Search Results (145)

Background/Objectives: African Swine Fever (ASF), caused by the African Swine Fever Virus (ASFV), is a highly contagious and lethal disease in pigs, for which no recognized safe and effective vaccine is currently available. The ASFV EP153R gene, expressed during both early and late infection stages, exhibits strong protective potential. Utilizing advances in genetic engineering, recombinant PRRSV vector vaccines carrying ASFV exogenous genes were constructed. This study aims to prepare pEP153R-based polyclonal antibodies and an iELISA detection method using the constructed rPRRSV-EP153R as a specific target to verify the iELISA’s specificity and effectiveness. Methods: A prokaryotic plasmid, pCold-TF-EP153R, was constructed to express protein in BL21 (DE3). The purified soluble protein (2 mg/mL) was used to generate a murine polyclonal antibody and establish an indirect ELISA. The EP153R gene was inserted between ORF1b and ORF2a of PRRSV via reverse genetics, yielding recombinant rPRRSV-EP153R. Its biological properties were assessed in vitro and in vivo. Results: The pEP153R was specifically detected by both anti-His antibody and generated polyclonal antibodies. An established iELISA showed high specificity, sensitivity, and 98.18% accuracy. The antibodies specifically recognized pEP153R expressed in recombinant virus and eukaryotic systems. Additionally, the recombinant virus stably maintained EP153R without changes in virological characteristics relative to vHuN4-F112. In vaccinated piglets, the rPRRSV-EP153R induced a specific, consistent, and detectable immune response. Conclusions: The established iELISA, characterized by high specificity, sensitivity, and accuracy, furnishes reliable technical support for the serological diagnosis of ASFV. Meanwhile, the recombinant virus rPRRSV-EP153R demonstrates potential as a novel live vectored vaccine candidate, with the capability to induce specific immunity against both ASFV and PRRSV. Full article

Background: Classical swine fever virus (CSFV) is a highly contagious and fatal disease in pigs and wild boars. While hunting and bait vaccination are effective for CSFV eradication, additional strategies are needed to control wild boar populations. This study aimed to develop an oral vaccine, Flc-LOM-GnRHx3, by inserting gonadotropin-releasing hormone (GnRH) epitopes into the Flc-LOM clone. Methods: The Flc-LOM-GnRHx3 strain was rescued from CPK cells and propagated to high titers in MDBK cells. Male boars (20 weeks old) received three doses (10^5.0 TCID₅₀/ml/dose) of Flc-LOM-GnRHx3 either orally or intramuscularly at 2-week intervals. Anti-CSFV E2 antibodies were detected via immunofluorescence and Western blotting. Results: Both vaccination routes induced anti-GnRH antibodies and reduced testosterone levels. Testis size and weight were slightly lower than controls, with seminiferous tubule and spermatid deformities observed in 52.5% of intramuscularly vaccinated pigs and 20.8% of orally vaccinated pigs. Conclusions: Flc-LOM-GnRHx3 demonstrates potential as a dual-function oral vaccine that can eradicate CSFV and impair reproductive capacity in wild boars, offering a novel approach for integrated disease control and population management. Full article

Orthoflaviviruses belong to the flavivirus genus, which is part of the Flaviviridae family. Orthoflaviviruses include major clinically relevant arthropod-borne human viruses such as Dengue, Zika, yellow fever, West Nile and tick-borne encephalitis virus. These viruses pose an increasing threat to global health due to the expansion of arthropod habitats, urbanization, and climate change. While vaccines have been developed for certain orthoflaviviruses with varying levels of success, critical challenges remain in achieving broadly deployable vaccines that combine a robust safety profile with durable immunity against many current and emerging orthoflaviviruses. This review provides a snapshot of established and emerging vaccine platforms against orthoflaviviruses, with a particular emphasis on those leveraging the envelope glycoprotein E as the primary antigen. We examine the strengths and disadvantages of these different platforms in eliciting safe, durable, and robust orthoflavivirus immunity, and discuss how specific attributes such as multivalency, authentic epitope presentations, and logistical practicality can enhance their value in preventing orthoflavivirus infection and disease. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is one of the leading infectious causes of adult mortality worldwide. The Bacillus Calmette–Guérin (BCG) vaccine is currently the only approved vaccine for TB prevention, but its protective efficacy against adult pulmonary TB is limited, and it lacks effective protection against primary or latent TB infection. There is an urgent need to develop more effective preventive TB vaccines. Currently, preventive TB vaccines under clinical investigation globally include live attenuated vaccines, recombinant subunit vaccines, viral vector vaccines, and mRNA vaccines. This article reviews and summarizes recent progress in the clinical development of preventive TB vaccines, analyzing and comparing their safety, immunogenicity, and protective efficacy. It also explores novel strategies for next-generation TB vaccine development, aiming to provide insights and directions for future research. Full article

This study reviews the role of epidemiology in the United States in the late 19th and early 20th century, which led to recognition that poliomyelitis is an infectious disease and set the stage for subsequent developments in virology and immunology, the development of inactivated and live attenuated polio vaccines, and a dramatic worldwide decrease in poliomyelitis mortality and morbidity. Epidemiological studies in the United States were systematically reviewed from the mid-19th to early 20th centuries. Isolated cases and scattered small outbreaks of poliomyelitis in the mid-19th century led to epidemics of increasing size by the end of the century, causing public consternation, especially as the disease was considered “new” and had a predilection for young children. By the 1890s, the seasonal pattern of epidemics suggested that poliomyelitis might have an infectious etiology, but direct evidence of communicability or contagiousness was lacking, so an infectious etiology was not widely suspected until the early 20th century. Reports of bacterial isolations from spinal fluid and postmortem tissues suggested that poliomyelitis might be a bacterial disease, and simultaneous outbreaks of paralytic disease in humans and animals suggested a possible zoonotic basis. Although experimental studies showed that it was theoretically possible for flies to serve as vectors of poliovirus, and occasional cases of polio were likely caused by fly-borne transfer of poliovirus from human feces to human food, a fly abatement field trial showed convincingly that flies, whether biting or non-biting, could not explain the bulk of cases during polio epidemics. In conclusion, the early application of epidemiological evidence beginning in the late 19th century strongly suggested the infectious nature of the disease, distinct from previously identified conditions. Subsequent advances in virology and immunology from 1909 to 1954 proved that poliomyelitis was a viral disease with no natural animal host and made feasible the development of an inactivated trivalent poliovirus vaccine by Salk, and, subsequently, a live-attenuated trivalent poliovirus vaccine by Sabin. Full article

Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8⁺ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article

