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| DATE | 2021-02-02 |
| FROM | Ruben Safir
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| SUBJECT | Subject: [Hangout - NYLXS] Run Down of Vaccines from the BBC
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BTW - the Russian Vaccine has been shown to be very good..
https://www.bbc.com/future/article/20210114-covid-19-how-effective-is-a-single-vaccine-dose
How effective is a single vaccine dose against Covid-19?
(Image credit: Getty Images)
A scientist holding up a vial of Covid-19 vaccine (Credit: Getty Images)
By Zaria Gorvett
14th January 2021
Pretend it didn't happen expert advice on how to behave after
receiving a single dose of any of the Covid-19 vaccines.
T
The cases are already beginning to emerge.
When 85-year-old Colin Horseman was admitted to Doncaster Royal
Infirmary in late December, it was for a suspected kidney infection. But
not long afterwards he caught Covid-19 at the time, roughly one in
four people in hospital with the virus had acquired it there. He
developed severe symptoms and was eventually put on a ventilator. A few
days later, he died.
At first glance, Horseman's situation may seem fairly typical, though no
less tragic for it. After all, at least 84,767 people have now succumbed
to the disease in the UK alone at the time of writing. But, as his son
recently explained in a local newspaper, less than three weeks earlier
he had been among the first people in the world to receive the initial
dose of a Covid-19 vaccine the Pfizer-BioNTech version. He was due to
receive the second dose two days prior to his death.
In fact, most vaccines require booster doses to work.
Take the MMR measles, mumps and rubella vaccine, which is given to
babies around the world to prevent these deadly childhood infections.
Around 40% of people who have received just one dose are not protected
from all three viruses, compared to 4% of those who have had their
second. People in the former group are four times more likely to catch
measles than those in the latter and there have been outbreaks in
places where a high proportion of people have not completed the full MMR
vaccination schedule.
"The reason that people are so keen on boosters and consider them so
vital is that they kind of send you into this whole other kind of
fine-tuning mode of your immune response," says Danny Altmann, professor
of immunology at Imperial College London.
How booster vaccines work
When the immune system first encounters a vaccine, it activates two
important types of white blood cell. First up are the plasma B cells,
which primarily focus on making antibodies. Unfortunately, this cell
type is short-lived, so although your body might be swimming in
antibodies within just a few weeks, without the second shot this is
often followed by a rapid decline.
Then there are the T cells, each of which is specifically tailored to
identify a particular pathogen and kill it. Some of these, memory T
cells, are able to linger in the body for decades until they stumble
upon their target meaning immunity from vaccines or infections can
sometimes last a lifetime. But crucially, you usually won't have many of
this cell type until the second meeting.
The booster dose is a way of re-exposing the body to the antigens the
molecules on pathogens that trigger the immune system to initiate part
two of the response. "You've kicked in all this fancy stuff," says
Altmann. "So, once you've had your boost you'll have a higher frequency
of memory T cells and ditto to some extent for the size of the pool of
memory B cells you'll have. They'll also be making higher quality
antibodies."
On second exposure to the same vaccine or pathogen, the B cells that
remain from before are able to rapidly divide and create a menacing
throng of descendants, leading to a second spike in the amount of
antibodies circulating.
Manufacturing enough of each of the vaccines will take time, so some
countries such as the UK have decided to delay the second dose
(Credit: Alamy)
Manufacturing enough of each of the vaccines will take time, so some
countries such as the UK have decided to delay the second dose
(Credit: Alamy)
The second dose also initiates the process of "B cell maturation", which
involves selecting the immature ones with the best receptors for binding
to a particular pathogen. This happens while they're still in the bone
marrow where white blood cells are made and afterwards they travel
to the spleen to finish developing. This means B cells are not only more
numerous afterwards, but the antibodies they produce are better targeted.
You might also be interested in:
Here's why vaccination beats infection
The quest to make a global vaccine in 12 months
How Covid-19 is changing the flu
Memory T cells, meanwhile, also proliferate rapidly. They're already
thought to have played a critical role during the current pandemic,
protecting some people from developing severe Covid-19. Though the virus
may have only been circulating globally since around December 2019,
there's some evidence they may have "seen" other coronaviruses before,
such as those that cause the common cold allowing them to recognise
Covid-19.
