Happy New Year! This post is a few weeks overdue- my apologies! Blame it on the cold that keeps cycling through my family this month. Anyway, here we go:
Well folks, it’s that time
of year again. Snow is falling softly
from the sky, soup is bubbling on the stove, cookies are baking in the oven,
and my children are… oh god, my children are sick. Again.
In fact, they are on their second cold since November, and for the life
of me I cannot keep enough tissues on hand for their little, runny noses. And I, too, am on my second cold, and
positively drowning myself in Chamomile tea.
At night, I’m nestled in my bed (thanks to NyQuil) while visions of
cough drops dance through my head.
And I. Am. Miserable. I cannot
overstate this. All day long my head
hurts and my sinuses ache. My ears feel
like they might burst and my nose alternates between dripping like a faucet and
stopping up so tight I can’t breathe. I
cough so much my stomach muscles are looking like I’ve spent the last month
doing crunches (hey, silver linings, right?).
And if I am lucky, I will be out of the woods on this one in, oh, about
5-7 more days. Woof. And at the rate we’re going this year, I
might get two weeks of relatively healthy airways before I am taken down again
by the next cold virus that happens along.
This time of year I turn
into a real germaphobe (oh, who am I kidding?
I am a germaphobe all year). I
wash my hands so often they get chapped.
I ramp up the disinfecting of door handles, computer keyboards, and
light switches. I see germs everywhere I
look. The library. The grocery store. My son’s soccer games. My husband and children’s very
existence. I spend the months from
October to April just crossing my fingers and steeling myself against illness,
knowing that the name of the game is ugly survival. Because no one likes having a cold. At best, they are inconvenient and annoying,
and at worst they can put you out of commission for several days, exacerbating
chronic conditions like asthma and COPD, and landing you in the hospital with
pneumonia.
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| Must wash hands... Must wash hands... Must wash hands... |
But researchers are fighting back by trying to create a vaccine for the common cold. Sounds simple, right? I mean we have vaccines for practically
everything else, so you are probably asking yourself, why don’t we have one
that works against colds? There are
actually a few good reasons we don’t yet have one.
First of all, the common
cold is caused by a few different types of viruses, including but not limited
to rhinoviruses (the focus of this post), coronaviruses, adenoviruses, and respiratory syncytial virus, among others. Among the
rhinoviruses alone, there are 3 species (‘A’, ‘B’ and ‘C’) encompassing about
150-170 different strains that you can become infected with! We call these different strains
‘serotypes’. That is a lot of different viruses to vaccinate against.
Many of the established vaccines
that we receive protect against a single serotype of a particular
virus (ex the measles vaccine), or just a small number of serotypes (like the oral
poliovirus vaccine, which protects against all three serotypes of poliovirus). But the newer pneumococcal vaccine protects against 23 serotypes of virus! Vaccines that are able to
protect against multiple strains of a virus are called polyvalent vaccines, and researchers from Emory University School
of Medicine in Atlanta, Georgia, are trying to create a polyvalent vaccine that
would protect us against as many strains of the rhinovirus as possible.
On the most recent episode of
‘Audiommunity’ (Episode 27- Macaque PrisonGangs) we discussed a paper from this group at Emory entitled “A polyvalent
inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques”, which
was recently published in the journal Nature (read the original paper here). To briefly summarize the work, the
researchers made polyvalent rhinovirus vaccines by simply combining several
serotypes of rhinovirus together into a vaccine cocktail, and inactivating them
(so this is a “dead” vaccine, no live virus).
They then tested whether or not the cocktails could produce an immune
response in mice, and later, in rhesus macaques.
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| Different serotypes are mixed and inactivated with formalin |
The way they tested the
immune response to the vaccine was by injecting it into mice and then taking a
sample of the mouse serum and looking for “neutralizing antibodies”, against
each of the strains of rhinovirus in the vaccine. Neutralizing antibodies are proteins that are
made by our B cells that are designed to recognize an “intruder” (in this case,
the dead viruses in the vaccine), bind to it, and “neutralize” its biological
effects. A good vaccine should induce a
broad neutralizing antibody response, meaning that a lot of neutralizing
antibodies should be generated that recognize a lot of different parts of the
“intruder”.
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| Mouse is injected, serum is collected, and neutralizing antibodies measured |
What they found was that as
long as the input amount of viruses in the cocktail was high enough (we call
this the viral titer), they could get a decent immune response to the vaccine
no matter how many viruses they added to it (they tested 10-, 25-, and
50-valent vaccines in this paper).
Historically, two, 10-valent rhinovirus vaccines were tested in the
seventies that generated only a poor responses in test subjects (something like
only 30-40% of them). However, these
vaccines had really low input virus titers that were further diluted when made
into one-milliliter vaccine doses. The
researchers in this study recreated those vaccines using higher input virus titers,
and were able to improve the neutralizing antibody response significantly over
that of the original low titer vaccines.
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| The higher the input titer, the better the neutralizing antibody levels (inset: think of titer as concentration of viruses) |
They went on to test a
25-valent and a 50-valent vaccine in rhesus macaques, which are a nonhuman
primate common in medical research.
Remarkably, they were able to detect high levels of neutralizing
antibodies against 100% of the rhinovirus serotypes in the 25-valent vaccine,
and against 98% of the serotypes in the 50-valent vaccine! This is good news for humans, since the more
serotypes we can squeeze into the vaccine, the lower our chances of getting
sick become.
However, there are a few minor drawbacks to this work. The researchers found that the neutralizing
antibody response is serotype-specific; there is no
cross-neutralization against other viral strains not a part of a particular
vaccine. This means that an antibody against
one serotype of rhinovirus is not protective against a different serotype of
rhinovirus, so any serotypes not represented in a vaccine are still capable of infecting you and making you ill.
Another issue is that there were no challenge experiments in this
study. The reason for this is that there
are no animal models for the common cold (you can only recapitulate some of the
pathology in mice and rhesus macaques), so there is no way of knowing from this
study whether these vaccines will actually prevent you from getting sick. But this shouldn’t be too difficult to test
in a clinical trial in human subjects since cold viruses aren’t all that
pathogenic.
But perhaps the biggest
drawback to this work is that the researchers only tested polyvalent vaccines
against the ‘A’ species of rhinovirus.
Rhinovirus A accounts for about 83 strains of virus; but B accounts for
32, and the newly discovered ‘C’ species accounts for 55 strains, which is not a
small number of viruses, all vying to infect us. The problem is that the ‘C’ species viruses
are really hard to grow in cell culture.
And as this study showed, the success of the vaccine is all about
getting nice, high, input virus titers.
So in the meantime, researchers are working on figuring out the best
ways to grow these strains so they can add them into the vaccine
cocktails.
Emory has optioned the
vaccine technology to a startup company called MeissaVaccines, Inc. They have just
received an SBIR (small business innovation research) grant from the National
Institutes of Health to develop an 83-valent human vaccine, so let’s wish them luck
in their efforts to make the common cold a thing of the past! I, for one, will happily volunteer as a human
test subject!
