ChAdOx1 - SARS-Cov-2 Vaccine - Preliminary Report

imhotep

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  • Mar 29, 2017
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    If anyone did miss the previous post on the preliminary results of the mRNA-1273 vaccine by Moderna please read -
    https://elakiri.com/threads/an-mrna-vaccine-against-sars-cov-2-—-preliminary-report.1945543/

    The current post is about the ChAdOx1 vaccine (also called the AZD1222) developed by the Oxford University.

    Recently, they released the preliminary results of their Phase I/II studies.

    This vaccine is an Adenovirus Vector Vaccine - The adenovirus vector used has an inserted gene that encodes the full-length SARS-CoV-2 spike protein.
    The idea to use an adenovirus as a vector to deliver the vaccine is simply because the virus can enter the human cells quite easily by attaching with the host receptors and then release their gnome in to the human cells. So this particular vaccine, once inside the human cells will start producing the spike protein. (because it's modified to do so)
    The produced spike protein then acts as an antigen to prime the body immune system to recognize SARS-CoV-2 if it infects the body at a later date.

    But there's a small snag in the above scenario. There are several adenoviruses that affect us, and many people have adenovirus-specific antibodies that could bind and neutralize these vectors. So the research scientists at Oxford used a clever approach. They used an adenovirus of chimpanzee origin that does not normally infect humans. Hence we would not likely have pre-existing antibodies to the adenovirus vector used. They also changed the adenovirus itself by the deletion of TWO genes. One of the genes deleted is the one regulating the virus replication - this makes sure that virus cannot create an infection in human cells, and the second deletion was to get the space to insert the gene that will code for the SARS-CoV-2 spike protein.

    They used 1,077 healthy adult volunteers aged 18-55 who were randomly assigned to receive AZD1222 or a control vaccine. A small group out of this were given 2 doses.

    The basic findings were....

    Side effects were mild to moderate, mostly consisting of pain and tenderness at the site of injection.
    All recipients of a single dose produced high levels of spike protein-specific total binding antibodies that were sustained to day 56 post-vaccination,.
    Those recipients who received 2 doses (28 days apart) - the second dose boosted the levels of existing total binding antibodies and induced neutralizing antibodies.
    A single dose induced high levels of spike protein-specific T cell responses in all subjects through day 56 post-vaccination. A second dose did not boost any further.

    To sum up - The results of the trial are reassuring; the vaccine seems to activate both arms of the adaptive immune response by inducing both neutralizing antibody and T cell responses specific to the SARS-CoV-2 spike protein.

    Note - Previously they did a Challenge experiment with rhesus macaques who were immunized with this vaccine. These macaques infected with SARS-CoV-2 had no signs of virus replication in the lungs, significantly lower levels of respiratory disease, and no lung damage compared to control animals. It's reasonable to assume that if it worked with a monkey then there's a fair chance that it will work for a human.