The Covid 19 pandemic caused by the βcoronavirus strain causes severe acute respiratory syndrome, to date, there have been 208 million cases of covid 19 and 4.37 million deaths worldwide.
To date, 61 SARS-CoV-2 vaccine candidates have been clinically evaluated and 172 candidates are in preclinical development (WHO, 2020). Various vaccine production technologies have been used in this race using mainly inactivated/live attenuated virus technologies, protein subunits, viral vectors. Some vaccines are developed on new platforms such as based on genetic information such as mRNA that provides genetic information for the body to create antibodies instead of introducing antigens from outside into the body.
1. Inactivated vaccine technology/live attenuated virus
A technology that uses a virus that has been inactivated or weakened to not cause disease, but still induces an immune response. Inactivated vaccine technology is one of the very basic vaccine production technologies and has been used to produce many preventive vaccines such as rabies vaccines, hepatitis B and C vaccines… Inactivated vaccines are divided into two main groups: Inactivated vaccines and live attenuated virus vaccines. Two representative vaccines for this technology are the Vero Cell vaccine (China) (Angeli et al, 2021; Kyriakidis, et al, 2021).
BBIBP vaccine (Vero Cell by Sinopharm)
BBIBP vaccine, also known as Vero Cell, was researched and developed by Sinopharm (China). Sinopharm’s vaccine is researched and produced based on the inactivated vaccine mechanism. The SARS-CoV-2 viruses isolated from patients in Wuhan were cultured in Vero cells to produce large amounts of viral particles, and then chemically inactivated viruses such as β-propiolactone and purified with AlCl3. After being injected into the body, the inactivated viruses will stimulate the immune system to create antibodies and let T cells and B cells remember the SARS-CoV-2 antigen. This is also the reaction mechanism of vaccines such as polio, rabies, hepatitis B… (Angeli et al, 2021; Kyriakidis, et al, 2021).
Live attenuated virus vaccine
Vaccines are created by creating a live version of the virus with reduced virulence and virulence and limited replication for the purpose of not causing disease but able to induce an immune response similar to a natural viral infection. . A decline in viral virulence can be produced by exposing the virus to adverse conditions or by interfering with viral genome editing. The vaccine form has the advantage that it is possible to create aerosol vaccines and they can induce immune reactions in the respiratory mucosa. However, vaccines using this technology also have limitations in safety, taking a long time to clinical trials. The candidate vaccine candidate using this technology is Covaxin being developed by Codagenix and the Serum Institute of India (Kyriakidis, et al, 2021).
Protein subunit vaccines
Protein subunit vaccines are developed through recombinant protein antigens (Spike proteins). The S protein subunits are produced by recombinant DNA technology on heterologous expression systems such as bacterial or mammalian cells, in which the S spike proteins are isolated and purified after culture. inoculation of a large amount of the SARS-CoV-2 virus. The antigen used is taken up by adjuvant activated antigen-presenting cells (APCs) and presented to adaptive immune cells (Kyriakidis et al, 2021). Vaccines researched and manufactured using recombinant microprotein technology have higher safety than inactivated virus vaccines/live attenuated virus vaccines (Kyriakidis et al, 2021).
According to information published from Nanogen, the NanoCovax vaccine uses protein subunit vaccine technology, in which the recombinant protein S subunit is mounted on silica nanoparticles. Instead of using the entire pathogen, a subunit vaccine is a vaccine that uses only harmless fragments of the antigen (protein) of the microorganism to stimulate the appropriate immune response. To create a sub-unit vaccine, the transmembrane domain of protein S is removed and protein S acts as a protein cargo (protein cargo) carrying the antigenic proteins S, M, E, N of SARS-COV- 2 to stimulate the immune response. It is expected that the NanoCovax vaccine will be included in the national immunization program by the end of 2021. Another vaccine candidate that has been successfully tested is Covavax of the US (nanogenpharma.com).
3. Vector vaccine technology
Vaccines using viral vector technology are manufactured using a harmless Adenovirus (which has been engineered to express a spike protein and cannot replicate) as a vector carrying the gene encoding the SARS-S spike glycoprotein S- CoV-2. The host-virus produces spike protein and is expressed on the cell surface. Therefore, when injected into the body, the above viruses will also stimulate the immune system to work, helping the body to respond better. Virus vector vaccine technology has been applied to produce many types of vaccines such as influenza virus vaccines, Ebola… The representative vaccines for this technology are AstraZeneca, Janssen, sputnikV vaccines (Kyriakidis, et al, 2021).
The vaccine ChAdOx1nCoV-19 with the trade name Vaxzeria or Covisheld was developed and produced by Oxford and AstraZeneca universities based on virus vector technology. The company used the adenovirus ChAdOx1 (a chimpanzee Adv that has been modified to be unable to replicate and cause disease) as a vector carrying the gene segment encoding the spike glycoprotein S of SARS-CoV-2.
The effectiveness of the vaccine is 89.6%. One study showed that using a low dose instead of the standard dose for the first injection increased the effectiveness of the vaccine by up to 90% (Healdata.org), AstraZeneca was also effective against Alpha, Beta, Delta variants. with an efficacy of 94% in reducing the number of hospitalizations due to the Delta variant and showed no deaths among those vaccinated.
This vaccine was determined to be safe in clinical trials. However, when vaccination is widely deployed, the occurrence of post-injection coagulation syndrome is very small, related to the appearance of anti-PF4 antibodies that cause platelet activation (Greinacher et al, 2021).
