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Why Do I Need Another Flu Shot?

February 29, 2020


[MUSIC PLAYING] PROFESSOR: –discussion
of Monte Carlo stimulations and how
each time you do it, you get a different trajectory. But if you average it all out,
you can make sense out of it. Remember that? That’s the way our
immune system works. There’s a huge
amount of randomness, chance, individual differences,
but it averages out. And our immune
systems are designed to repel foreign invaders– bacteria, viruses, fungi. And it’s designed so that
every individual may not be resistant to an invader. That is the flu
epidemic that I’ll talk about, killed
somewhere around a third of the population. But it’s designed
so that enough of us survive that we can reproduce. Because remember,
despite everything you’ve heard in the course, our
main purpose is to reproduce. That’s where Charles
Darwin told us. OK, so we all have
an obligation. I’ve done it already. So I want to– how do you teach
business students– and even biologists–
the immune system? And I’m going to
start with vaccines, and I’m going to start
with some biotech product that I hope all of you
have taken recently. How many of you have gotten
this year’s flu vaccine? OK. How many got last year’s
flu vaccine as well? Good. How many can tell me
what a flu vaccine is? Press your button. STUDENT: It’s an inactivated
form of a pathogen. PROFESSOR: Right it’s an
inactivated form of flu virus. But why do we have
to get it every year? Keep going. STUDENT: Because it mutates. PROFESSOR: It changes. Every flu is different. And let me explain
how this happens, and then what the antibodies
are that our body produces as a result of the vaccine
to make us immune to flu. So here is the virus. It’s very, very tiny. It has a lipid coat and a
bunch of spikes on the surface. Like all viruses, it cannot
replicate on its own. The only way it can replicate
is invading a cell– generally something in
our nose or in our lungs– replicating, and
the daughter viruses go on and infect other cells. And, you’re right. It’s a killed– or inactivated–
bacteria, or, in this case, virus. And it’s a huge problem. And flu is fairly
simple to solve. Many of you read the newspapers. You’ve got an Ebola epidemic
going on in the Congo. There are Zika
viruses all around. Just beginning to develop
vaccines for them. So just, let’s take a
little closer look at it. What vaccines do is trigger
the induction of antibodies, these serum proteins–
proteins that are circulating in our blood– that bind to the specific virus. Not every strain of influenza,
but the very specific types of influenza virus
that are current. And by binding to the viruses,
they will cause inactivation– either preventing the virus
from infecting a cell, or leading to the death
of the virus, or both. But each strain of flu– as I’ll tell you, show you– is different. You remember H5N1? Can you tell me what H5 means? I’ll tell you in a moment, OK? So each one is different. So the first thing
to keep in mind is we make these
antibodies that will kill the particular strain of
virus that we’re infected with. The second thing–
and I’ll stress this– the immune system has a memory. Once you’ve encountered
that particular virus, the cells that
make the antibodies stick around for long periods
of time, sometimes forever. So that if you ever
re-encouter the same virus, they will immediately
make antibodies and repel the invader. So there’s specificity
and there’s memory. And the virus–
like all viruses– has a nucleic acid
as its genome. In the case of
influenza virus, it has eight RNA molecules that
code for 11 viral proteins. So it’s not a single genome. That becomes important. But it’s eight
different genomes. And the proteins
that are immunogenic are the two proteins on
the surface of virus. They’re called
hemagglutinin– or H– and neuraminidase–
which is N. And these are involved in infection
of the virus into a cell. But these are the ones that
change from one strain of virus to another. So H5 means hemagglutinin 5. N1, neuraminidase 1, and so on. And you’ll remember–
maybe you’ll remember that some
of these strains originated in Asian
countries where there’s a mixture of
ducks and people and pigs and all of that. And there’s a reason for
it, because the virus, it’s like financial engineering. It’s viral engineering. The virus has eight RNA genomes. And if two different viruses– say, an avian virus, a bird
virus, and a human virus– infect the same cell,
the virus that comes out can have some green– some purple RNAs
and some red RNAs, and it will make a
