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e. The Oxford–AstraZeneca COVID‑19 vaccine, sold under the brand names Covishield [31] and Vaxzevria [1] [32] among others, is a viral vector vaccine for the prevention of COVID-19. It was developed in the United Kingdom by Oxford University and British-Swedish company AstraZeneca, [33] [34] [35] using as a vector the modified chimpanzee ...
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. [1] [2] The safety and effectiveness of vaccines has been widely studied and verified. [3] [4] A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or ...
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ), the virus that causes coronavirus disease 2019 ( COVID‑19 ). Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing ...
- 新冠肺炎-疫苗資訊最前線
mRNA in vitro transcription, innate and adaptive immunity activation An mRNA vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen (such as a ...
- History
- Applications
- Advantages
- Disadvantages
- Plasmid Vectors
- Delivery
- Dosage
- Immune Response
- Mechanistic Basis For Dna-Raised Immune Responses
- Immune Response Modulation
Conventional vaccines contain either specific antigens from a pathogen, or attenuated viruses which stimulate an immune response in the vaccinated organism. DNA vaccines are members of the genetic vaccines, because they contain a genetic information (DNA or RNA) that codes for the cellular production (protein biosynthesis) of an antigen. DNA vaccin...
As of 2021[update]no DNA vaccines have been approved for human use in the United States. Few experimental trials have evoked a response strong enough to protect against disease and the technique's usefulness remains to be proven in humans. A veterinary DNA vaccine to protect horses from West Nile virus has been approved.Another West Nile virus vacc...
No risk for infectionsAntigen presentation by both MHC class I and class IImoleculesPolarise T-cell response toward type 1 or type 2Immune response focused on the antigen of interestLimited to protein immunogens (not useful for non-protein based antigens such as bacterial polysaccharides)Potential for atypical processing of bacterial and parasite proteinsPotential when using nasal spray administration of plasmid DNA nanoparticles to transfect non-target cells, such as brain cellsCross-contamination when manufacturing different types of live vaccines in same facilityVector design
DNA vaccines elicit the best immune response when high-expression vectors are used. These are plasmids that usually consist of a strong viral promoter to drive the in vivo transcription and translation of the gene (or complementary DNA) of interest. Intron A may sometimes be included to improve mRNA stability and hence increase protein expression. Plasmids also include a strong polyadenylation/transcriptional termination signal, such as bovine growth hormone or rabbit beta-globulin polyadenyl...
Mechanism of plasmids
Once the plasmid inserts itself into the transfected cell nucleus, it codes for a peptide string of a foreign antigen. On its surface the cell displays the foreign antigen with both histocompatibility complex (MHC) classes I and class II molecules. The antigen-presenting cell then travels to the lymph nodes and presents the antigen peptide and costimulatory molecule signalling to T-cell, initiating the immune response.
Vaccine insert design
Immunogens can be targeted to various cellular compartments to improve antibody or cytotoxic T-cell responses. Secreted or plasma membrane-bound antigens are more effective at inducing antibody responses than cytosolic antigens, while cytotoxic T-cell responses can be improved by targeting antigens for cytoplasmic degradation and subsequent entry into the major histocompatibility complex (MHC) class I pathway. This is usually accomplished by the addition of N-terminal ubiquitinsignals. The co...
DNA vaccines have been introduced into animal tissues by multiple methods. In 1999, the two most popular approaches were injection of DNA in saline: by using a standard hypodermic needle, or by using a gene gun delivery.Several other techniques have been documented in the intervening years.
The delivery method determines the dose required to raise an effective immune response. Saline injections require variable amounts of DNA, from 10 μg to 1 mg, whereas gene gun deliveries require 100 to 1000 times less. Generally, 0.2 μg – 20 μg are required, although quantities as low as 16 ng have been reported. These quantities vary by species. M...
