSV-specific CD4⁺ and CD8⁺ T cells. Full article

Genital herpes simplex virus (HSV) is associated with a reduction in quality of life and adverse outcomes. The aim of this study is to assess the interest and expectations for a therapeutic HSV vaccine among individuals diagnosed with genital herpes in Italy. A retrospective survey was conducted at the Infectious Diseases Unit of the IRCCS San Raffaele Scientific Institute, Milan, Italy. The study collected data on demographics, clinical history and interest in HSV vaccination. The results showed that 87.5% of participants were interested in a therapeutic vaccine, with interest higher among younger people and those with frequent genital herpes recurrences. Participants most expected the vaccine to reduce the pain associated with outbreaks, followed by a reduction in the frequency and duration of recurrences. These findings underscore the strong demand for a therapeutic HSV vaccine, especially among those who experience recurrent outbreaks, and highlight the importance of considering patient expectations when developing preventive and therapeutic strategies for genital herpes. Full article

The development of effective vaccines necessitates a delicate balance between maximizing immunogenicity and minimizing safety concerns. Subunit vaccines, while generally considered safe, often fail to elicit robust and durable immune responses. Nanotechnology presents a promising approach to address this dilemma, enabling subunit antigens to mimic critical aspects of native pathogens, such as nanoscale dimensions, geometry, and highly repetitive antigen display. Various expression systems, including Escherichia coli (E. coli), yeast, baculovirus/insect cells, and Chinese hamster ovary (CHO) cells, have been explored for the production of nanoparticle vaccines. Among these, E. coli stands out due to its cost-effectiveness, scalability, rapid production cycle, and high yields. However, the E. coli manufacturing platform faces challenges related to its unfavorable redox environment for disulfide bond formation, lack of post-translational modifications, and difficulties in achieving proper protein folding. This review focuses on molecular and protein engineering strategies to enhance protein solubility in E. coli and facilitate the in vitro reassembly of virus-like particles (VLPs). We also discuss approaches for antigen display on nanocarrier surfaces and methods to stabilize these carriers. These bioengineering approaches, in combination with advanced nanocarrier design, hold significant potential for developing highly effective and affordable E. coli-derived nanovaccines, paving the way for improved protection against a wide range of infectious diseases. Full article

Tick-borne encephalitis (TBE) is a vaccine-preventable viral infection that poses significant public health challenges, particularly in regions where tick-borne diseases are endemic. This case report describes a 2-year-old boy with confirmed abortive TBEV infection following a tick bite during travel to Switzerland. The patient developed fever and mild symptoms but did not exhibit central nervous system involvement. The case underscores the importance of raising awareness among healthcare providers and travelers from non-endemic areas, such as Serbia, about TBE risk and the potential benefits of preventive vaccination. Strategic immunization campaigns could mitigate the public health impact of travel-related TBE. Full article

Pandemics of infectious disease and growing anti-microbial resistance (AMR) pose major threats to global health, trade, and security. Conflict and climate change compound and accelerate these threats. The One Health approach recognizes the interconnectedness of human, animal, and environmental health, but is grounded in the biomedical model, which reduces health to the absence of disease. Biomedical responses are insufficient to meet the challenges. The COVID-19 pandemic is the most recent example of the failure of this biomedical model to address global threats, the limitations of laboratory-based surveillance, and the exclusive focus on vaccination for disease control. This paper examines the current paradigm through the lens of polio and the global campaign to eradicate it, as well as other infectious threats including mpox and drug-resistant tuberculosis, particularly in the context of armed conflict. Decades before vaccines became widely available, public health measures—ventilation, chlorination, nutrition and sanitation— led to longer, healthier, and even taller lives. Chlorine, our primary tool of public health, conquered cholera and transformed infection control in hospitals. The World Health Organization (WHO), part of the One Health alliance, focuses mainly on antibiotics and vaccines to reduce deaths due to superbugs and largely ignores the critical role of chlorine to control water-borne diseases (including polio) and other infections. Moreover, the One Health approach ignores armed conflict. Contemporary wars are characterized by indiscriminate bombing of civilians, attacks targeting healthcare, mass displacement and lack of humanitarian access, conditions which drive polio outbreaks and incubate superbugs. We discuss the growing trend of attacks on healthcare and differentiate between types: community-driven attacks targeting vaccinators in regions like Pakistan, and state-sponsored attacks by governments such as those of Syria and Russia that weaponize healthcare to deliberately harm whole populations. Both fuel outbreaks of disease. These distinct motivations necessitate tailored responses, yet the WHO aggregates these attacks in a manner that hampers effective intervention. While antimicrobial resistance is predictable, the escalating pandemic is the consequence of our reliance on antibiotics and commitment to a biomedical model that now borders on pathological. Our analysis reveals the international indenture to the biomedical model as the basis of disease control is the root driver of AMR and vaccine-derived polio. The unique power of vaccines is reduced by vaccination-only strategy, and in fact breeds vaccine-derived polio. The non-specific effects of vaccines must be leveraged, and universal vaccination must be supplement by international investment in water chlorination will reduce health costs and strengthen global health security. While vaccines are an important weapon to combat pandemics and AMR,, they must be accompanied by the entire arsenal of public health interventions. Full article

