Coronavirus vaccine (SARS-CoV-2) delivered for clinical trials – mRNA Vaccine against COVID-19

Coronavirus vaccine (SARS-CoV-2) delivered for clinical trials – mRNA Vaccine against COVID-19


An American company “Moderna” has
released first batch of vaccine against novel coronavirus, against this SARS2
coronavirus. This vaccine is actually in phase 1 clinical testing. What I mean by
this is that before our drug is launched firstly, it is discovery and preclinical
phase. In this phase, it is tested in labs and on experimental animals to observe any adverse effects in animals and after that human
trials or clinical trial starts, starting from Phase 1, this drug, our vaccine, it is
given to very small number of volunteers, 20 to 100 volunteers and they are observed
to see, if any adverse effect develop then gradually bigger population is
chosen, 100 to 300 volunteers, in Phase 2 and 300 to 3000
volunteers in Phase 3 and if all goes well it can be finally approved by
FDA for public use, then it is marketed for public use and it is launched. So, right
now, this vaccine, it is in phase 1. So, it may take up to year or so before it
would be available for the general public. The interesting thing about this
vaccine which is launched by “Moderna” is that, it is “mRNA vaccine” unlike the
traditional vaccines that are either live attenuated virus or protein subunit
vaccine. It is mRNA vaccine and mRNA or messenger RNA as you know, it codes for unfused stable unfused “S” protein or spike
protein of coronavirus, and by the way this vaccine is called
“mRNA1273”. So. what happens is that, as I have told you in the lecture
visual lecture on the replicative cycle of coronavirus that, this here is the
corona virus and here is its “S” protein, what will happen is that through
its “S” protein it will bind with ACE2 receptor of type 2 alveolar
pneumocytes and this will lead to fusion of this viral membrane, viral envelope
with cell membrane and it will enter into cell and it will infect the cell. So,
with this vaccine we target this step. So, we target this step with this
vaccine. So, today we will discuss that how this mRNA vaccine will work.
Hello, I am Dr. Aizaz from medicovisual.com! Welcome to this visual lecture! So,this vaccine, let’s suppose this vaccine is given through intramuscular injection in deltoid, so, I am gonna enlarge this part
and we will see that what is going on inside this deltoid. So, here is the
vaccine and it has been dropped inside the interstitial space, the space between
cells.So, this vaccine, it actually contains mRNA which is encapsulated by
lipid nanoparticles. So, mRNA is present inside a lipid nanoparticle, why do we
need this lipid nanoparticle? Because if we give / insert a naked mRNA, if we
inject a naked mRNA, what will happen there are some hostile
RNAses that are present in the extracellular environment, which will digest this. RNAses mean RNA digesting enzymes. They will digest this. Secondly, we
need mRNA inside the cell to function, there is no need, there is no use
of mRNA outside the cell, it may even trigger immune response
against itself which will render the vaccine useless. So, mRNA by itself cannot
enter into cell. So, this lipid nanoparticle it will be used as a
delivery vehicle, it will be used as a delivery vehicle to safely deliver this
mRNA inside the cell, it will release the mRNA inside the cell and it itself will be
digested here. So, now we got the mRNA, this mRNA vaccine, it imitates
an actual virus infection. Just like an actual coronavirus
which infects the cell and injects its mRNA inside the cell. It is acting just
like that, it is so natural. But the difference is that it codes only for “S”
protein it is not coding for any other pathogenic proteins, So, of course it
cannot cause the disease but it can trigger immune response. So, here is
the mRNA, it will use cellular protein synthesizing machinery. So, to form what?
to form “S” protein or spike protein of coronavirus. This spike protein will be
processed by intracellular proteases and this after processing the fragments of “S”
protein, they will be presented on MHC-1 protein. They will be presented on a
special receptors called MHC-1. Actually, all nucleated cells have to present or express their cellular
proteins on MHC-1 receptors, This is, to show the immune system that
what is going on! What protein is being synthesized inside these cellular
factories. Of course normal cell will present normal cellular
proteins on MHC-1 and viral infected cell or in this case vaccine infected cell
will, of course, present on MHC-1, it will present viral
proteins or fragments of “S” protein In this case. Some of this
proteins will be presented on MHC-1 while most of it will be packed by
