Create a Vaccine Using a Live Virus!

On March 23, Professor Tang Ruikang from the Department of Chemistry of Zhejiang University, Associate Researcher Wang Xiaoyu from Qiushi Institute of Advanced Studies, and Researcher Hou Lihua from the Institute of Biological Engineering, Institute of Military Medical Research, Academy of Military Sciences, published a research paper in Nature Biomedical Engineering, proposing a new vaccine technology—encapsulating wildlife viruses directly into gel materials, forming immune "microfactories" at targeted locations in the body, locking up viruses while safely and efficiently activating immune responses and forming immune memories. Recent and emerging outbreaks of viral infections caused by Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus continue to pose a significant global public health challenge. Often, whole virus vaccine strategies (e.g., attenuated or inactivated) can be used to convert virulent viruses directly into vaccines. However, their widespread usage has been hampered by the whole virus vaccines' lower immunity, safety concerns, and time-consuming production methods. There is a strong impetus to create cutting-edge vaccination technologies that can swiftly transform viral strains from the wild into safe and effective vaccines. The creation of next-generation viral vaccines may benefit from nanotechnology's capacity to regulate antigen loading, distribution, and release, hence increasing the efficacy and durability of the immune response. But off-target dispersion, systemic administration, and limited regulatory effects mean that spatial and temporal control remains an unsolved hurdle for nanoparticle engineering. An interesting alternative to vaccine engineering is the manipulation of the immune microenvironment where the virus resides, thus enabling spatial and temporal manipulation of the interactions between the virus and immune cells. In this regard, 3D macroscopic scaffolds that can recruit antigen and chemokine loading of cells at the injection site are recommended due to their in situ immunomodulatory properties. However, the key challenge in converting viruses into vaccines using material scaffolds is to limit viral infection while enhancing local innate responses, which can locally aggregate immune cells at the injection site, trigger antiviral responses, and process viral antigens. However, due to the absence of spatiotemporal regulation of innate immunity, macroscale scaffolds with prior loading and release effects do not satisfy the design criteria for viral vaccines. The development of a strong innate immune response is crucial for virus clearance and subsequent adaptive immune response because it is the host's first line of defense against viral infection. Therefore, the capability to capture the virus while restricting its dissemination is essential to the new strategy. The timing and location of viral processing can be regulated by recruiting and modulating immune cells at the injection site. Using chitosan oligomer hydrogel as a virus-trapping agent, a built-in adjuvant, and calcium carbonate nanoparticles (nano-CaCO3) as a stabilizer and Ca2+ source, the authors created a virus-trapping hydrogel known as Vax. Chitosan scaffolds' self-adjuvant characteristics promote innate immune responses and cell recruitment by activating pattern recognition receptors, and their positively charged side chains trap viruses efficiently through electrostatic interactions. (PRRs). Because of this, hydrogels create inflammatory ecotopes for viral uptake and antigen processing, which benefits antigen presentation in lymph nodes. Increased humoral and cellular immunity is the result of the maturation of germinal center (GC) B cells and enhanced cross-presentation. Therefore, a potential method for the prevention of developing infectious diseases is single-dose immunization made by loading live pathogenic ZIKV onto scaffolds without previous treatment, which can elicit effective immunity and protect mice against lethal infections. Studies have shown that a subcutaneous vaccine consisting of live Zika virus electrostatically captured in a self-adjuvant hydrogel recruits immune cells at the injection site and provides mice with effective protection against a lethal viral attack. Resource: https://www.creative-biolabs.com/vaccine/target-zika-virus-9.htm