Vaccine Janssen (Johnson & Johnson)
Ad26-CoV2-S vaccine, also known as Janssen vaccine, is researched and manufactured by Janssen Pharma Ceutica and Beth Israel Deaconess Medical Center. Janssen vaccine is also the only vaccine so far with a single dose.
The Janssen vaccine was also developed using virus vector technology, using the Ad26 virus (the type of adenovirus that causes colds in humans) to transport the gene encoding the spike protein of SARS-CoV-2 into cells, then transcribe and Expression of spike protein on the cell surface. The mechanism of action of the Janssen vaccine is similar to that of the AstraZeneca vaccine (Kyriakidis, et al, 2021).
Janssen vaccine was effective 66.1% (14 days after injection) and 66.9% (28 days after injection). It is 85% effective at preventing serious illness and 100% effective at preventing death (healthdata.org). Like AstraZeneca, the J&J vaccine has problems with a rare post-injection thrombosis syndrome, which can sometimes be fatal.
Vaccine Sputnik V (Russia)
Sputnik V, also known as Gam-CoVid-Vac, was developed by the Gamaleya Institute of Epidemiology and Microbiology, Russia. Sputnik V also uses the same technology as the vaccines of AstraZeneca and Johnson & Johnson. However, there is a difference in Russian vaccine production technology compared to the two above companies in the two doses when using two different viral vectors. The first dose of the vaccine is produced using the Ad25 vector, the second dose of the vaccine has the Ad26 vector to increase the immune response and avoid the weakness in the human body that already has anti-adenovirus antibodies (because Ad25 is a virus). colds in humans).
According to the data published in the aggregate report at healthdata.org, Sputnik V has protection effectiveness of 91.6%. The effectiveness of preventing serious disease is 100% (Yan, et al, 2021). Antibodies of this vaccine have the ability to neutralize different variants of the virus up to 70%.
4. Vaccine mRNA
The mRNA vaccine contains a modified mRNA fragment encoding the surface spike protein of SARS-CoV-2, encapsulated in lipid nanoparticles to increase durability and immunity. After the vaccine is injected into the body, the lipid nanoparticles release mRNA into the host cell, the host cell’s ribosome translates the production of viral spike proteins and is expressed on the cell surface. The spike proteins stimulate the immune system to produce antibodies and help T cells remember antigens. (Kyriakidis et al, 2021).
Two typical Covid-19 vaccines using mRNA vaccine technology that have been approved by WHO for use are the vaccines of Pfizer/BiONTech and Moderna. In addition, two other vaccines, CureVac and Arcturus, are in phase III clinical trials.
BNT162b2 has the trade name Comirnaty, but in Vietnam it is often called the Pfizer vaccine. Pfizer vaccine is researched and manufactured using mRNA vaccine technology, encoding P2 spike protein and prepared as RNA-lipid nanoparticles of nucleoside-modified mRNA. BNT162b2 induces activation of the influenza innate immune sensor and thereby increases antigen expression (Lamb et al, 2021).
BNT162b2 A phase 3 clinical trial involving more than 43 thousand people showed that the vaccine was 95% effective (from 90% to 100% in all age groups, sex, ethnicity, underlying medical conditions, etc.) (Polack et al. al, 2020). Validity for each variant: Beta 75.0% (Abu-Raddad et al, 2021), Delta and Alpha are 88% and 93%, respectively (Bernal, et al, 2021).
The Pfizer vaccine can cause mild to severe side effects and allergies. In addition to the common injection site and systemic side effects, there is a small incidence of myocarditis and pericarditis in male adolescents, occurring within a few days of injection with symptoms of chest tightness and dyspnea. heart beat fast.
The vaccine of Moderna is also researched and manufactured using the same mRNA vaccine technology as Pfizer’s technology vaccine, so it has the same mode of action as Pfizer. However, mRNA-1273 is more stable, therefore, the storage conditions of the Moderna vaccine are less manageable than that of Pfizer (-20oC), therefore, it may be favorable to administer in a normal refrigerator.
The effectiveness of the Moderna vaccine reached 94.1%. The two current mRNA vaccines are equally effective, but mRNA-1273 provides easier protection and lower response rates.) Therefore, mRNA-1273 is expected to be used preferentially at a later stage, when a COVID-19 vaccine is out of stock (Healthdata.org). Regarding the responses after injection, Moderna also had reactions such as fever, muscle pain, and fatigue like other vaccines.
Tài liệu tham khảo
- Angeli, F., Spanevello, A., Reboldi, G., Visca, D., & Verdecchia, P. (2021). SARS-CoV-2 vaccines: Lights and shadows. European journal of internal medicine, 88, 1–8. https://doi.org/10.1016/j.ejim.2021.04.019
- Kyriakidis, N.C., López-Cortés, A., González, E.V. et al. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. npj Vaccines 6, 28 (2021).
- WHO. Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under Emergency Use Listing Version 15 June 2021.
- Lamb, Y.N. BNT162b2 mRNA COVID-19 Vaccine: First Approval. Drugs 81, 495–501 (2021).
- Polack FP et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 2020, 383 2603–2615.
- Abu-Raddad LJ et al., Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N Engl J Med. 2021.
- WHO, Evidence Assessment: Sinopharm/BBIBP COVID-19 vaccine https://cdn.who.int/…/2_sage29apr2021_critical-evidence….