Following the release of the genetic strain of the SARS-CoV-2 virus in January 2020, pharmaceutical companies around the world have been racing to develop a safe and effective vaccine, with many reaching clinical trials in higher time.
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In comparison, 22 months had elapsed after the start of MERS-CoV in 2012 before an approved vaccine was available. The mode of action and members of a particular vaccine can change wildly, just as the viruses protect against different cells and take different pathways to infection.
SARS-CoV-2 has been reported to induce a range of immune responses in patients, with some non-specific and others equally hospitalized, and this variability improves a long – lasting vaccine guarantees immunity throughout the host population.
SARS-CoV-2 binds to the angiotensin-converting enzyme receptor 2 (ACE2) receptor, which is expressed in many tissues and organs throughout the body, especially in the lungs, the gut, and the brain. The widespread manifestation of the ACE2 receptor is partly due to the COVID-19 variable signals.
T-cells are dependent on immune memory and the generation of high-affinity antibodies, and patients with SARS-CoV-2 infection tend to show high levels of antibody for significant periods after infection.
Unlike most other inactivated vaccines (made up of virus grains that have no disease-producing ability) or weakness (made less harmful or brutal), many of the vaccines are approved for use against COVID-19 to date based on nanotechnology.
mRNA vaccines
Two of the earliest companies to name a successful vaccine were Moderna and Pfizer-BioNTech, both of which use lipid nanoparticles to capture mRNA-paying weight. The mRNA encodes for the production of an antigen specifically known for SARS-CoV-2, allowing the cell’s machinery to produce the antigen and then the body develops immunity.
The use of nanoparticle lipid transport can provide several benefits, including the ability of direct cytoplasmic delivery and increased specificity towards antigen-expressing cells. Full details of each form have not been released, although Pfizer-BioNTech lipid nanoparticle is known to be slightly cationic, which may be helpful in cell injection due to the small negative size of the cell membrane .
Both Moderna and Pfizer-BioNTech vaccines use mRNA encoding for the SARS-CoV-2 spike protein, the protein that would bind to the ACE2 receptor. The spike protein has two subunits, the first of which is responsible for the first binding with ACE2 while the second stimulates viral fusion.
The Moderna vaccine, mRNA-1273, encodes specifically for the pre-fusion form of the protein and is virtually complete in addition to two amino acid substitutions at 986 and 987 positions that help maintain the stable protein in this pre-fusion state. The surrounding lipid nanoparticle is made up of four lipids, the exact structure of which remains to be elucidated. However, lipid-nanoparticle-based vaccines from Moderna contain 1,2-distearoyl-.sn-glycero-3-phosphocholine, cholesterol, and polyethylene glycol-lipid, which may be true here as well.
The mRNA used by the Pfizer-BioNTech vaccine (BNT162) encodes only the spike protein receptor binding domain, which is found on the first subunit of the protein. The mRNA was modified to include 1-methylpseudouridine, which helps to reduce the immunogenicity of the mRNA and increase the rate of translation, most likely through improved stability of the molecule, although this has not been fully explained. still.
Again, the exact form of the lipid nanoparticle transporter has not been revealed, although old papers from the company show that it may contain phosphatidylcholine, cholesterol, and polyethylene glycol-lipid.
The vaccine technology used by these companies has not yet been approved after initial clinical trials for any other disease, but in this case the development time is very fast and the urgency of the situation has affected this technology. bring to light.
Because the vaccine itself does not carry the antigen there is little chance of serum neutralization, and booster regimens are less contraindicated. Because RNA reproduces in the cytoplasm it does not need to be localized to the nucleus, like DNA. However, DNA vaccines generally offer a longer duration of reproduction and are less likely to require further enhancement. As a result of this, several other companies have been working towards DNA-based vector vaccination.
Viral vector vaccines
Adenoviruses are simple, unbranched viruses containing a two-stranded sequential DNA genome, and are responsible for a number of diseases including the common cold. Adenovirus vectors are used in vaccines to secrete foreign antigens and thus stimulate an immune response, accomplished by replacing the adenovirus with sections of DNA.
Adenoviral DNA does not weave into the host genome, and is not reproduced during cell division. Because the adenovirus comes from a family of common viruses including the common cold, many patients have already developed neutral antibodies, leading to the use of adenoviruses that had originally grown to other species. captured, and to which people have no immunity.
The Oxford-AstraZeneca (ChAdOx1) vaccine uses adenovirus vector derived from the chimpanzee, incorporating genetic sequences that mimic cell machinery to produce full-length spike proteins SARS-CoV-2. Some modifications were made to the genetic sequence that inhibited the reproduction and promotion of translation, in particular by the elimination of E1 and E3 and the introduction of the plasminogen activator conductor sequence clo.
The Chinese vaccine company CanSino took a similar approach, although they used a native adenovirus for people who are often employed as a vaccine vector: adenovirus type 5. The company noted that about half of the their early participants on immunity to type 5 adenovirus, compared with just 1 in 98 patients for the chimpanzee vaccine received from Oxford-AstraZeneca.
Both vaccines showed some side effects in early clinical trials, including moderate to severe pain, fatigue, and headache, with the Oxford-AstraZeneca vaccine co-administered with anti-inflammatory drug acetaminophen as a warning that seemed to alleviate these problems.
Efficiency and other options
Dozens of additional companies are working towards creating a safe and reliable vaccine, some using the technologies described above, while others rely on more inactive viral vaccine platforms classic. However, the latter are rarely suitable for use by immunocompromised individuals, making it less than ideal for the protection of the most vulnerable.
All three of the vaccines discussed in detail here, BNT162 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (Oxford-AstraZeneca), have been found to have an adequate safety profile over on phase I, II, and III clinical trials, now administered to thousands of patients from around the world. They all report a high level of efficacy, which has been reported as high as 95% by age group, sex, ethnicity, infection status, and dosing schedule.
References
Chung, YH, Beiss, V., Fiering, SN & Steinmetz, NF (2020) COVID-19 vaccine initiators and their nanotechnology design. ACS Nano, 14 (10). https://pubs.acs.org/doi/full/10.1021/acsnano.0c07197
Department of Health and Social Care (DHSC) Pfizer Limited & BioNTech Manufacturing GmbH (2020) Public Assessment Authorization Authorization for Temporary Supply of COVID-19 mRNA Vaccine BNT162b2 (BNT162b2 RNA) aspiring solution for injection. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/944544/COVID-19_mRNA_Vaccine_BNT162b2__UKPAR___PFIZER_BIONTECH__15Dec2020.pdf
Modifications of Li, Z. & Xu, X. (2019) Post-Translation of the Mini-Chromosome Preservation Proteins in DNA Reproduction. Genes, 10 (5). https://www.mdpi.com/2073-4425/10/5/331/htm
Voysey, M. et al. (2021) Safety and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2: an interim study of four randomized controlled trials in Brazil, South Africa, and the UK. The Lancet, 397 (10269). https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltex