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Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.Cancer: Boosting the right signals to suppress tumorsTumor cells killed by radiotherapy or chemotherapy release signaling molecules that stimulate both immune response and tumor aggressiveness; regulating these molecules could improve treatment efficacy. Tae Heung Kang, Yeong-Min Park, and co-workers at Konkuk University, Seoul, South Korea, have reviewed the role of damage-associated molecular patterns (DAMPs) in immunity and cancer. These signaling molecules act as danger signals, activating immune cells by binding to specific receptors. However, tumor cells have the same receptors, and DAMPs binding triggers chemoresistance and increases invasiveness. The researchers report that although DAMPs can trigger a helpful immune response, they can also cause chronic inflammation, which in turn promotes an immune suppression response, allowing tumors to escape immune detection. Improving our understanding of the functions of different DAMPs could improve our ability to boost the immune response and decrease tumor aggressiveness.

Modernization of existing methods for the delivery of mRNA is vital in advanced therapeutics. Traditionally, mRNA has faced obstacles of poor stability due to enzymatic degradation. This work examines cutting-edge formulation and emerging techniques for safer delivery of mRNA vaccines. Inspired by the success of lipid nanoparticles (LNP) in delivering mRNA vaccines for COVID-19, a variety of other formulations have been developed to deliver mRNA vaccines for diverse infections. The meritorious features of nanoparticle-based mRNA delivery strategies, including LNP, polymeric, dendrimers, polysaccharide-based, peptide-derived, carbon and metal-based, DNA nanostructures, hybrid, and extracellular vesicles, have been examined. The impact of these delivery platforms on mRNA vaccine delivery efficacy, protection from enzymatic degradation, cellular uptake, controlled release, and immunogenicity has been discussed in detail. Even with significant developments, there are certain limitations to overcome, including toxicity concerns, limited information about immune pathways, the need to maintain a cold chain, and the necessity of optimizing administration methods. Continuous innovation is essential for improving delivery systems for mRNA vaccines. Future research directions have been proposed to address the existing challenges in mRNA delivery and to expand their potential prophylactic and therapeutic application.

Combination vaccines provide the versatile benefits of addressing different pathogens simultaneously using a combined formulation. This approach can be regarded as a substantial modernization in immunization. In this review, we highlight various advancements in combination vaccines based on mRNA, viral vectors, live attenuated, and recombinant vaccines. Recent success in clinical trials of mRNA platforms for combination vaccines has particularly accelerated research in this direction. The advantages of combination vaccines in terms of patient adherence, cost effectiveness, and streamlined immunization schedule are discussed. The existing challenges of antigenic interference, logistical hurdles, and the complications of regulatory standards are analyzed. Research trends to make combination vaccines viable for emerging infections have been summarized. The current work provides a critical overview, the existing opportunities, and the future prospects of combination vaccines.

Zoonotic viruses have significant pandemic potential, as evidenced by the coronavirus pandemic, which underscores that zoonotic infections have historically caused numerous outbreaks and millions of deaths over centuries. Zoonotic viruses induce numerous types of illnesses in their natural hosts. These viruses are transmitted to humans via biological vectors, direct contact with infected animals or their bites, and aerosols. Zoonotic viruses continuously evolve and adapt to human hosts, resulting in devastating consequences. It is very important to understand pathogenesis pathways associated with zoonotic viral infections across various hosts and develop countermeasure strategies accordingly. In this review, we briefly discuss advancements in diagnostics and therapeutics for zoonotic viral infections. It provides insight into recent outbreaks, viral dynamics, licensed vaccines, as well as vaccine candidates progressing to clinical investigations. Despite advancements, challenges persist in combating zoonotic viruses due to immune evasion, unpredicted outbreaks, and the complexity of the immune responses. Most of these viruses lack effective treatments and vaccines, relying entirely on supportive care and preventive measures. Exposure to animal reservoirs, limited vaccine access, and insufficient coverage further pose challenges to preventive efforts. This review highlights the critical need for ongoing interdisciplinary research and collaboration to strengthen preparedness and response strategies against emerging infectious threats.

Emerging infectious diseases (EIDs) are one of the greatest threats to human health today, thus requiring an urgent response. Vaccines are one of the most effective means of preventing the spread of infectious diseases, and their usefulness in responding to EIDs has been clearly proven through the process of overcoming the global COVID-19 pandemic. As the characteristics of various vaccine formulations differ, it is necessary to apply the most appropriate one according to the EID response strategy. In this review, we first consider which vaccine formulation is the most suitable for EID vaccines by comparing the pros and cons of different vaccine formulations, and then we discuss the utility of mRNA vaccine formulations, which are considered the most promising for EID vaccines.