So how effective is a single dose of each of the Covid-19 vaccines?
At a time when the answer is more urgent than ever especially as the
British government has decided to delay the second dose of all currently
approved Covid-19 vaccines from 3-4 weeks to 12, and Russia is trialling
a single-dose regimen of its Sputnik V vaccine named "Sputnik-Light"
it's also surprisingly complicated. Here's what we know so far.
Pfizer-BioNTech
According to Pfizer data published in December 2020, the Pfizer-BioNTech
vaccine is roughly 52% effective after the first dose. Out of 36,523
participants in the phase three trial the final stage of testing where
people either received two full doses, 21 days apart, or a placebo who
had no evidence of existing infection, 82 people in the placebo group
and 39 in the vaccine group developed Covid-19 symptoms.
Preclinical trials would have shown that they didn't think there was
enough immunity after one shot. So they've gone for both Deborah
Dunn-Walters
However, this early protection comes with some important caveats. First,
the protection doesn't kick in until at least day 12 until then, there
was no difference between the two groups. Secondly, one dose is still
significantly less protective than two. The latter is 95% effective at
preventing the disease after a week.
But there is also another figure that has been circulating on the
internet, and anecdotally, being fed to patients by certain doctors
the suggestion that the first dose is around 90% effective. And this is
where it gets a little more complicated.
The second estimate comes from the UK's Vaccine Committee, the JCVI, who
decided to calculate the efficacy of the vaccine differently. Instead of
using all the data on the number of infections, including from days when
the first dose hadn't yet started to work, they only looked at days
15-21. Using this method, the efficacy of the vaccine jumps up to 89%,
because it's not being diluted by the relatively high number of
infections before the vaccine begins to have an effect. Taking things
even further and only looking at the first seven days after the second
dose (days 21-28) because the second dose might not have kicked in yet
by then it's 92%.
However, these calculations are controversial.
A vaccine developed to fight Ebola is the only one that uses the same
technology as the Russian and Oxford-AstraZeneca Covid-19 jabs (Credit:
Getty Images)
A vaccine developed to fight Ebola is the only one that uses the same
technology as the Russian and Oxford-AstraZeneca Covid-19 jabs (Credit:
Getty Images)
"People are very keen on at the moment on that graph in the Pfizer paper
in the New England Journal of Medicine where they show that there must
be some kind of de facto benefit as early as something like day 14,"
says Altmann. "It's the one where the curve for the placebo group and
the vaccine group completely diverge, and cases start taking off in the
placebo group. But obviously that's not measuring an immune response
directly it's using quite a crude measure of how many people have been
infected." Altmann explains that he wouldn't advise anyone to consider
themself safe 14 days after their first dose of the vaccine. "The graph
is just a way of saying 'something is happening'," he says.
In a more recent development, an Israeli academic who coordinated the
countrys Covid-19 response Professor Nachman Ash has claimed that a
single dose of the vaccine is not as effective as Pfizer originally
estimated. However, the comments have been widely criticised.
There are a number of reasons that it is inappropriate to compare the
research, which was conducted by the health organisation Clalit, with
the Pfizer study. For one, the Israeli study found that a single dose of
the vaccine reduced the number of people testing positive for the virus,
i.e. being infected, by 33%, while the Pfizer paper suggested that it
would prevent 52% from developing symptoms they looked at two
different things.
In addition, the data from Clalit has not been made available, or
peer-reviewed. It also involved examining the impact of the vaccine just
two weeks after people had received it considered too early to see an
immune response rather than three, as in the Pfizer study. Finally,
the research was not a clinical trial, but rather an observational
study, which means the results should be viewed with caution.
Oxford-AstraZeneca
For the Oxford-AstraZeneca vaccine, things are a bit different. In a
paper published in January, the authors explain that the vaccine offers
protection of 64.1% after at least one standard dose. This compares to
70.4% if you've had two full doses, or oddly 90% in people who have
had one half dose followed by one full dose.
Meanwhile, based on these unpublished data they have seen, the Vaccine
Committee has estimated that, from three weeks until 9-12 weeks after
the first injection, the vaccine prevents around 70% of cases of serious
disease.
