Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein ...regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations.
In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA.
We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.
While the coronavirus disease (COVID‐19) accounts for the current global pandemic, the emergence of other unknown pathogens, named “Disease X,” remains a serious concern in the future. Emerging or ...re‐emerging pathogens continue to pose significant challenges to global public health. In response, the scientific community has been urged to create advanced platform technologies to meet the ever‐increasing needs presented by these devastating diseases with pandemic potential. This review aims to bring new insights to allow for the application of advanced nanomaterials in future diagnostics, vaccines, and antiviral therapies, thereby addressing the challenges associated with the current preparedness strategies in clinical settings against viruses. The application of nanomaterials has advanced medicine and provided cutting‐edge solutions for unmet needs. Herein, an overview of the currently available nanotechnologies is presented, highlighting the significant features that enable them to control infectious diseases, and identifying the challenges that remain to be addressed for the commercial production of nano‐based products is presented. Finally, to conclude, the development of a nanomaterial‐based system using a “One Health” approach is suggested. This strategy would require a transdisciplinary collaboration and communication between all stakeholders throughout the entire process spanning across research and development, as well as the preclinical, clinical, and manufacturing phases.
Nanomaterials have a significant potential for creating sophisticated complexes, mimicking the natural size and structures of viruses without the complications of toxicity. New approaches for applying advanced nanomaterial‐based platform technologies to future diagnostics, vaccines, and antiviral treatments against emerging infectious diseases are reviewed. The unmet needs and future directions of current nanomaterial‐based tools in the clinical settings are also addressed.
A recurrent pandemic with unpredictable viral nature has implied the need for a rapid diagnostic technology to facilitate timely and appropriate countermeasures against viral infections. In this ...study, conductive polymer-based nanoparticles have been developed as a tool for rapid diagnosis of influenza A (H1N1) virus. The distinctive property of a conductive polymer that transduces stimulus to respond, enabled immediate optical signal processing for the specific recognition of H1N1 virus. Conductive poly(aniline-co-pyrrole)-encapsulated polymeric vesicles, functionalized with peptides, were fabricated for the specific recognition of H1N1 virus. The low solubility of conductive polymers was successfully improved by employing vesicles consisting of amphiphilic copolymers, facilitating the viral titer-dependent production of the optical response. The optical response of the detection system to the binding event with H1N1, a mechanical stimulation, was extensively analyzed and provided concordant information on viral titers of H1N1 virus in 15 min. The specificity toward the H1N1 virus was experimentally demonstrated via a negative optical response against the control group, H3N2. Therefore, the designed system that transduces the optical response to the target-specific binding can be a rapid tool for the diagnosis of H1N1.
The coronavirus disease (COVID-19) pandemic poses serious global health concerns with the continued emergence of new variants. The periodic outbreak of novel emerging and re-emerging infectious ...pathogens has elevated concerns and challenges for the future. To develop mitigation strategies against infectious diseases, nano-based approaches are being increasingly applied in diagnostic systems, prophylactic vaccines, and therapeutics. This review presents the properties of various nanoplatforms and discusses their role in the development of sensors, vectors, delivery agents, intrinsic immunostimulants, and viral inhibitors. Advanced nanomedical applications for infectious diseases have been highlighted. Moreover, physicochemical properties that confer physiological advantages and contribute to the control and inhibition of infectious diseases have been discussed. Safety concerns limit the commercial production and clinical use of these technologies in humans; however, overcoming these limitations may enable the use of nanomaterials to resolve current infection control issues via application of nanomaterials as a platform for the diagnosis, prevention, and treatment of viral diseases.
Considering the urgent demand for reliable and rapid detection of infectious respiratory viruses during unpredictable pandemics, an innovative ultrasensitive colorimetric immunoassay for influenza A ...(H1N1) virus detection is developed herein. The proposed approach leverages dual amplification by combining layer‐by‐layer interactions with the nanozyme effect of biotinylated gold nanoparticles (BGNPs). BGNPs assemble around the target via repeated incubation cycles under optimized conditions, resulting in a layered structure that increases optical density, producing a more intense signal proportional to the viral titer. Additionally, the nanozyme effect of the layered BGNPs induces oxidation of 3,3',5,5'‐tetramethylbenzidine, which further enhances the visible signal detectable by the naked eye. This synergetic nanoprobe‐based system demonstrates remarkable sensitivity, with a limit of detection of 101.29 EID50 mL−1, which is 2500‐fold higher than that of commercial rapid kits and conventional enzyme‐linked immunosorbent assays, within a rapid 55 min timeframe. Furthermore, the anti‐interference capability and portability of the developed system reinforce its practicality, making it a promising tool for field diagnostic tests that offers advanced, ultrasensitive, and early detection of respiratory viruses.
An ultrasensitive and visible detection for influenza A virus is presented by leveraging the properties of gold nanoparticles (GNPs). Dual amplification, achieved through a synthetic nanoprobe utilizing the enzymatic properties of layered GNPs, exhibits a higher sensitivity. This system is suitable for point‐of‐care tests within 55 min by verifying its diagnostic potential using highly portable devices.