The Nipah virus (NiV) is a zoonotic pathogen characterized by high fatality rates and pandemic potential, whereby there is an urgent need for developing safe and effective vaccines. However, the evaluation of NiV vaccine-induced immunity is hindered by the requirement of Biosafety Level-4 (BSL-4) containment. In this study, we developed a recombinant vesicular stomatitis virus (rVSV)-based pseudovirus-expressing NiV fusion (F) and attachment (G) glycoproteins using a luciferase reporter gene for bioluminescence detection. This pseudovirus was optimized for production in BHK-21 (WI-2) cells, and simultaneous incorporation of NiV-F and NiV-G onto the surface of the pseudotyped virus was confirmed via immunoprecipitation and Western blotting. We evaluated our pseudovirus-based neutralization assay using NiV-F-immunized mouse sera and a commercial anti-NiV-G antibody, confirming robust neutralization by the latter. To establish a BSL-2-compatible model for evaluating in vivo protective efficacy, we performed in vivo imaging, which revealed a marked reduction in the luminescence signal in NiV-G-immunized mice compared to naïve controls, indicating vaccine-induced protection. Our study established an integrated in vitro and in vivo pseudovirus platform using rVSV that enables safe, quantitative, and BSL-2-compatible evaluation of NiV vaccine candidates. This model offers a valuable tool for preclinical screening of vaccine-induced neutralizing antibody responses and protective efficacy.

Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public health worldwide. Although the timely development and production of mRNA and adenoviral vector vaccines against SARS-CoV-2 have been successful, issues still exist in vaccine platforms for wide use and production. With the potential for proliferative capability and heat stability, the Newcastle disease virus (NDV)-vectored vaccine is a highly economical and conceivable candidate for treating emerging diseases. In this study, a recombinant NDV-vectored vaccine expressing the spike (S) protein of SARS-CoV-2, rK148/beta-S, was developed and evaluated for its efficacy against SARS-CoV-2 in K18-hACE-2 transgenic mice. Intramuscular vaccination with low dose (106.0 EID50) conferred a survival rate of 76 % after lethal challenge of a SARS-CoV-2 beta (B.1.351) variant. When administered with a high dose (107.0 EID50), vaccinated mice exhibited 100 % survival rate and reduced lung viral load against both beta and delta variants (B.1.617.2). Together with the protective immunity, rK148/beta-S is an accessible and cost-effective SARS-CoV-2 vaccine.

The current production of the Japanese encephalitis virus (JEV) vaccine is based on animal cells, where various risk factors for human health should be resolved. This study used a transient expression system to express the chimeric protein composed of antigenic epitopes from the JEV envelope (E) protein in Nicotiana benthamiana. JEV multi-epitope peptide (MEP) sequences fused with FLAG-tag or 6× His-tag at the C- or N-terminus for the purification were introduced into plant expression vectors and used for transient expression. Among the constructs, vector pSK480, which expresses MEP fused with a FLAG-tag at the C-terminus, showed the highest level of expression and yield in purification. Optimization of transient expression procedures further improved the target protein yield. The purified MEP protein was applied to an ICR mouse and successfully induced an antibody against JEV, which demonstrates the potential of the plant-produced JEV MEP as an alternative vaccine candidate.

The complete genome sequence of a new polerovirus found naturally infecting Artemisia princeps, artemisia virus B (ArtVB), was determined using high-throughput sequencing. The ArtVB genome comprises 6,141 nucleotides and contains six putative open reading frames (ORF0 to ORF5) with a genome structure typical of poleroviruses. A multiple sequence alignment showed that the complete ArtVB genome shares 50.98% nucleotide sequence identity with ixeridium yellow mottle virus 1 (IxYMaV-1, GenBank accession no. KT868949). ArtVB shares the highest amino acid sequence identity in P0 and P3–P5 (21.54%–51.69%) with other known poleroviruses. Phylogenetic analysis indicated that ArtVB should be considered a member of a new species within the genus Polerovirus, family Luteoviridae.

In order to develop a successful vaccine against deadly diseases with a wide range of antigenic diversity, an in-depth knowledge of the molecules and signaling mechanisms between the vaccine candidates and immune cells is required. Therefore, monitoring vaccine components, such as antigen or adjuvants, and immune cell dynamics at the vaccination site or draining lymph nodes can provide important information to understand more about the vaccine response. This review briefly introduces and describes various non-invasive molecular imaging methods for visualizing immune cell dynamics after vaccination.