Background/Objectives: Infectious bronchitis (IB) is a highly infectious avian disease caused by the infectious bronchitis virus (IBV). The disease causes lesions mainly in the respiratory, reproductive, and renal systems and has a significant economic impact on the poultry industry worldwide. Methods: We discovered two unique IBV isolates (T-62: PP737794.1 and CL-61: PP783617.1) circulating in Canada and molecularly characterized them. Results: The phylogenetic analysis revealed that the IBV isolates belong to genotype I and fall between lineages 25 and 7. Further analysis of the T-62 IBV isolate indicated that it is a potential recombinant of the Iowa state isolate (IA1162/2020-MW) and that the CL-61 strain of the IBV is also a recombinant IBV with the Connecticut (Conn) vaccine strain as its major parent. The S1 glycoprotein of the CL-61 and T-62 strains of the IBV had 85.7% and 73.2% amino acid (aa) identities respectively compared to the Conn vaccine strain. There were 67 and 129 aa substitutions among the S1 glycoprotein of the CL-61 and T-62 strains of the IBV compared to the Conn vaccine, respectively. Importantly, two and nineteen of these aa variations were in hypervariable regions 1 (HVR1) and HVR3. Finally, the two IBV isolates possessed a higher affinity for the sialic acid ligand compared to the DMV/1639 and Mass/SES IBV strains. Conclusions: Genetic recombination in the IBV results in the continual emergence of new variants, posing challenges for the poultry industry. As indicated by our analyses, live attenuated vaccine strains play a role in the genetic recombination of the IBV, resulting in the emergence of variants. Full article

Background: The evaluation of HPV vaccine effectiveness is essential for informing public health strategies, yet there remains a gap in understanding humoral immune responses generated by different HPV vaccine formulations in regional populations. This study addresses this gap by evaluating the immunogenicity of the newly developed HPV vaccine Cecolin (Wantai), alongside various imported vaccines, including bivalent, quadrivalent, and nonavalent options available in China. Methods: From March 2023 to June 2024, a total of 352 participants were enrolled, including 87 females aged 9–14 years who received two doses of the bivalent HPV vaccine (Cecolin), 215 females aged 15–45 years who were fully vaccinated with various HPV vaccines, and 50 non-recipients. Follow-up assessments were conducted at six timepoints during the administration of Cecolin. Serum was collected at enrollment and at each follow-up visit for antibody assessments using a pseudovirion-based neutralization assay (PBNA). Findings: The longitudinal follow-up of females aged 9–14 years revealed a 100% conversion rate for neutralizing antibodies against HPV types 16 and 18 after the second dose, compared to 94.3% and 97.1% conversion rates six months after the first dose. Compared to participants who received full doses of quadrivalent and nonavalent vaccines, females who received two or three doses of Cecolin exhibited higher neutralizing antibody geometric mean titers (GMTs) and non-vaccine-type (HPV31 and HPV33) antibody seroconversion rates. Interpretation: The domestically produced HPV vaccine Cecolin in China demonstrates strong immunogenicity and holds promise for the large-scale vaccination of females in developing countries to prevent cervical cancer. Full article