Golgi apparatus, processed by endoplasmic reticulum and will be packed by Golgi
apparatus and these “S” proteins, they will be secreted outside the cell. So,
they will be secreted outside the cell. Now, let me tell you something
interesting! Billions of cells, billions of cytotoxic
cells with millions of different specificities are wondering in your body.
they are wondering in plasma and they are trying to find their target. Somehow,
a cytotoxic or killer cells, cytotoxic T cell which may be specific for this “S”
protein, it may come across this “S” protein randomly and it will bind with
its T cell receptor, with its “TCR” or T cell receptor. It will bind with this MHC-1
bound “S” protein fragment, MHC-1 bound antigen and it will become active.
The cytotoxic T cell it is also called CD8 positive lymphocyte because it is a
lymphocyte which expresses CD8 protein. So, it is cytotoxic T cell. Cyto
means cell, toxic means killer. So, it is cell killer, we will see what it does. So,
this cytotoxic T cell will recognize it and will become
active, will become happily active. Not only cytotoxic t-cells are present here
in our body, we also have B-cells. So, these cells or B lymphocyte, they are
not fussy about MHC-1. So, they can directly recognize, they can directly
recognize the antigen and become active. So, cytotoxic T cells which are
responsible for cell mediated immune response and B cell which are
responsible for humoral immune response or antibody mediated immune response.
So, once they will bind with this antigen, B cell, they will bind with this antigen,
they may become activated and they may convert into plasma cell and they will
secrete antibodies specific for this “S” protein. Now, if we also have
some macrophages wondering here and so, these macrophages they will
recognize these foreign proteins. What are foreign proteins?
These “S” proteins. They will recognize these “S” proteins and they will engulf
these “S” proteins and then they will present these “S” proteins on MHC type 2
receptors, not on MHC-1, on MHC-2 receptor. Here is the MHC
1 receptor and they are present, they are expressed on all nucleated
cell, while MHC-2, they are expressed only on professional antigen presenting cell,
for example, dendritic cell and macrophages. MHC-1, they are involved in
expressing endogenous protiens, while MHC-2, they are involved in expressing
exogenous proteins. What are endogenous proteins? Endogenous proteins are
those proteins which are synthesized and processed inside the cell, they are
synthesized inside the cell while exogenous proteins are those which are
taken up by macrophages from the extracellular environment, from the
extracellular environment. They are engulfed and presented on MHC type 2, so,
as soon as they will express these antigens, antigenic fragments on MHC type 2, as protein fragments on a messy type 2, they will take them to helper T
lymphocyte and here come the master of immune system! Helper T lymphocyte is
master regulator of immune system or we also call it that it is “Orchestrator of
immune system”. It is most important cell in immune system. So, helper T lymphocyte
is also called CD4 positive T lymphocyte because it express CD4 receptor. So,
with its T cell receptor it will recognize and bind with, it will
recognize and bind with MHC-2 presented antigen, MHC-2 bound antigen. Now, what it
will do? Now, it will give some orders to cytotoxic T
cell as well as B cell. It will release certain cellular messenger or cellular growth factors or we call them cytokines! It
will release cytokines, which will cause growth and proliferation of cytotoxic T
cell, as well as, growth and proliferation of B-cells. It will cause what? It will cause, clonal proliferation and what I mean by Clonal
proliferation is that, it will make lots and lots of copies of this specific cytotoxic t-cell. It will make lots of copies of
cytotoxic T cell, that is specific for a particular antigen. It will make copy of
cytotoxic T cell, which is specific for this antigen, this “S” protein antigen and
it will also cause clonal proliferation of B-cell and it will also release
cytokines which act on itself and it will make copy of itself as well. So, when
it will make copy of itself, it will lead to massive immune response and it will
lead to amplification of all this immune process. Now, also it will activate these
cells cytotoxic T cells and B cells, so, what will happen that cytotoxic T cells
will release granzymes and perforins that will destroy these
vaccine infected cells, right and after activation, some of these B cells will be converted into plasma cells and plasma
cells are antibody generating factories. So, plasma cell will do what? It will
generate lots of antibodies, which are specific for “S” proteins.