Because the phase three trial included two gaps between the first and
the second dose including one of six weeks and a longer one of 12
weeks it's possible to say with more certainty that the first dose can
continue to provide some protection for at least a few months before the
booster shot.
Moderna
According to a document the company submitted to the FDA, the Moderna
vaccine can provide 80.2% protection after one dose, compared to 95.6%
after the second (in people aged 18 to 65 it's 86.4% in those over
65). As with the Pfizer vaccine, all participants in the phase three
trial received two doses of the vaccine or a placebo within a single set
time period in this case, 28 days so it's not yet known whether the
immunity from a single vaccine would continue, or drop off after this stage.
Sinovac
The CoronaVac vaccine was developed by Sinovac, a biopharmaceutical
company based in Beijing, China. This version is unusual as it has been
trialled independently in several countries all of which have produced
different results.
According to researchers in Turkey, the vaccine is 91.25% protective,
while scientists in Indonesia have said that its 65.3% effective, and
the Butantan Institute in Sγo Paulo, Brazil recently announced that the
vaccine prevents 50.4% of people from developing symptoms. At the
moment, no one has released data on the efficacy of a single dose
these figures only apply to two doses, spaced 14 days apart.
The results have been viewed with some scepticism, because they were
published via press releases, instead of as would normally be the case
in a peer-reviewed journal. Without access to more information about
the trial methods and the data that was collected, its harder for
scientists to make their own assessments of the results' validity.
Sinopharm
In all, there are five Chinese vaccines at various stages of development.
Another is "BBIBP-CorV", by the state-owned company Sinopharm, based in
Shanghai. Officials in the country recently announced that this version
is 79% effective after two doses though by then, it had already been
distributed to nearly a million people. This estimate has not been
verified by the international community, because the underlying data and
methods for its trial have not been made publicly available. It's not
yet clear how protective it might be after a single dose.
Outside China, the vaccine is currently being tested all over the world,
and has been approved in Bahrain, Egypt, Jordan, the Seychelles, and the
United Arab Emirates. The UAE recently became the first to rate its
efficacy, claiming via a press release that it is 86% effective.
Most of the Covid-19 vaccines that have been developed target the "spike
protein" on the virus' surface (Credit: Getty Images)
Most of the Covid-19 vaccines that have been developed target the "spike
protein" on the virus' surface (Credit: Getty Images)
Sputnik V
The Sputnik V vaccine is named after the world's first artificial
satellite, the iconic Soviet-era "Sputnik 1", which was launched into
low Earth orbit in October 1957 it burned up three months later when
its batteries died. Its namesake was developed by the Gamaleya Research
Institute of Epidemiology and Microbiology in Moscow, Russia.
As with the others, this vaccine is administered as two doses, and is
apparently 91.4% effective after both there is currently no publicly
available information on the efficacy of just one dose.
Again, these results havent been published in a peer-reviewed journal
and therefore may not be reliable. Despite a rapid rise in the number of
Covid-19 cases in the country, the vaccines safety and efficacy has
been viewed with suspicion by many Russians, according to a report in
the Washington Post. In the first week it was rolled out in December,
clinic waiting rooms were reportedly half-empty.
More recently, the Russian government announced that it was developing a
new version, "Sputnik-Light", as a temporary solution to shortages of
the original. The vaccine would be delivered as a single dose, though
it's not yet clear how protective it would be.
Can you change your behaviour after receiving a single dose?
"I would behave exactly as if I hadn't had the vaccine yet," says
Altmann. "I wouldn't drop my guard at all or do anything differently."
Deborah Dunn-Walters, professor of immunology at the University of
Surrey, is just as unequivocal about how people should behave. "There's
a couple of reasons for that," she says. "One is, you're not going to be
fully protected. And another is there is no evidence as yet that having
had the vaccine will stop you getting the virus and passing it on."
Dunn-Walters explains that the efficacy of the vaccines were largely
assessed by looking at whether they prevented people from developing
symptoms not if they stopped them being infected with the virus. "And
we do know that it's possible to have asymptomatic infection," she says.
There is not yet any evidence that one dose or even two of the
existing vaccines will stop people from giving the virus to others.
Can you skip the second vaccine dose?