Powerful adjuvants to augment vaccine efficacy with a less immunogenic vaccine system are in great demand. In this study, a novel squalene‐based cationic poly(amino acid) adjuvant (CASq) that elicits ...both cellular (Th1) and humoral (Th2) immune responses is developed. CASq is demonstrated to promote cellular uptake of viral antigen and stimulate macrophages, leading to active production of interleukin‐12. Furthermore, co‐administration of inactivated pdm H1N1 vaccine with CASq significantly increases the generation of antigen‐specific antibodies and T cell immune responses in mice, as well as resulting in complete prevention of disease symptoms and protection against lethal infection.
A cationic amphiphilic graft poly(amino acid)‐based oil‐in‐water emulsion adjuvant, containing squalene (CASq) enhanced Ag cellular uptake and improved immune‐stimulation activity of vaccines against the influenza virus, by eliciting both humoral and cellular immunity. CASq is a novel adjuvant for highly specific and powerful immune responses, showing potential in future infectious disease prevention.
Plasmonic Vesicles
In article number 2305748, Daesub Song, Seungjoo Haam, and co‐workers present a plasmonic vesicle (PV)‐mediated fusogenic immunoassay for influenza A virus (IAV) detection. ...Integrating target‐specific capture and IAV‐PV fusion complex formation allows the crucial need to detect intact virions with infectivity, combating the spread of the virus.
The rapid transmission and numerous re‐emerging human influenza virus variants that spread via the respiratory system have led to severe global damage, emphasizing the need for detection tools that ...can recognize active and intact virions with infectivity. Here, this work presents a plasmonic vesicle‐mediated fusogenic immunoassay (PVFIA) comprising gold nanoparticle (GNP) encapsulating fusogenic polymeric vesicles (plasmonic vesicles; PVs) for the label‐free and colorimetric detection of influenza A virus (IAV). The PVFIA combines two sequential assays: a biochip‐based immunoassay for target‐specific capture and a PV‐induced fusion assay for color change upon the IAV–PV fusion complex formation. The PVFIA demonstrates excellent specificity in capturing the target IAV, while the fusion conditions and GNP induce a significant color change, enabling visual detection. The integration of two consecutive assays results in a low detection limit (100.7919 EID50 mL−1) and good reliability (0.9901), indicating sensitivity that is 104.208 times higher than conventional immunoassay. Leveraging the PV viral membrane fusion activity renders the PVFIA promising for point‐of‐care diagnostics through colorimetric detection. The innovative approach addresses the critical need for detecting active and intact virions with infectivity, providing a valuable tool with which to combat the spread of the virus.
This work presents a plasmonic vesicle‐mediated fusogenic immunoassay (PVFIA) for the label‐free and colorimetric detection of influenza A virus (IAV). PVFIA demonstrates excellent specificity in capturing the target, while the fusion assay with gold nanoparticle (GNP) encapsulating fusogenic plasmonic vesicles (PVs) enables visual detection. The results show a low detection limit (100.7919 EID50 mL−1) and good reliability (0.9901), indicating sensitivity 104.208 times higher than conventional immunoassay.
Avian influenza virus (AIV) causes acute infectious diseases in poultry, critically impacting food supply. Highly pathogenic avian influenza viruses (HPAIVs), in particular, cause morbidity and ...mortality, resulting in significant economic losses in the poultry industry. To prevent the spread of HPAIVs, detection at early stages is critical to implement effective countermeasures such as quarantine and isolation. Through a viral fusion mechanism, cell-mimetic nanoparticles (CMPs), developed in the current study, can rapidly detect HPAIV and low pathogenic AIV (LPAIV). The CMPs comprise polymeric nanoparticles, which are constructed using sialic acid and fluorescence resonance energy transfer (FRET) dye pairs that expose the FRET off signal in response to LPAIV and HPAIV, after activation by enzymatic cleavage in the endosomal environment. The CMPs detect a wide variety of LPAIVs and HPAIVs in biological environments. Additionally, the cross-reactivity of CMPs is determined by testing their function with different viral species. Therefore, these findings demonstrate the significant potential of the proposed strategy for mimicking viral infection in vitro and using them as a highly effective diagnostic assay to rapidly detect LPAIV and HPAIV, preventing economic losses associated with viral outbreaks.
Infectious diseases pose persistent threats to public health, demanding advanced vaccine technologies. Nanomaterial-based delivery systems offer promising solutions to enhance immunogenicity while ...minimizing reactogenicity. We introduce a self-assembled vaccine (SAV) platform employing antigen-polymer conjugates designed to facilitate robust immune responses. The SAVs exhibit efficient cellular uptake by dendritic cells (DCs) and macrophages, which are crucial players in the innate immune system. The high-density antigen presentation of this SAV platform enhances the affinity for DCs through multivalent recognition, significantly augmenting humoral immunity. SAV induced high levels of immunoglobulin G (IgG), IgG1, and IgG2a, suggesting that mature DCs efficiently induced B cell activation through multivalent antigen recognition. Universality was confirmed by applying it to respiratory viruses, showcasing its potential as a versatile vaccine platform. Furthermore, we have also demonstrated strong protection against influenza A virus infection with SAV containing hemagglutinin, which is used in influenza A virus subunit vaccines. The efficacy and adaptability of this nanostructured vaccine present potential utility in combating infectious diseases.
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