Introduction: Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection. Viral surveillance for early detection of COVID-19 is a critical strategy to understand this population’s infection dynamics and prevent transmission. The study examines SARS-CoV-2 infection and reinfection among HCWs vaccinated against COVID-19 working at a primary healthcare unit serving a disenfranchised community in Brazil. Methods: The study was conducted in Cidade Estrutural, Federal District, Brazil, between February and October 2021. Participants were interviewed and provided samples. A prospective open cohort study was used to analyze the frequency of SARS-CoV-2 infection and reinfection, and the vaccine-induced seroconversion. Nasopharyngeal swab specimen was collected from workers presenting with flu-like symptoms and subjected to RT-qPCR. Peripheral blood samples were also collected every 30 ± 2 days for eight months, starting from the day participants received their first dose of COVID-19 vaccine, and submitted to serological testing (IgM and IgG chemiluminescence). The frequencies of infection and reinfection (RT-qPCR positive results 90 days after the infection) were calculated along with their respective confidence intervals (95% CI). Results: Of the 128 workers, 61 (47.65%; CI: 39.19–56.25) reported probable SARS-CoV-2 infection before vaccination and 50 (39.06%; CI: 31.04–47.71) had SARS-CoV-2 infection after vaccination, confirmed by molecular test. Reinfection was identified in seven workers (7/50, 14%; CI: 6.95–26.18) based on the 90-day interval between results. The serological data from the 128 workers during the cohort indicated that 68 (53.12%; CI: 44.5–61.5) had IgG antibodies and 46 had IgM antibodies (35.93%; CI: 28.14–44.54) against SARS-CoV-2. SARS-CoV-2 infection was common in 56% of the community health workers (CHWs), 50% of registered nurses, and licensed vocational nurses (33%). Following the COVID-19 vaccination, the percentage of infections among HCWs decreased from 47.83% to 4.35%. Conclusion: These results demonstrate that (i) approximately 40% of the workers were infected with SARS-CoV-2 in 2021 and (ii) reinfections confirmed by RT-qPCR occurred in 14% of the HCWs after vaccination. The results provide valuable insights into the circulation of SARS-CoV-2 among HCWs in a primary care unit serving a minoritized community. Full article

The mutational drift of SARS-CoV-2 and the appearance of multiple variants, including the latest Omicron variant and its sub-lineages, has significantly reduced (and in some cases abolished) the protective efficacy of Wuhan spike-antigen-based vaccines and therapeutic antibodies. One of the most functionally constrained and thus largely invariable regions of the spike protein is the one involved in the interaction with the ACE2 receptor mediating the cellular entry of SARS-CoV-2. Engineered ACE2, both as a full-length protein or as an engineered polypeptide fragment, has been shown to be capable of preventing the host-cell binding of all viral variants and to be endowed with potent SARS-CoV-2 neutralization activity both in vitro and in vivo. Here, we report on the biochemical and antiviral properties of rationally designed ACE2 N-terminal, three-helix fragments that retain a native-like conformation. One of these fragments, designated as PRP8_3H and produced in recombinant form, bears structure-stabilizing and binding-affinity enhancing mutations in α-helix-I and in both α-helix I and II, respectively. While the native-like, unmodified three α-helices ACE2 fragment proved to be thermally unstable and without any detectable pseudovirion neutralization capacity, PRP8_3H was found to be highly thermostable and capable of binding to the SARS-CoV-2 spike receptor-binding domain with nanomolar affinity and to neutralize both Wuhan and Omicron spike-expressing pseudovirions at (sub)micromolar concentrations. PRP8_3H thus lends itself as a highly promising ACE2 decoy prototype suitable for a variety of formulations and prophylactic applications. Full article