"Preclinical trials would have shown that they didn't think there was
enough immunity after one shot. So they've gone for both," says
Dunn-Walters. Similarly, during phase three trials, there were more
antibodies and T cells in the blood after two doses than there were
after one.
Immunity can take weeks to emerge, so Covid-19 vaccines can't protect
you immediately (Credit: Getty Images)
Immunity can take weeks to emerge, so Covid-19 vaccines can't protect
you immediately (Credit: Getty Images)
As the chief executive of Pfizer, Albert Bourla, explained in December
that it would be a "big mistake" to skip the second dose, because it
almost doubles the amount of protection you get.
Pfizer and BioNTech themselves have already urged caution on the grounds
that their data ends at day 21, and "there is no data to demonstrate
that protection after the first dose is sustained after 21 days". It's
possible that the protection people seem to have will suddenly drop off
after that point in fact, this wouldn't be surprising based on the way
the immune system usually works.
Reliably estimating how long the protection from a single dose might
last is further complicated by the fact that all the currently approved
Covid-19 vaccines are using brand-new technology.
The Oxford-AstraZeneca and Sputnik-V vaccines both involve modified
versions of adenoviruses a group that can break into many different
cell types and cause a range of illnesses, such as respiratory
infections. While the Oxford version uses an adenovirus from
chimpanzees, the Russian one includes a mixture of two human types.
The virus was altered for the vaccines so that it's safe and can't make
more copies of itself inside cells. It is able to teach the body to
recognise the coronavirus by encoding the instructions to make a feature
found on its surface, the spike protein.
Though adenoviruses have been used in cancer vaccines and gene therapy
for years, they had only ever been used once before to prevent a viral
infection an Ebola vaccine using this method was approved for use in
European Union countries in July 2020.
It's not yet clear how long the partial protection provided by a single
dose of any of the Covid-19 vaccines will last (Credit: Getty Images)
It's not yet clear how long the partial protection provided by a single
dose of any of the Covid-19 vaccines will last (Credit: Getty Images)
The Moderna and Pfizer-BioNTech versions, on the other hand, are
arguably even more pioneering. Both contain countless miniscule
fragments of mRNA, which as with the adenovirus-based vaccine encode
the spike protein from the surface of Covid-19. They are the only mRNA
vaccines to have ever been approved for use in humans.
Without other mRNA vaccines to compare them to, the world is in
uncharted territory. As Ronald Corley, professor of microbiology at
Boston University, recently explained in an interview with the
university news magazine, there are many unknowns, such as whether they
will work just as well in people from different ethnicities, and how
long immunity will last.
The Sinovac and Sinopharm versions contain inactivated coronavirus
particles instead. This method is less unusual the concept of using
dead pathogens in vaccines has been around since the late 19th century.
However, its no less clear how long the immunity will last, since no
vaccines made from a member of this virus family had ever been approved
before the pandemic.
Immunity takes time to develop
Finally, Dunn-Walters is keen to point out that immunity takes time to
develop so regardless of whether a single dose of any of the Covid-19
vaccines can provide protection eventually, for the first couple of
weeks you will have no more than you started with.
"There's a part of the immune system which we call innate immunity,
which responds immediately," says Dunn-Walters. This encompasses
physical barriers to infection, like your skin, as well as certain types
of white blood cell and chemical signals. But she explains that this
generally can't prevent disease on its own and isn't affected by
vaccines. "So you need adaptive immunity as well. But the issue with
adaptive immunity is that, as its name says, it's adaptive it adapts
to individual challenges by pathogens."
For vaccines to have any effect, they must encourage the body to make
more immune cells some of which in turn produce antibodies. "And this
takes time," says Dunn-Walters.
So while the global roll-out of the new vaccines may be exciting, it
looks like most of us will have to wait a while longer before normal
life can resume.
--
This story was updated on 18/1/2021. An earlier version incorrectly
stated that an Ebola vaccine using adenoviruses had been approved for
use in the US. Separately, it said that the CoronaVac vaccine was tested
by the UAE. The Ebola vaccine has been approved for use in the European
Union and the UAE tested a different vaccine, made by the company
Sinovac. The article has been corrected to reflect this.
--
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