A novel virus-to-vaccine strategy: building a virus-entrapped hydrogel micro-factory

Scientists developed a novel vaccine technology by direct trapping a live virus within an immune modulating hydrogel without any prior treatment. Creating an immune active microenvironment, the hydrogel-based niche enables viruses' removal and processing to induce effective immune protection.
A novel virus-to-vaccine strategy: building a virus-entrapped hydrogel micro-factory
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Vaccines are one of the most powerful means for humans to deal with large-scale epidemics of infectious diseases. However, vaccine development is a complex endeavor and still lags behind the emerging virus. The threat of new viral outbreaks has heightened the need for ready-to-use vaccines that are safe and effective. Professor Tang, Ruikang of the Department of Chemistry of Zhejiang University, Wang, Xiaoyu, associate researcher of Qiushi Academy for Advanced Studies, and Prof. Hou, Lihua of Beijing Institute of Microbiology and Epidemiology, proposed a novel vaccine technology with reliable safety and effectiveness. They "tie up" wild virus to hydrogel scaffold to confine virus and form an immune "micro-factory" for virus clearance and processing, leading to effective immune protection.

They loaded wild-type Zika virus (ZIKV) directly into a chitosan gel and named the "plug and play" type composite gel as Vax. The composite hydrogel contains chitosan hydrogel as a virus trapper and built-in adjuvant, and calcium carbonate nanoparticles (nano-CaCO3) as a hydrogel stabilizer and Ca2+ source. The safety of VAX is ensured by two lines of defense. The positively charged chitosan hydrogel can firmly adsorb live virus, which is the first line of defense. As second line of defense, the self-adjuvanting chitosan scaffold enables the recruitment of immune cells and the activation of innate immune responses by the upregulation of pattern recognition receptors (PRRs), leading to the generation of immune microenvironment for virus elimination and viral antigen processing. Upon injection with ZIKV-loaded chitosan hydrogel, major organs of vaccinated mice showed no trace of virus. After 28 days, the ZIKV RNA inside Vax was also undetectable. Moreover, the Vax showed beneficial effect on antigen presentation in lymph nodes due to the expanded germinal center (GC) B cells and improved cross-presentation.

In animal experiments, a single-dose vaccination of ZIKV-loaded Vax evoked robust antigen-specific adaptive responses and immune memory, which protected mice against lethal infection.  Related paper, Immunization against Zika by entrapping live virus in a subcutaneous self-adjuvanting hydrogel, was published in the journal Nature Biomedical Engineering. Vax means that with the virus, there is a vaccine. It demonstrates the feasibility of directly converting viruses into vaccines through a material-based tactic.

In 2020, a commentary on Science wrote that next-generation vaccine technologies should focus on rapidly transforming wild virus strains into vaccines with high safety and efficacy. The solution proposed by Ruikang Tang 's team shows a good prospect of directly converting viruses into vaccines by prisoning live viruses into a designed immune-modulating hydrogel. "As soon as we get a purified virus, we can mass-produce vaccines. This can shorten the development process of vaccines.” Tang hopes that Vax will become a universal vaccine developing technology, and if there is a new virus that threatens humans, Vax is expected to respond quickly.

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