Alzheimer’s disease (AD) is a global health concern and the leading cause of dementia in the elderly. The prevalence of this neurodegenerative condition is projected to increase concomitantly with increased life expectancy, resulting in a significant economic burden. With very few FDA-approved disease-modifying drugs available for AD, there is an urgent need to develop new compounds capable of impeding the progression of the disease. Given the unclear etiopathogenesis of AD, this review emphasizes the underlying mechanisms of this condition. It explores not only well-studied aspects, such as the accumulation of Aβ plaques and neurofibrillary tangles, but also novel areas, including glymphatic and lymphatic pathways, microbiota and the gut–brain axis, serotoninergic and autophagy alterations, vascular dysfunction, the metal hypothesis, the olfactory pathway, and oral health. Furthermore, the potential molecular targets arising from all these mechanisms have been reviewed, along with novel promising approaches such as nanoparticle-based therapy, neural stem cell transplantation, vaccines, and CRISPR-Cas9-mediated genome editing techniques. Taking into account the overlap of these various mechanisms, individual and combination therapies emerge as the future direction in the AD strategy. Full article

Background and Objectives: Leprosy primarily affects peripheral nerves, leading to significant neurological complications such as polyneuritis, mononeurosis, and autonomic dysfunction, which contribute to severe disabilities and impaired quality of life for patients. This scoping review aims to investigate the neurological manifestations and main treatments of leprosy patients. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases. This review has been registered on OSF (n) PQBYH. Results: Neurological complications of leprosy, such as neuropathy and paralysis, necessitate accurate diagnosis and treatment, as immunological reactions can exacerbate nerve damage. Various studies highlight the effectiveness of personalized therapies, such as corticosteroids, multi-drug therapy (MDT), and surgical interventions, in improving symptoms and neurological function in leprosy patients. Conclusions: Managing neurological complications of leprosy necessitates careful diagnosis and treatment, as many patients experience unresolved peripheral neuropathy despite multidrug therapy. Future research should focus on improving diagnostic tools, exploring the link between neuropathic pain and psychological issues, and developing effective vaccines and treatments to enhance patient outcomes. Full article

Background: The WHO classified the mpox outbreak as a worldwide health emergency. Increasing the contribution of healthcare providers, such as pharmacists, can enhance preventive efforts. Assessing the knowledge and confidence levels of pharmacists in diagnosing and managing mpox cases can shape the response strategies necessary for the management of such outbreaks. Methods: This research employed a cross-sectional survey designed to assess the knowledge and preparedness of pharmacy students and pharmacists in the United Arab Emirates (UAE) regarding the mpox virus outbreak. Independent researchers evaluated the survey items to confirm the face and content validity of the developed survey. The final study’s survey was structured into three distinct sections, each addressing a specific area of interest. Data were analyzed using the IBM SPSS Statistics. Results: The 388 participants had a median age of 22.00 years (IQR = 5.00). The survey revealed that participants primarily relied on the WHO reports for mpox information (79.8%). The total knowledge scores (TK score) varied, ranging from −6 to 23 (median = 6.00), and symptom knowledge scores (SK score) ranged from −3 to 9 (median = 2.00). Older participants (p-value = 0.008) and females (p-value = 0.014) exhibited significantly higher TK scores. Only about 31.0% of participants expressed confidence in diagnosing mpox cases, and 34.6% expressed confidence in managing mpox cases. Nearly a quarter of the participants (24.5%) thought that getting vaccinated against COVID-19 led to contracting mpox more likely, whereas 45.7% believed that a previous infection with COVID-19 increases the risk of having mpox and its associated symptoms. Many respondents (38.7%) expressed their concern that mpox could emerge as the next major epidemic following COVID-19. Conclusion: Although pharmacists and pharmacy students in the UAE are aware of mpox, their knowledge and confidence levels in diagnosing and managing vary significantly. These findings suggest the need for targeted educational programs to enhance the understanding and preparedness of pharmacists to manage and prevent mpox cases. Full article