Avian influenza A viruses (IAVs) pose a persistent threat to the poultry industry, causing substantial economic losses. Although traditional vaccines have helped reduce the disease burden, they typically rely on multivalent antigens, emphasize humoral immunity, and require intensive production. This study aimed to establish a genetically matched host–cell system to evaluate antigen-specific immune responses and identify conserved CD8+ T cell epitopes in avian influenza viruses. To this end, we developed an MHC class I genotype (B21)-matched host (Lohmann VALO SPF chicken) and cell vector (DF-1 cell line) model. DF-1 cells were engineered to express the hemagglutinin (HA) gene of clade 2.3.4.4b H5N1 either transiently or stably, and to stably express the matrix 1 (M1) and nucleoprotein (NP) genes of A/chicken/South Korea/SL20/2020 (H9N2, Y280-lineage). Following prime-boost immunization with HA-expressing DF-1 cells, only live cells induced strong hemagglutination inhibition (HI) and virus-neutralizing (VN) antibody titers in haplotype-matched chickens. Importantly, immunization with DF-1 cells transiently expressing NP induced stronger IFN-γ production than those expressing M1, demonstrating the platform’s potential for differentiating antigen-specific cellular responses. CD8+ T cell epitope mapping by mass spectrometry identified one distinct MHC class I-bound peptide from each of the HA-, M1-, and NP-expressing DF-1 cell lines. Notably, the identified HA epitope was conserved in 97.6% of H5-subtype IAVs, and the NP epitope in 98.5% of pan-subtype IAVs. These findings highlight the platform’s utility for antigen dissection and rational vaccine design. While limited by MHC compatibility, this approach enables identification of naturally presented epitopes and provides insight into conserved, functionally constrained viral targets. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Background: Modern viral vector production needs to consider process intensification for higher yields from smaller production volumes. However, innate antiviral immunity triggered in the producer cell may limit virus replication. While commonly used cell lines (e.g., Vero or E1A-immortalised cells) are already compromised in antiviral pathways, the redundancy of innate signaling complicates host cell optimization by genetic engineering. Small molecules that are hypothesized to target antiviral pathways (Viral Sensitizers, VSEs) added to the culture media offer a versatile alternative to genetic modifications to increase permissiveness and, thus, viral yields across multiple cell lines. Methods: To explore how the yield for a chimeric Zika vaccine candidate (YF-ZIK) could be further be increased in an intensified bioprocess, we used spin tubes or an Ambr15 high-throughput microbioreactor system as scale-down models to optimize the dosing for eight VSEs in three host cell lines (AGE1.CR.pIX, BHK-21, and HEK293-F) based on their tolerability. Results: Addition of VSEs to an already optimized infection process significantly increased infectious titers by up to sevenfold for all three cell lines tested. The development of multi-component VSE formulations using a design of experiments approach allowed further synergistic titer increases in AGE1.CR.pIX cells. Scale-up to 1 L stirred-tank bioreactors and 3D-printed mimics of 200 or 2000 L reactors resulted in up to threefold and eightfold increases, respectively. Conclusions: Addition of single VSEs or combinations thereof allowed a further increase in YF-ZIK titers beyond the yield of an already optimized, highly intensified process. The described approach validates the use of VSEs and can be instructive for optimizing other virus production processes. Full article

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has substantially reduced the global incidence of these diseases. However, live attenuated vaccines raise concerns regarding safety and immunogenicity, especially in immunocompromised populations, while recombinant subunit vaccines, such as Shingrix, exhibit high efficacy but are associated with side effects and adjuvant limitations. Recent advancements in vaccine technology, including mRNA vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines, offer promising alternatives with improved safety profiles and durable immunity. This review synthesizes current knowledge on VZV vaccine mechanisms, clinical applications, and immunization strategies, while also examining future directions in vaccine development. The findings underscore the pivotal role of VZV vaccines in disease prevention and highlight the need for continued research to enhance their public health impact. Full article

Over the past decade, diseases associated with fowl adenoviruses (FAdVs) have exhibited a new epidemic trend worldwide. The presence of numerous FAdVs serotypes, combined with the virus’s broad host range, positions it as a significant pathogen in the poultry industry. In the current context of intensive poultry production and global trade, co-infections involving multiple FAdVs serotypes, as well as co-infections with FAdVs alongside infectious bursal disease or infectious anemia virus, may occur within the same region or even on the same farm. The frequency of these outbreaks complicates the prevention and control of FAdVs. Therefore, the development of effective, targeted vaccines is essential for providing technical support in the management of FAdVs epidemics. Ongoing vaccine research aims to improve vaccine efficacy and address the challenges posed by emerging FAdVs outbreaks. This review focuses on vaccines developed and studied worldwide for various serotypes of FAdVs in the past decade. It encompasses inactivated vaccines, live attenuated vaccines, e.g., host-adapted attenuated vaccines and gene deletion vaccines, viral vector vaccines, and subunit vaccines (including VLP proteins and chimeric proteins). The current limitations and future development directions of FAdVs vaccine development are also proposed to provide a reference for new-generation vaccines and innovative vaccination strategies against FAdVs, as well as for the rapid development of highly effective vaccines. Full article

