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The number of diseases we’ve beaten back using vaccines is truly impressive.
But when it comes to beating back viruses themselves, our track record is actually…
a lot less consistent.
Take measles.
It’s a severe, highly contagious disease that used to be considered an inevitable part
of childhood until vaccination was introduced in 1963.
The measles vaccine saves millions of lives, and according to the CDC, two doses is usually
enough to protect kids for life.
Influenza is a nasty bug too.
But unlike measles, which is known as the poster child for lifelong immunity, influenza
is the only vaccine-preventable disease that requires a fresh shot every year.
C’mon flu, why can’t you be more like measles and let us fight you off with just
a couple of doses?
What makes these two viruses so different that we can fend off one of them permanently
in one or two steps, while the other requires constant vigilance?
It has to do in part with the structure of these viruses, and how mutation causes them
to change.
The measles virus is shaped kind of like a ball covered in spikes.
And those spikes are proteins, named mico and fusion proteins, or H and F for short,
which help the virus latch onto a host cell and infect it.
And if H or F undergo a genetic mutation, the measles virus suddenly gets much worse
at infecting.
Researchers are still studying the details of how this works in measles, but the genetic
sequence of the virus determines the structure of those proteins.
And if that structure changes even a tiny bit, in measles, they appear to stop working.
The point of any vaccine is to trigger the immune system to create antibodies to specific
disease-causing agents, which then lie in wait to fend off microbes with the same antigen
if and when they invade the body in the future.
And in measles, these H and F proteins can’t change.
Which is pretty great for us, because we just need to produce one vaccine, and that’ll
pretty much work for everyone, forever.
In fact, the vaccine we use today was developed using a strain of measles that was first isolated
from a young boy in 1954.
And it still works really well!, because measles today still looks enough like measles from
1954 that the same antibodies still work to fend off the illness.
Influenza viruses, on the other hand, are the quick-change artists of the viral world.
Like measles, the types of influenza our vaccines target have two kinds of protein spikes.
Hemagglutinin, or HA, helps the virus bind to the host cell.
There’s also neuraminidase, or NA, which helps release viruses from the host cell.
HA and NA together make up the HN formula we name flu strains after — like H1N1.
But unlike its counterpart in the measles virus, HA mutates a lot.
Mutations change the shape of this protein, and it changes so quickly that an antibody
that worked for one subtype of flu can’t recognize the shape of other variants.
Our once-a-year flu vaccines trigger production of antibodies to the head of the HA protein,
which reaches out from the surface of the virus like a bunch of tiny mushrooms growing
on a roughly ball-shaped virus.
These antibodies work by blocking the HA protein from binding to host cells.
But like the measles virus, flu virus HA proteins mutate all the time, causing slight changes
in their structure, while still retaining their ability to infect us.
And the fact that the structure is constantly
changing means the same antibodies can’t recognize the HA molecules on different strains
of flu from one year to the next.
A truly universal flu vaccine — a one-time vaccine that would be effective across all
strains — is widely considered the holy grail of vaccine research.
One big piece of the puzzle is the stem of the mushroom-shaped HA protein.
Unlike the rapidly-changing head, the stem remains largely unchanged from year to year.
If only our antibodies could reach it.
Because that mushroom head seems to get in the way.
In researching the H1N1 pandemic of 2009, scientists found something unexpected.
They realized that people who got the 2009 version of the flu shot made more antibodies
than they would have predicted to the HA mushroom stems.
And surprisingly, those antibodies were able to recognize and immobilize several strains
and subtypes of flu.
It turns out that the particular strain of H1N1 circulating that year had a head that
was about 30% different from previous strains, which has led scientists to hypothesize that
being exposed to HA proteins with different kinds of head structures somehow redirects
the body’s immune response to make antibodies that bind to the stems.
So, developing vaccines that target the stem of HA has since been a major focus of universal
vaccine efforts.
One approach is a vaccine that targets the HA stem, in combination with NA, which has
shown to protect against a lethal strain of flu in mice.
Another promising approach uses antibodies from … llamas.
Turns out llamas produce antibodies that are smaller than ours, which allows them to squeeze
past the HA head and bind to the stem.
This approach also proved successful in mice.
But the candidate furthest along in the quest for a universal shot is called M-001, and
it’s slightly different.
It targets very short segments of the HA protein that are known not to change.
And it’s making its way through clinical trials.
Ultimately, the process behind creating a universal flu vaccine could end up being a
lot like how we made the measles vaccine.
It’s just that the flu makes things far more difficult, and hides the parts we can
target really well.
Meanwhile, we’ll stay thankful for our lifelong immunity to measles, and keep getting those
annual flu shots.
They’re still a lot nicer than the flu.
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