Biological Sciences
mRNA Vaccine
mRNA vaccines are a type of vaccine that uses a small piece of genetic material from the virus to instruct cells in the body to produce a harmless piece of the virus, which then triggers an immune response. This approach allows for a faster and more flexible vaccine development process, as the genetic sequence of the virus can be quickly identified and used to create the vaccine.
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4 Key excerpts on "mRNA Vaccine"
eBook - ePubmRNA Therapeutics
Fast-to-Market Strategies
- Sarfaraz K. Niazi(Author)
- 2022(Publication Date)
- CRC Press(Publisher)
- The manufacturing process of mRNA is cell-free and independent of the mRNA sequence, making it easy and fast to develop and mass-produce a new vaccine. Therefore, mRNA Vaccines may be considered a platform technology, which makes them particularly advantageous for tackling pandemics. In contrast, to produce an inactivated or recombinant protein vaccine, it is necessary to develop specific microbial/cell culture processes with particular microbial strains or cell lines that usually require a series of long culture steps to generate the product as custom product recovery and purification steps. Moreover, cell-free manufacturing has a lower risk of microbial contamination.
- Since the antigenic protein is synthesized from the mRNA in the host cell by the host’s cell machinery, the protein generated has precisely the same structural characteristics (including posttranslational modifications) that the actual pathogen’s protein would have in the host. However, when the antigenic protein is produced industrially, for example, using bacteria or yeast cells, this is not always the case.
- In contrast to DNA vaccinations, mRNA does not require entry into the cell nucleus to be decoded, reducing the risk of DNA integration into the genome, which may exist for DNA vaccines.
mRNA does present, however, certain challenges for its use in vaccines:- Cells’ uptake of naked mRNA (i.e., mRNA that is not associated with some sort of delivery carrier such as lipid nanoparticles) is very low under normal circumstances.
- Naked mRNA is highly unstable in vivo, being rapidly degraded by ribonucleases.
- The organism perceives exogenous naked mRNA as antigenic itself and may elicit a strong immune reaction. Although this may be useful for vaccination to a certain extent, it may reduce the translation efficiency of mRNA and consequently hinder the development of an effective immune response against the antigenic protein.
4.6 Nucleoside Vaccines Perspective
It is now conceivable to develop a universal flu vaccine that will protect against every viral strain without being altered every year. Since RNA vaccines can incorporate instructions for several antigens, either strung together in a single strand or packaged together in a single nanoparticle, essentially, a single vaccine in place of multiple sexually transmitted diseases including HPV, HIV, and chlamydia can be combined.
eBook - PDF- ShivSanjeevi Sripathi, Shivsanjeevi Sripathi(Authors)
- 2023(Publication Date)
- Delve Publishing(Publisher)
These vaccine candidates also have the potential for low-cost manufacturing and safer administration. Therefore, mRNA Vaccines have revolutionized the vaccinology field by addressing all of the current challenges (5, 6). The mRNA Vaccine development approach is developing quickly (Figure 1). Significant research investment in this field has allowed mRNA to become a potential candidate in the immunization landscape. Several major technological innovations have been developed in this area, and pre-clinical research data have been developed and accumulated during the last several years (5, 7). The first successful experiment was published in 1990. In this research, Wolff et al. successfully injected mRNA reporter genes into mouse skeletal muscle cells, and protein production was observed, documenting the first attempt at mRNA in vivo expression. This experiment demonstrated a successful method for mRNA Vaccine development (8). Subsequently, several studies were performed on mRNA-based therapeutic development (Figure 2). Vasopressin mRNA was injected into a rat model to understand the uptake, transport, and expression of this mRNA (9). Several other significant innovations were performed that addressed problems in mRNA Vaccine development. One of the important milestones was the assimilation of pseudouridine into mRNA, which provides biological stability and increased translational capacity (10). Another important discovery was optimizing the mRNA coding sequences. In this work, Thess et al. performed sequence engineering of erythropoietin (EPO) mRNA (11). However, codon optimization is not required for mammalian viruses and tumour antigens. Vaccines: What’s Happening 244 Figure 1: The number of publications in PubMed in the mRNA Vaccine area from 2018 to 2020. The PubMed search was performed using the “mRNA vac- cine” keyword on 10 th Jan 2021. Figure 2: Timeline of the research breakthrough and progression of mRNA Vaccine.
