Recently, the journal Nature Biomedical Engineering published a research paper titled “Dendritic-cell-targeting virus-like particles as latent mRNA vaccine carriers” about a new vaccine platform technology that can specifically target dendritic cells (DCs) and efficiently deliver mRNA and protein—DC-targeted viroid vector (DVLP).
This brand-new vaccine technology can not only carry mRNA but also display the three-dimensional structure of antigenic proteins on the surface of vaccine particles. It has the ability to effectively activate humoral immunity and cellular immunity and can significantly prevent SARS-CoV-2 infections. In the simple situation that is regarded as a black hole in vaccine development, herpes virus prevention has also played a significant role, bringing potential treatment and prevention methods to hundreds of millions of HSV-infected people around the world. DVLP vaccine technology is expected to become a new vaccine platform and play an important role in the treatment and prevention of viral infections, tumors, and aging.
First, the research team conducted a proof-of-concept study on a virus-like vector vaccine. The research team designed multiple MS2 stem-loops on the target mRNA, allowing them to use the interaction between the MS2 stem-loop structure and the MS2 coat protein to simultaneously load the lentiviral GagPol protein into a virus-like vector, becoming part of its structure. During this process, antigens, which are membrane proteins, will be loaded together and displayed on the surface of DVLP. The researchers verified the successful implementation of this vaccine design idea through various technical means such as electron microscopy, Western blot, and confocal laser imaging.
On this basis, the research team carried out the design and verification of virus-like vectors with dendritic cell targeting. DC is the most important antigen-presenting cell and plays a key role in the effectiveness of vaccines. Currently, PROVENGE, the only approved tumor vaccine in the world, is a DC vaccine. However, PROVENGE production is similar to CAR-T cell therapy. The process is complex and cumbersome, involving the isolation of the patient’s own cells, preparation in vitro, and then infusion into the body. Therefore, it is necessary to develop vaccine technology that can target DCs in vivo, reduce the production success and price of DC vaccines, and improve patient accessibility.
Therefore, the research team first engineered the Sindbis virus glycoprotein SV-G and replaced the broad-spectrum affinity glycoprotein VSV-G to achieve specific targeting of DCs by virus-like vectors by recognizing the DC surface protein DC-SIGN. By tracking the infection of dendritic cell lines in vitro and the infection of DCs in vivo, the research team verified that the SV-G modified virus-like vector indeed obtained the targeting ability of DCs. The research team named this virus-like vector vaccine technology with DC-targeting DVLP. By detecting the distribution of mRNA in the body, the research team found that, compared with LNP, DVLP can efficiently deliver antigen mRNA into DCs, and DCs can migrate to lymph nodes more effectively. DVLP also activated cellular immunity more effectively than the LNP mRNA vaccine.
Finally, the research team used two viral infections, SARS-CoV-2 and HSV-1, as disease models to evaluate the protective effect of the DVLP vaccine on mice. In the SARS-CoV-2 real virus infection experiment, the research team found that mice immunized with DVLP Spike had significantly reduced viral loads in the lungs and trachea, and at the same time attenuated the pulmonary inflammatory response. In the HSV-1 skin infection model, the research team found that mice immunized with DVLP gB1-gD1 produced neutralizing antibodies that cross-protected HSV-1 and HSV-2. The viral load was significantly reduced, effectively preventing HSV infection from damaging the skin of mice.
In summary, this study developed a new vaccine technology, DVLP, that can target DCs in vivo, deliver mRNA and display antigenic proteins at the same time, and stimulate strong humoral and cellular immune responses. Therefore, DVLP is expected to become a new generation of vaccine technology to fight viral infections, prevent and treat tumors, and treat aging. At present, preparatory work has also been launched for anti-tumor clinical research based on this vaccine technology.
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