mRNA Vaccine

Creative BioLabs is a contract research organization based in New York. They specialize in antibody discovery, engineering, and biomanufacturing. They also offer mRNA vaccine technology. mRNA, or messenger RNA, is a molecule responsible for transferring genetic information from DNA to protein. mRNA vaccines deliver mRNA that encodes the antigen protein of a pathogen to cells, stimulating an immune response. mRNA vaccines have advantages like shorter development and production cycles compared to traditional vaccines. There are two types of mRNA vaccines: non-replicating mRNA and self-amplifying mRNA. Delivery methods include viral and non-viral carriers, with liposomes being the most effective. mRNA vaccines can also be delivered without carriers in a naked format. Dendritic cells are often used for mRNA vaccine administration. The administration route is important for the metabolism and translation efficiency of mRNA vaccines. Creative BioLabs has multiple mRNA platforms for vaccine de Welcome to Creative BioLabs. 100% of the effort, 100% of the service. As a dynamic contract research organization, we are based in New York and serve the whole world. Our seasoned scientists are skilled in antibody discovery, antibody engineering, and biomanufacturing solutions. Hi everybody. Today, we are going to introduce you to mRNA vaccine. We will discuss what is mRNA and mRNA vaccine, characteristic of mRNA vaccine, mechanism of action of mRNA-based vaccines, types of mRNA vaccine, delivery strategies of mRNA vaccine, administration routes for mRNA vaccines and mRNA vaccine platforms of Creative BioLabs. mRNA, also called messenger RNA, is a single-stranded RNA molecule produced during transcription. It is responsible for transferring genetic information from DNA to protein. Thus, it can also be considered as a template for protein translation. mRNA vaccine is a novel vaccine technology, which delivers mRNA that encoding the antigen protein of pathogen to the cell, and expresses the antigen protein, and then stimulates the immune response of the body. Compared with the first and second generation vaccines, mRNA vaccine has the advantages of short development cycle of 3 to 5 years, relative safety, long immune response time, short production cycle, usually 40 days. Similar to DNA vaccine, mRNA vaccine expresses intracellular antigen, while overcomes the shortcomings of low immunogenicity, and nonspecific immunity against vector, and has no risk of integrating into host DNA. Based on the inherent mechanism of mRNA transcription and translation in cells, we only need to focus on the mRNA fragments that we designed, which greatly reduces the complexity of vaccine production. Therefore, the research and development cycle of mRNA vaccine is much less than that of traditional vaccines, which can save a lot of RD costs for researchers. mRNA is transported to antigen-presenting cell, and translated into target antigen by ribosome. Then the antigen is degraded by proteasome to form polypeptide epitope. Which binds to MHC molecule of major histocompatibility complex, in endoplasmic reticulum. The MHC complex is presented on the surface of APC, and activate antigen-specific T and B cells, to elicit immune response. There are two processed pathways for synthetic antigens, one is decomposed into peptides by host proteasomes, which are accepted by major histocompatibility complex class 1, and delivered to the cell surface, to induce CDAT cellular immune response. Another antigen is then degraded by endosomal proteases into peptides, which are bound by major histocompatibility class 2, then travel to the cell membrane, inducing T cell immune response. At present, there are two mRNAs that can be used to make vaccines, the non-replicating mRNA, and self-amplifying mRNA. The antigens encoded by non-replicating mRNA contain 5 and 3 UTR, while self-amplified RNA can encode not only antigens, but also sequences similar to viral replication process, so that they can replicate in self and increase protein expression. Non-replicative mRNA is synthesized by in vitro transcription, which is consistent with the molecular structure of eukaryotic mRNA, and is mainly composed of 5 UTR, open reading frame, 3 UTR, 5-CAP, and 100-250 BP-Poly-A. Regulatory elements in 5 UTR and 3 UTR stabilize mRNA, and increase antigen-protein translation. Open reading frame is a nucleic acid sequence that encodes antigens, and CAP enables mRNA to translate in the right direction. Poly-A can increase the stability of mRNA and the expression of antigen-protein, playing an important role in the translation and stability of mRNA. The synthesis of mRNA is generally based on the plasmid, containing the target protein open reading frame as a template, transcribed and synthesized in vitro, followed by the addition of 5-CAP and 3-terminal Poly-A. After entering the cells, the mRNA is translated on the ribosome to form functional proteins. Virus-derived self-amplifying mRNA is to insert the nucleic acid sequence encoding antigen directly, into single-stranded RNA virus, such as sem-leaky forest virus, yellow fever virus. It usually has high relative molecular weight, and can express a large number of antigens. At present, most of the self-amplifying mRNA vaccines are based on the alpha virus genome, in which the genes encoding mRNA replication mechanism are intact, but the genes encoding structural proteins are replaced by the target genes. Researchers have studied a variety of in-vivo delivery methods of mRNA. We focus on the technologies for delivering mRNA vaccines in carrier-mediated, naked, and DC-based forms. mRNA vaccine delivery carriers mainly include viral carriers and non-viral carriers. Although viral carriers based on lentivirus, adeno-associated virus and sendivirus, can deliver nucleic acid, they may be limited by the immune response caused by the carriers, and the potential application could be affected. Non-viral carriers mainly include liposomes, dendritic cell, inorganic nanoparticles, cationic cell membrane-penetrating peptides and so on. Among them, liposome delivery mRNA has unique advantages. 