Background/Objectives: Porcine Circovirus 2 (PCV2) infection poses significant health and economic challenges to the global swine industry. The disease in pigs leads to lymphoid depletion, resulting in immunosuppression and increased susceptibility to co-infections with other bacterial and viral pathogens. This study evaluated the efficacy of two novel recombinant Newcastle disease virus (NDV) strain R2B vectored vaccines that express the cap gene of PCV2 alone and along with the transmembrane and cytoplasmic tail (TMCT) domains of the NDV F gene. The efficacy of the vaccine candidates was studied in mouse and pig models. Methods: Six-week-old BALB/c mice were divided into five groups and immunized intramuscularly three times at 14-day intervals with various vaccine candidates, namely rNDV-R2B-PCVcap-TMCT, rNDV-R2B-PCVcap, and CircoFLEX commercial vaccine, along with controls. Following immunization and PCV2d virus challenge, multiple assays assessed the immune responses in animal trials. In the pig animal trial, pigs were divided into four groups: a control group (PBS), NDV-vectored PCVcap-TMCT group, NDV-vectored-PCVcap group, and CircoFLEX vaccine group. Pigs were immunized intramuscularly twice at 28-day intervals. Blood samples were collected at regular intervals over 70 days to evaluate the humoral and cell-mediated immune responses. Results: Both mice and pigs’ trials indicated that the NDV-vectored PCV2 cap-TMCT vaccine candidate elicited superior immune responses. In mice, the rNDV-R2B-PCVcap-TMCT group showed enhanced humoral and cellular immunity, increased PCV2-specific antibody levels, higher CD4+/CD8+ ratio, elevated IFN-γ and TNF-α levels, decreased IL-10 levels, reduced viral loads, and minimal histopathological changes. In pigs, the NDV-vectored PCVcap-TMCT group demonstrated better antibody responses, cytokine profiles (IFN-γ and IL-10), and higher levels of PCV2-specific neutralizing antibodies against the PCV2a, PCV2b and PCV2d genotypes when compared to other groups. Conclusions: These findings suggest NDV-vectored PCVcap-TMCT vaccine candidate, expressing the cap gene of PCV2 along with the TMCT domain, offers a promising alternative for protecting against PCV2 infection, potentially addressing the challenges posed by emerging PCV2 strains in the swine industry. Full article

RNA therapeutics have undergone remarkable evolution since their inception in the late 1970s, revolutionizing medicine by offering new possibilities for treating previously intractable diseases. The field encompasses various modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), each with unique mechanisms and applications. The foundation was laid in 1978 with the discovery that synthetic oligonucleotides could inhibit viral replication, followed by pivotal developments such as RNA interference’s discovery in 1998. The COVID-19 pandemic marked a crucial turning point, demonstrating the potential of mRNA vaccines and accelerating interest in RNA-based approaches. However, significant challenges remain, including stability issues, delivery to target tissues, potential off-target effects, and immunogenicity concerns. Recent advancements in chemical modifications, delivery systems, and the integration of AI technologies are addressing these challenges. The field has seen notable successes, such as approved treatments for spinal muscular atrophy and hereditary transthyretin-mediated amyloidosis. Looking ahead, RNA therapeutics show promise for personalized medicine approaches, particularly in treating genetic disorders and cancer. The continued evolution of this field, driven by technological innovations and deeper understanding of RNA biology, suggests a transformative impact on future medical treatments. The purpose of this review is to provide a comprehensive overview of the evolution, current state, and prospects of RNA therapeutics. Full article

The urgent need for an effective COVID-19 therapy has propelled the exploration of innovative strategies to combat the fast-mutating SARS-CoV-2 virus. This study attempted to develop nanobodies (Nbs) against the SARS-CoV-2 Omicron variants by redirecting the 1.29 neutralizing Nb, a receptor-binding domain (RBD)-specific Nb that can protect against various SARS-CoV-2 variants other than Omicron, to target SARS-CoV-2 Omicron subvariant BA.5, the variant used for the development of the bivalent vaccine. Error-prone libraries of the 1.29 Nb were constructed. Following two rounds of selection using the functional ligand-binding identification by Tat-based recognition of associating proteins (FLI-TRAP) technique, we rapidly identified two Nbs, namely, C11 and K9, that could target the RBD of the Omicron subvariant BA.5, XBB.1.5, and XBB.1.16 subvariants. Molecular docking provided insights into how these Nbs interact with the RBD of the BA.5 and JN.1 variants. The application of directed evolution via utilization of error-prone PCR and the synthetic E. coli applied in the FLI-TRAP selection method may be a powerful tool for facilitating simple, fast and economical selection to redirect existing antibodies and to generate antibody fragments to target proteins susceptible to autonomous mutation, not only for viral infection but also other diseases, such as cancer. Full article