How vaccines work, with examples of COVID vaccines: mRNA vaccine (Pfizer, Moderna), DNA & Viral vector vaccines (Johnson & Johnson (J&J, JNJ), Oxford-AstraZeneca, Inovio, Sputnik V); protein/peptide vaccine (Novavax, EpiVacCorona), conventional inactivated (CoronaVac of Sinovac, Covaxin, Sinopharm). Mechanism of each type of coronavirus vaccines explained. Vaccine-induced immune response as compared to natural immunity.
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During a natural viral infection, infected cells alert the immune system by displaying pieces of viral proteins on their surface. They are said to present the viral antigen to immune cells - cytotoxic T-cells, and activate them.
Debris of dead cells and viral particles are picked up by professional antigen-presenting cells, (dendritic cells...). Dendritic cells patrol body tissues, sampling their environment for intruders. After capturing the antigen, dendritic cells leave the tissue for the nearest lymph node, where they present the antigen to another group of immune cells - helper T-cells. Viral particles also activate B-cells.
These cells mount 2 types of immunity specific to the viral antigen: cell-mediated immunity and antibody-mediated immunity.
Vaccines deliver viral antigens to trigger immune responses without causing the disease. The events of a vaccine-induced immune response are similar to that induced by a natural infection, although some types of vaccines may induce only antibody-mediated immunity (B cell immunity, not T cell (cellular) immunity).
Many existing vaccines contain a weakened or an inactivated virus. Because the whole virus is used, these vaccines require extensive safety testing. Live attenuated vaccines may still cause disease in people with compromised immune systems. Inactivated vaccines (Sinovac/China, Covaxin/India) only induce humoral (B cell) immunity.
Subunit vaccines contain only part of the virus, usually a spike protein (peptide - EpiVacCorona/Russia). These vaccines may not be seen as a threat to the immune system, and therefore may not elicit the desired immune response. For this reason, certain substances, called adjuvants, are usually added to stimulate the antigen-presenting cells to pick up the vaccine.
Nucleic acid vaccines contain genetic information for making the viral antigen, instead of the antigen itself. Naked DNA vaccines (Inovio, phase 2/3 clinical trials) require a special delivery method to reach the cell’s nucleus (electroporation). Alternatively, a harmless, unrelated virus may be used as a vehicle to deliver the DNA. In this case, the vaccine is also known as viral-vector vaccine (Sputnik V/Russia, Oxford-AstraZeneca, Johnson & Johnson's). For example, the Oxford-AstraZeneca Covid-19 vaccine uses a chimpanzee adenovirus as a vector. The adenoviral genome is modified to remove viral genes, and the coronavirus spike gene is added. This way, the viral vector cannot replicate or cause disease, but it acts as a vehicle to deliver the DNA. Why a non-human adenovirus is used?
Do DNA vaccines change human DNA?
mRNA vaccines (Pfizer, Moderna) are delivered within a lipid covering that will fuse with the cell membrane. The mRNA is translated into viral antigen, which is then displayed on the cell surface. mRNA vaccines are extremely unlikely to integrate into human genome.
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