Helper T cell responses
DNA immunization can raise multiple TH responses, including lymphoproliferation and the generation of a variety of cytokine profiles. A major advantage of DNA vaccines is the ease with which they can be manipulated to bias the type of T-cell help towards a TH1 or TH2 response. Each type has distinctive patterns of lymphokine and chemokine expression, specific types of immunoglobulins, patterns of lymphocyte trafficking and types of innate immune responses.
Cytotoxic T-cell responses
One of the advantages of DNA vaccines is that they are able to induce cytotoxic T lymphocytes (CTL) without the inherent risk associated with live vaccines. CTL responses can be raised against immunodominant and immunorecessive CTL epitopes, as well as subdominant CTL epitopes,[jargon] in a manner that appears to mimic natural infection. This may prove to be a useful tool in assessing CTL epitopes and their role in providing immunity. Cytotoxic T-cells recognise small peptides (8-10 amino aci...
Humoral (antibody) response
Antibody responses elicited by DNA vaccinations are influenced by multiple variables, including antigen type; antigen location (i.e. intracellular vs. secreted); number, frequency and immunization dose; site and method of antigen delivery.
DNA uptake mechanism
When DNA uptake and subsequent expression was first demonstrated in vivo in muscle cells, these cells were thought to be unique because of their extensive network of T-tubules. Using electron microscopy, it was proposed that DNA uptake was facilitated by caveolae (or, non-clathrin coated pits). However, subsequent research revealed that other cells (such as keratinocytes, fibroblasts and epithelial Langerhans cells) could also internalize DNA.The mechanism of DNA uptake is not known. Two theo...
Antigen presentation by bone marrow-derived cells
Studies using chimeric mice have shown that antigen is presented by bone-marrow derived cells, which include dendritic cells, macrophages and specialised B-cells called professional antigen presenting cells (APC). After gene gun inoculation to the skin, transfected Langerhans cells migrate to the draining lymph node to present antigens. After IM and ID injections, dendritic cells present antigen in the draining lymph nodeand transfected macrophages have been found in the peripheral blood. Bes...
Target site role
IM and ID DNA delivery initiate immune responses differently. In the skin, keratinocytes, fibroblasts and Langerhans cells take up and express antigens and are responsible for inducing a primary antibody response. Transfected Langerhans cells migrate out of the skin (within 12 hours) to the draining lymph node where they prime secondary B- and T-cell responses. In skeletal muscle, striated muscle cells are most frequently transfected, but seem to be unimportant in immune response. Instead, IM...
Cytokine modulation
An effective vaccine must induce an appropriate immune response for a given pathogen. DNA vaccines can polarise T-cell help towards TH1 or TH2 profiles and generate CTL and/or antibody when required. This can be accomplished by modifications to the form of antigen expressed (i.e. intracellular vs. secreted), the method and route of delivery or the dose. It can also be accomplished by the co-administration of plasmid DNA encoding immune regulatory molecules, i.e. cytokines, lymphokines or co-s...
Immunostimulatory CpG motifs
Plasmid DNA itself appears to have an adjuvant effect on the immune system. Bacterially derived DNA can trigger innate immune defence mechanisms, the activation of dendritic cells and the production of TH1 cytokines. This is due to recognition of certain CpG dinucleotide sequences that are immunostimulatory. CpG stimulatory (CpG-S) sequences occur twenty times more frequently in bacterially-derived DNA than in eukaryotes. This is because eukaryotes exhibit "CpG suppression" – i.e. CpG dinucle...
Alternative boosts
DNA-primed immune responses can be boosted by the administration of recombinant protein or recombinant poxviruses. "Prime-boost" strategies with recombinant protein have successfully increased both neutralising antibody titre, and antibody avidity and persistence, for weak immunogens, such as HIV-1 envelope protein.Recombinant virus boosts have been shown to be very efficient at boosting DNA-primed CTL responses. Priming with DNA focuses the immune response on the required immunogen, while bo...
Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating the body's adaptive immunity, they help prevent sickness from an infectious disease. When a sufficiently ...
COVID-19 vaccine vial prop A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.