mixture of proteins. And that’s what happens. That’s how the virus changes
from one year to another. It incorporates a
piece of a bird virus and a piece of a pig virus by
just re-assorting its genome. OK? But every year, they– the people in charge of
vaccines at the CDC in Atlanta, yeah, question, go ahead. And use your microphone. We’re recording this. Thank you. STUDENT: The re-assortment takes
place while the virus is inside of a host of a certain species? PROFESSOR: Correct. STUDENT: But also incorporates
from another species? PROFESSOR: Precisely. If two viruses infect the same
cell, the virus that comes out will be an admixture. It will have the
hemagglutinin gene from one virus, the
neuraminidase for another, and that’s why it
spreads so rapidly. And, you know, again, you have
the Asian flu, Hong Kong flu, many of these
originated in places– certainly markets–
they had to close down all of the markets in Hong Kong
and several other Asian cities for a while to prevent this. And it may surprise you
that the classical– virtually all vaccines– are made by growing
the virus in hen eggs. And the reason is, this
is the original way that vaccines were made. A lot of viruses grow
in egg-based systems, and they harvest the
virus from live eggs and purify it, and
then kill the virus. It’s only recently that
molecular biology has impinged on the vaccine business. And as you can see, only
about seven years ago did we grow viruses in mammalian
cells rather than hen eggs. And right now, the way to do
it is using recombinant DNA techniques. That is, all you
need to inject are the two proteins–
the hemagglutinin and the neuraminidase. You don’t need the
rest of the virus. And that’s what’s
being done now. But it’s the
recombinant flu vaccine, it’s the only egg-free
vaccine on the US market. So that gives you an idea of
what vaccines are, but then– and this will be the last slide
before I stop for questions– there’s a memory. So if you inject what
we call protein A– which could be this flu virus– it’ll take about a week or
two before the body responds by making enough of these
antibodies to kill the virus. And that’s why you get sick
and eventually you recover. If you have the flu–
unless your immune system is weakened– after a week or
so you begin to recover. And that’s the time it takes
to make these antibodies. And I’ll tell you
why it takes a week. But, years later, if you’re
infected with the same flu– the same A– you get
a much larger response and a much quicker response. And that’s because you
have these memory cells. We’ll describe them as memory
B cells that are waiting– and waiting patiently–
for something to trigger their proliferation
in making antibodies. And that is what it
means to be vaccinated. So let me just pause here
to see that you got this. And then we’ll go on
to what an antibody is, because it’s a weird protein. Any further? OK, yes. STUDENT: Is an implication
of a critical mass of sorts that if it’s humans are
mixing these things, is it going to get
worse and worse? PROFESSOR: It’s– Well, it– usually, avian viruses or pig
viruses don’t infect humans. But if they pick up
a hemagglutinin that can bind to a human cell,
it’s all random admixtures and who gets exposed. But, yes. As– and particularly now as
people travel from continent to continent, you saw
what happened with Ebola. I mean, the whole
country was freaked out by a few cases that
were imported from Africa. So, you know, we do have to be
prepared for these pandemics. And you see what’s
going on in Congo right now where
there’s civil war and they can’t get the vaccines
to people who need them. OK, yes. STUDENT: What’s sort
of constraining us from finding sort of a
universal approach to influenza? I understand the
HNN recombination. PROFESSOR: Because
each molecule, there are common structural
features, but the parts that specify infection–
in other words, you need to buy an antibody to
the part of the protein that’s involved in infection, and
that is highly variable. And the same is true not just
of influenza, but of HIV. I mean, HIV is very good,
because it mutates to escape. We make antibodies if
you’re infected with HIV. You’ll make antibodies,
but to the strain that infected you months
ago, and not the new one. So it’s a constant
Darwinian selection, where the immune
system is constantly struggling to make antibodies
against something it’s never seen before. And that’s the problem,
and that’s the fascination with the immune system. It can make antibodies
to something it’s never seen or
never existed before. And how do we do that? [MUSIC PLAYING]

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