On January 19, 2022, the research team of Professor Xu Chuanli of Jiangnan University published a research paper entitled "Enantiomer-dependent immunological response to chiral nanoparticles" in nature, revealing the characteristics of unique chiral nanomaterials as immune adjuvants that can uniformly mediate humoral immune responses and cellular immune responses, which not only provides theoretical support for the development of protective vaccines. And it points the way for the development of therapeutic vaccines.
Aluminum adjuvants have been used in the development of human vaccines since 1926. However, aluminum adjuvants can only activate humoral immunity, can not effectively activate the cellular immune response, the effect of antiviral infection is very limited, and the mechanism of action with the human immune system is not yet fully understood. Most of the adjuvants used in clinical practice for a long time have been controlled by foreign pharmaceutical companies, and the vaccine freeze-thaw of its components has led to a significant decline in vaccine activity, so there are extremely high requirements for production, storage and transportation. Therefore, the development of immune adjuvants with independent intellectual property rights is of great significance for the research and development of new, safe and efficient vaccines.
How do chiral adjuvants help vaccine development?
Chirality refers to the property that an object cannot coincide with its mirror image, exists at various scales from micro to macroscopic, and is of great significance to the origin of life and the system of life. There is a chiral preference for the life-chemical reactions carried out in the organism, and the small molecules that construct biological macromolecules such as proteins and nucleic acids also specifically select left-handed amino acids and right-handed sugars.
In this work, the research team developed a strong chiral nanomaterial with an asymmetric factor of 0.44, which was used as an immune adjuvant to effectively sensitize immune cells, so that the expression of cytokines such as tumor necrosis factor - α, γ - interferon, interleukin-12 increased by 1 to 2 times. Through a mouse model infected with H9N2 influenza virus, the researchers demonstrated that left-handed immune adjuvants can effectively promote cellular immune responses and humoral immune responses, and maintain the health and stability of the internal environment. The titer of antibodies produced by left-handed immune adjuvants is more than 800 times that of traditional commercial aluminum adjuvants and more than 1580 times that of right-handed nano-adjuvants.
Mechanism of chiral nanoadjuvant activation of immune response Diagram | Xu came to provide a picture
The study showed that chiral adjuvants specifically bound to molecules such as CD97 and EMR1 of the G protein-coupled receptor family on the surface of antigen-presenting cells, activating the inflammatory body pathway and promoting the effective presentation of antigens. Strong chiral immune adjuvants promote lymphocyte activation, proliferation and differentiation, produce cytokines such as IL-2, IL-4, IL-12, IFN, etc., and induce cellular immune responses and humoral immune responses, thereby better preventing infection and bringing lasting vaccine protection.
What's different about this study?
Chiral regulation of the body's immune response has found a fundamental breakthrough for the future development of new vaccine adjuvants. Professor Xu Laili, the corresponding author of the study, said: "In the past, the research and development of vaccines mainly emphasized the study of candidate antigens or antigen genes, and our research started from the chiral design of immune adjuvants, to some extent, subverting the traditional concept and realizing the source innovation from '0 to 1'. ”
Professor Xu Said: "There has been more experience in the research and development of protective vaccines in the world, but the research and development of therapeutic vaccines, especially anti-tumor vaccines, has not been satisfactory. Our proposed chiral immune adjuvant not only induces humoral immune response, produces antibodies with high titers, but also induces cellular immune responses in a balanced manner, which will provide a new idea for immunotherapy for chronic infections, tumors and other diseases. ”
Professor Xu Chuanlai supervised the doctoral students | Xu came to provide a picture
"In order to remove the influence of chiral molecules during the experiment, we used a non-chiral thiogylation reagent to remove the chiral ligands on the surface of the particles. At the same time, the experimental results were verified by using human dendritic cells, the surface of human dendritic cells mainly expressed CD97 molecules, the affinity between left-handed nano-adjuvants and CD97 was 14 times that of right-handed materials, and its rate of entering cells was 2 times that of right-handed adjuvants. Left-handed nanomaterials enter dendritic cells, produce a variety of cytokines, thereby promoting their uptake and presentation of antigens, while inducing humoral immunity and cellular immune responses, showing the great potential of chiral nanomaterials as immune adjuvants. Xu Liguang, the first author of the paper, said.
Three highlights of this study
· Polarized photosynthesis of strong chiral nanoadjuvants: In the synthesis of strong chiral nanomaterials, researchers screened a series of chiral ligands, introduced polarized light during the preparation of nanoparticles, and optimized combinations with polarized light of different wavelengths to induce symmetry fracture on high-index crystal surfaces, and finally obtained strong chiral nano-adjuvants with uniform surface morphology and anisotropic factors of up to 0.44, realizing the accurate synthesis of mirror-image strong chiral nano-adjuvants.
· Discovered the mechanism by which chiral nanoadjuvants enter immune cells: Through cryo-EM, spectroscopic, and protein analysis, the research team discovered and confirmed that the mechanism of chiral nanoadjuvants entering cells is mediated mainly by two seven-time transmembrane proteins, CD97 and EMR1.
· Discovered the mechanism by which chiral nanoassymembers mediate immune responses: The research team found a correlation between the activation of immune cells and the chiral strength of chiral nanoassynthenics. Chiral nanomaterials mediate cellular immune responses and humoral immune responses by activating the NLRP3 pathway of the inflammasome and regulating cytokine expression patterns.
Thanks
Thank you to Professor Xu Chuanli of the School of Food science of Jiangnan University for his information and suggestions for this article.
Author: Xu Chuanlai Team
Editors: Crispy Fish, Jin Xiaoming
Typography: Chess pieces
Research team
The team of Professor Xu Chuanlai of the National Key Office of Food Science and Technology of Jiangnan University has been committed to the preparation of monoclonal antibodies and the key technologies of immunoanalytic detection of small molecule compounds for more than 30 years. Systematically carried out research on the design and modification of small molecule antigen epitope, proposed the preparation technology of high-titer monoclonal antibody with enhanced matrix effect, and built the largest small molecule monoclonal antibody resource library (more than 5,000 cell lines) at home and abroad; with rapid identification of pollutants and on-site detection as the main line, a series of immune rapid detection test strips, kits, affinity chromatography columns, immunomagnetic beads and rapid detection reagents and instruments were developed, which are widely used in the daily monitoring of risk factors in food, grain, agricultural products, cosmetics, and the environment.
The research team | Xu came to provide a picture
Thesis information
Published the journal Nature
Published January 19, 2022
Publish the title
Enantiomer-dependent immunological response to chiral nanoparticles
(DOI:10.1038/s41586-021-04243-2)