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    How the puzzle of viral vector vaccines was solved, leading to today’s COVID-19 shots

    Viral Vector Vaccines Vaccines use safe viruses to insert pathogen genes into cells to generate an immune response. Credit: Shutterstock

    If you don’t know what pieces to use, how many pieces you need, what the puzzle will look like when completed, or what features the puzzle may perform, how do you solve the puzzle?

    I faced these challenges in 1969 when I was working with human adenovirus 5 (Ad5) as a postdoctoral fellow in Canada in the laboratory of the Dutch molecular biologist Alex Van der Eb. When he returned to Canada in 1973, he continued to study Ad5 in the Cancer Research Group of the Department of Biology and Pathology at McMaster University.

    The perpetual technology he developed will continue to serve humanity in many ways. Some of them are still emerging today, but one stands out more than the others: Graham’s Ad5 vector It serves as a global platform for COVID-19 vaccines, including Canada-approved AstraZeneca and Johnson & Johnson vaccines.

    Viral vector

    The puzzle that Graham solved was to create a valuable viral vector. A fine Trojan horse that is easy to assemble, can be manufactured in large quantities at low cost, and remains stable at normal refrigerator temperatures.Most importantly, it is efficient in transferring foreign DNA to Mammalian cells-Including humans cell..

    Viral vectors are modified viruses that trigger the body’s defensive response without causing infection. These virus-like entities usually cannot be replicated, Achieve a natural and intact virus, but no infectious destruction..They can enter Human cells And instruct the machines of those cells to express gene Carried by vectors, it allows cells to make and export proteins encoded by those genes. All of this is done without permanently modifying the host cell.

    This means that when a COVID-19 viral vector vaccine is given, it can express the COVID-19 peplomer integrated into the vector’s genome. This allows affected cells to present the COVID-19 protein antigen to the human immune system, stimulating immune defense against COVID-19 infection.

    Viral vectors elicit a very strong immune response. They produce both neutralizing antibodies to prevent infection and killer T cells (cytotoxic T cells or CTLs) to destroy COVID-19-infected cells.

    Some recognized, non-duplicate Viral vector Has become Developed for vaccines.. These are retrovirus-based vectors including those based on adenovirus, adeno-associated virus, herpesvirus (such as cytomegalovirus) and vaccinia virus, and others based on Moloney murine leukemia virus and modified lentivirus (HIV). Is included. All of these have been used in both gene therapy and vaccine delivery clinical trials with varying success.

    However, for effective large-scale use as a safe vaccine, adenovirus-based viral vectors ( catch a cold) Or vaccinia virus is preferred. In the field of COVID-19 vaccine, The most prominent are based on adenovirus vectors.. This is where Graham’s discovery begins.

    Puzzle piece

    As the first piece of the puzzle, Graham developed a way to transfer foreign DNA (in this case, a piece of the human adenovirus subtype 5 genome) into a cell.

    Article explaining this technique It has been cited by more than 10,000 researchers since it was published and has become one of the greatest hits in modern science.

    Since viral vectors usually do not replicate, the challenge was to extend (replica) the vector for manufacturing and vaccine production. Vectors need living cells to host them, bid on vectors, and allow them to replicate. All that was needed was a self-permanent cell line transplanted with a modifiable virus or vector.

    This was solved by Graham’s second approach. At McMaster University, he used DNA transfer technology to establish a stable, proliferative and easy-to-manipulate human cell line called HEK293 cells that permanently contained the genes required for proliferation of replication-deficient vectors. .. Graham’s article on this cell line is another classic article with over 6,000 citations...

    HEK293 cell lines and their derivatives are currently used worldwideVaccines and many other biologics are manufactured in both industry and university and government laboratories.

    As a third approach, Graham has prepared a stable and robust molecular biology tool. Easy creation of stable adenovirus vector with foreign gene inserted It can handle up to 8,000 base pairs (individual units of the genetic code) of foreign genetic information. This is enough data to produce the most useful proteins. It is used for both gene transfer and expression (gene therapy) and vaccine delivery, as seen with the COVID-19 vaccine.

    In the case of vaccines, it has become possible to take the virus that causes the symptoms of the common cold, remove the gene that can reproduce it, and replace it with a gene from an infectious pathogen such as another virus that is the ultimate target of the vaccine. These added genes cause the production of harmless elements of the target virus. The body then recognizes and attacks this element to generate immunity. For the COVID-19 virus, this element is a protein spike.

    Assemble the puzzle

    These advances were achieved with human adenovirus 5. It was then applied directly to the COVID-19 vaccine developed by Can Sino in China and Sputnik V vaccine in Russia. This process is also indicated for other adenovirus subtypes of the COVID-19 vaccine. These include the chimpanzee adenovirus vector vaccine developed by Oxford University and AstraZeneca, and the human adenovirus 26 vector. vaccination Developed by Johnson & Johnson.

    Graham, now retired and living in Italy, certainly knew how to build a puzzle. Half a century after the first successful construction of viral vectors, billions of people around the world are grateful for protecting them from pandemics today. virus..


    Q and A: How different types of COVID-19 vaccines work


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    Quote: How the viral vector vaccine puzzle is solved, today’s COVID-19 shot (October 18, 2021) from https://medicalxpress.com/news/2021-10-puzzle-viral-vector-vaccines Acquired on October 18, 2021. -today.html

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