Now, these are the effector cells, this cytotoxic T cell and this cell, plasma
cell, these are effector cells, they are doing something in response to this but
some of these cells, out of these clones they will remain dormant and they will
act when a subsequent infection occur, when subsequent exposure to antigen
occur, when an actual virus infection occur then these dormant cells
will become active and they will do something, they will produce immune
response. These dormant cells are called memory cells. So, we have memory T cells, we have memory cytotoxic T cells, we have
memory B cells and we will have lots of “S” protein specific antibodies and we
also will have memory helper T cells. So, we have got all these things. So,
what will happen when an actual virus enters, so, when actual virus tries to
infect these antibodies will come to our rescue and they will prevent fusion of
this “S” protein with ACE2 receptor of type 2 alveolar pneumosite, it will
prevent fusion. Also these antibodies, they may trigger complement
system and some other pathway, I won’t go into detail and they will they may
directly cause killing of this viral particle and even if somehow
this virus, it may escape this antibody mediated immune response and it enters
the cell and it starts generating and expressing its viral proteins and it
start making lots of copies but because we have memory cytotoxic T cell, they
will quickly and swiftly react and before this virus can release these
virus particles outside the cell. Cytotoxic T
cell will quickly come and destroy the cell and everything inside it. So, of
course, virus will not be able to infect. So, in this way, due to
humoral response or antibody response as well as cell mediated response, this
vaccine can prevent the actual virus infection, actual corona virus infection. Now, here I would love to highlight
another point that, how this mRNA vaccine is better than traditional protein
subunit vaccine. Let’s suppose, if we give an “S” protein directly, we are not giving
mRNA, we are giving “S” protein of coronavirus directly, it may be
recognized by B cell and it may be engulfed and recognized by macrophages and
antibodies will be produced but because it is not mRNA, can it be presented on
MHC type 1? Of course not! because MHC type 1 is only concerned with
presentation of endogenous protein and this is not endogenous protein, this is
exogenous protein, so, will there be a significant cell mediated immune
response or cytotoxic immune response. Of course not, so, this immune response cell
mediated immune response will be negligible but of course we will have
humoral or antibody mediated immune response as well as, of course we will
have helper T lymphocyte. So, because we are not getting a strong cell
mediated immune response, it is not an ideal vaccine, this protein subunit
vaccine because cell mediated immune response is very important in clearing
viral infections, in clearing virus from our body. Now, what about mRNA
vaccine versus live attenuated virus vaccine? Live attenuated virus is
basically living virus, alive virus but it is weakened ,it is weakened
so much so, that it is no more pathogenic! It can trigger immune response
but it cannot cause the disease. We use certain chemicals to weaken this virus. Now, the problem with this is that in
certain real circumstances especially in immunocompromised people, it can suddenly
turn into pathogenic strain and it can cause disease. So, that is a real side
effect especially it has been observed with polio vaccine. So, this was
about this vaccine. Now, this vaccine, it seems quite promising but as of now it’s
safety profile is not clearly elucidated. So, thank you for
watching this lecture! If you like this video lecture, please like this video,
please subscribe to my channel and please give your precious comments
regarding this lecture. Thank you so much for watching this lecture!

Comments

(7 Comments)

  • Johnny Kemmer

    👍

  • Anwar ul Haq

    This is also super lecture

  • Imtiaz Bashir

    This is perfect. Got my immunology concepts clear in just 20 mints. ☺️☺️

  • Imtiaz Bashir

    Immune system is really a blessing 😇😇. Being so super-working, it is so intricate as well.

  • Susanne Brun Madsen

    How to diagnose for SARS-CoV-2? Love this series btw.

  • Parth Lathkar

    Well I am generally not interested in this concept… But watching this video sure has made me develop interest in this regard!!! Subscribing now for more similar content

  • mijimac

    Excelente conferencia, es el vídeo más completo y fácil de entender que he visto sobre el tema, continuaré con las otras conferencias del canal. Muchas gracias por compartir.

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