1. Liposomes are spherical vesicles, which can encapsulate mRNA to resist the action of nuclease. 2. Liposomes are similar to cell membrane and are easy to fuse with recipient cells, and the transfection efficiency is high. 3. Liposomes can deliver different sizes of mRNA. 4. Liposomes as delivery carriers are not restricted by the host. Up until now, lipid vectors have become the most effective non-viral carriers for delivering mRNA. mRNA vaccines can be delivered without any additional carriers, that is, in a naked format. mRNA is dissolved in buffer, and then injected directly. At present, the detailed mechanism of naked mRNA transmission is not clear. One idea proposed that naked mRNA is internalized by macropinocytosis. This macropinocytosis pathway is highly active in macrophages and immature dendritic cells, which play an important role in the development of immune response. Another possible mechanism is that the cellular uptake of naked mRNA via mechanical forces. One possible force is the hydrostatic pressure, formed after fast injection of a relatively large volume into small mammals. This pressure may disrupt the cell membrane, and permit cytosolic delivery of nucleic acids. However, the specific mechanism still needs to be proved by more research. Naked mRNA has two advantages. 1. Easy to store and prepare. In the presence of storage reagents, such as 10% trehalose, freeze-dried naked RNA can be stable for up to 10 months at 4C. Before administration, the naked mRNA vaccine only needs to be dissolved in the buffer. 2. Vaccines made from unmodified nucleotides have dual advantages in innate immunogenicity. Immunogenicity may be beneficial to vaccination by providing some adjuvant activity. On the other hand, the activation of some RNA sensors may inhibit mRNA translation in the cytoplasm. As the most effective APC, dendritic cell can present antigens processed from various sources. Some special characteristics of dendritic cell make it a suitable vaccination target, including the directional migration of dendritic cell and lymph nodes, and the high expression of major histocompatibility complex molecules, custimulators, and cytokines. Autologous dendritic cell from primary human PBMC is the main source for the preparation of mRNA-treated dendritic cell for in vivo applications. The main strategies for the transmission of mRNA to dendritic cell are electroporation and lipid-derived carriers. Dendritic cells-based mRNA vaccines have two advantages. 1. Effective APC is essential for innate, adaptive immunity. 2. Biocompatibility. The administration route for mRNA vaccine is very important, which will determine the metabolism of mRNA vaccine in vivo, and the translation efficiency of target antigen protein. For example, if untreated naked mRNA is injected directly intravenously, it will be rapidly degraded by nucleuses in the blood. In addition, the expression position of antigen protein also determines the choice of drug administration route. The main injection routes include intradermal injection, subcutaneous injection, intramuscular injection, nodule injection, and intravenous injection. Intradermal injection can deliver mRNA vaccine directly into the dermis and make it extracted by APC cells, but the disadvantage is that it has local side effects, and the injection volume is limited. Subcutaneous injection can have a larger injection volume and reduce local adverse reactions. However, the absorption rate of SC region is very slow, which may lead to accidental degradation of mRNA vaccine. Muscles contain a large network of blood vessels that help recruit different types of immune cells, such as infiltrating APC, and recycle them to the injection site. The local reaction of intramuscular injection is mild, but the injection volume is limited. Intranodal injection directly makes the APC in the lymphoid organs and can easily phagocytize the injected mRNA vaccine, which improves the efficacy of the vaccine, but the vaccination procedure is complicated. The injection volume of intravenous injection is large, so that mRNA can enter APC and lymphoid organs directly. However, there is a risk of systemic side effects due to the degradation of mRNA. Creative Biolabs is a professional manufacturer of vaccines, and has built multiple mRNA platforms based on 10 years of exploration. Our mRNA platforms include non-replicating mRNA vaccine platform, mRNA vaccine platform, mRNA pharmacology optimization platform, and self-amplifying mRNA vaccine platform. We have an integrated research and development system, and a complete and separate service system. We can provide you with strategies for vaccine development and help you evaluate and optimize the immunogenicity of your vaccine, as well as any other products and services related to vaccine research. You can contact us if you have any questions about vaccines, and we will provide the most appropriate solution according to your needs.