- Loutfy H. Madkour(Author)
- 2019(Publication Date)
- Academic Press(Publisher)
20 ]. Nanoparticles have been extensively studied in the field of drug delivery in light of their ability to efficiently deliver drugs to target sites, protect drugs from endogenous enzymes, and remain in the circulation for long periods of time.Cancer immunotherapy is quickly growing to be the fourth most important cancer therapy, after surgery, radiation therapy, and chemotherapy. Immunotherapy is the most promising cancer management strategy because it orchestrates the body’s own immune system to target and eradicate cancer cells, which may result in durable antitumor responses and reduce metastasis and recurrence more than traditional treatments.RNA vaccines traditionally consist of messenger RNA (mRNA) synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen-presenting cells (APCs) to stimulate an immune response. Alternatively, dendritic cells (DCs) can be loaded with either tumor-associated antigen (TAA) mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. Nanomaterials hold great promise in further improving the efficiency of cancer immunotherapy—in many cases, they are even necessary for effective delivery.mRNAs are another kind of nontoxic molecule for nucleic acid-based vaccination therapies. The physiological role of mRNA is to transfer genetic information from the nucleus to the cytoplasm, and then to be translated into its corresponding protein. The safety of mRNA-based treatments supports the use of mRNA vaccination for therapeutic or prophylactic approaches. Due to the ease of degradation of RNA by extracellular ribonucleases the success of RNA vaccines highly depends on a proper delivery system. Based on an established method for liposome-nucleic acid complex (lipoplex, LPX) preparation [21] , an mRNA lipoplex was constructed by mixing the reporter firefly luciferase (Luc)-encoding mRNA and cationic liposomes composed of common lipids such as N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA) and dioleoyl phosphatidylethanolamine (DOPE). By gradually decreasing the positive-to-negative charge ratio, IV-injected Luc-LPX resulted in a luciferase expression shift from the lungs to the spleen, and even an exclusively splenic signal for near-neutral and slightly negative particles. The LPX can protect RNA from degradation by extracellular ribonucleases and can mediate its efficient uptake, as well as facilitating expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments [22]
eBook - PDF- Alain Rolland(Author)
- 1999(Publication Date)
- CRC Press(Publisher)
In theory, the encoding sequences can also be in the form of either DNA or mRNA, however in practice most are made of plasmid DNA and there are only a few examples of RNA vaccines (e.g., Conry et al., 1995; Martinon et al., 1993), probably because expression is too short-lived to be effective. As such, gene- based vaccines are most often referred to as DNA vaccines and the process as DNA-based vaccination or immunization. Other terms applied to this technology include genetic immunization and nucleic acid-based immunization. Disease-specific DNA-based immunization has now been demonstrated in animal models against several viral, bacterial and parasitic diseases. While classical vaccines, which contain some form of the antigen itself, have proven highly effective against many diseases, they still have certain disadvantages and there remain numerous diseases for which it has not been possible to produce effective antigen-based vaccines (Lanzavecchia, 1993; WHO, 1990). DNA vaccines promise to overcome many of the limitations of antigen vaccines. OVERVIEW OF IMMUNE RESPONSES TO VACCINES Two general types of immunity may be induced in response to an antigen, namely humoral immunity and cell-mediated immunity (CMI). These result in the production of antigen-specific antibodies and cytotoxic T-lymphocytes (CTL) respectively (see Kuby, 1994). Humoral immunity involves B cells, which recognize and bind circulating soluble antigen via surface antibody receptors and then respond by producing and secreting antigen-specific antibodies. This process alone results in secretion of T-independent antibody isotypes (IgM and IgG3). However, for induction of the longer-lasting high affinity T-dependent antibodies (e.g., IgG1, IgG2a), B cells must be further stimulated by cytokines secreted from activated T-helper (Th) cells (see below). Some activated B cells become plasma cells that provide long-term memory.
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