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine efficacy, necessitating ongoing surveillance and vaccine adaptation. Current SARS-CoV-2 vaccines, including inactivated, live-attenuated, viral vector, protein subunit, virus-like particle, and nucleic acid vaccines, face challenges due to the immune evasion strategies of emerging variants. Moreover, other sarbecoviruses, such as SARS-CoV-1 and SARS-related coronaviruses (SARSr-CoVs) pose a potential risk for future outbreaks. Thus, developing vaccines capable of countering emerging SARS-CoV-2 variants and providing broad protection against multiple sarbecoviruses is imperative. Several innovative vaccine platforms are being investigated to elicit broad-spectrum neutralizing antibody responses, offering protection against both current SARS-CoV-2 variants and other sarbecoviruses. This review presents an updated overview of the key target antigens and therapeutic strategies employed in current SARS-CoV-2 vaccines. Additionally, we summarize ongoing approaches for the development of vaccines targeting infectious sarbecoviruses. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has rapidly evolved, giving rise to multiple Variants of Concern—including Alpha, Beta, Gamma, Delta, and Omicron—which emerged independently across different regions. Licensed COVID-19 vaccines primarily target the highly mutable spike protein, resulting in reduced efficacy due to immune escape by emerging variants. Previously, we developed a live attenuated Francisella tularensis LVS ΔcapB single-vector platform COVID-19 vaccine, rLVS ΔcapB/MN, expressing the conserved membrane (M) and nucleocapsid (N) proteins from the early SARS-CoV-2 WA-01/2020 strain. In this study, we evaluate the efficacy of rLVS ΔcapB/MN and an enhanced version, rLVS ΔcapB::RdRp/MN, which additionally expresses the conserved RNA-dependent RNA polymerase (RdRp) protein from the same strain, in a hamster model. Methods: Both vaccine candidates were administered orally or intranasally to golden Syrian hamsters (equal numbers of males and females) and evaluated against intranasal challenge with SARS-CoV-2 Delta (B.1.617.2-AY.1) and Omicron (BA.5) variants. Results: Vaccinated animals developed robust, TH1-biased IgG responses specific to the nucleocapsid protein. Following SARS-CoV-2 challenge, immunized hamsters exhibited reduced weight loss, lower oropharyngeal and lung viral titers, and improved lung pathology scores compared with unvaccinated controls. Conclusion: These findings support the potential of this universal vaccine to provide broad protection against current and future SARS-CoV-2 variants, with minimal need for updating. Full article

Rodents represent the most diverse order of mammals, comprising over 2200 species and nearly 42% of global mammalian biodiversity. They are major reservoirs of zoonotic pathogens, including viruses, bacteria, protozoa, and fungi, and are particularly effective at transmitting diseases, especially synanthropic species that live in close proximity to humans. As of April 2025, approximately 15,205 rodent-associated viruses have been identified across 32 viral families. Among these, key zoonotic agents belong to the Arenaviridae, Hantaviridae, Picornaviridae, Coronaviridae, and Poxviridae families. Due to their adaptability to both urban and rural environments, rodents serve as efficient vectors across diverse ecological landscapes. Environmental and anthropogenic factors, such as climate change, urbanization, deforestation, and emerging pathogens, are increasingly linked to rising outbreaks of rodent-borne diseases. This review synthesizes current knowledge on rodent-borne viral zoonoses, focusing on their taxonomy, biology, host associations, transmission dynamics, clinical impact, and public health significance. It underscores the critical need for early detection, effective surveillance, and integrated control strategies. A multidisciplinary approach, including enhanced vector control, improved environmental sanitation, and targeted public education, is essential for mitigating the growing threat of rodent-borne zoonoses to global health. Full article

Influenza (flu) is a highly prevalent respiratory illness caused by influenza viruses, representing a significant global health burden due to its substantial morbidity and mortality rate. Vaccination remains the most effective strategy for influenza prevention, and well-characterized animal models of influenza infection serve as essential tools for evaluating vaccine protective efficacy. However, animal models utilizing live influenza virus strains pose significant biosafety concerns, and many such strains are not readily available for research. To address these challenges, we established a novel visual mouse infection model using an HIV-based vector system. This model employs influenza pseudoviruses carrying a luciferase reporter gene, enabling real-time monitoring of viral load and in vivo tracking of viral distribution during infection. Using this infection model, we assessed the in vivo protective efficacy of an influenza vaccine and cross-validated the pseudovirus-based evaluation results against a live virus-infected mouse model. Our study thus establishes a safer and more convenient platform for evaluating influenza vaccine efficacy, including the assessment of broad-spectrum neutralization capacity. Full article