Vaccines in general, are the best tool for
prevention against any infectious disease.
And for them to be effective and to be accepted,
as being effective and
again this is any infection,
it should be at least 50% effective.
Specific to COVID-19 and the
SARS-Coronavirus II vaccines,
the initial requirements in the United States,
were that the new vaccine products,
be at least 50 % effective.
Now, as we are moving forward into the current,
there are many vaccine products,
including a vaccine product,
which has been tested and
found to be safe and effective
in children from ages 12 years of age and up.
This is the Pfizer messenger RNA vaccine,
which showed 100 % efficacy against COVID-19,
in this young age group.
So, vaccines are always the best
tool for prevention as noted
and luckily, the COVID-19 pandemic,
has triggered creation of
very successful vaccines,
even when compared to the influenza vaccine,
which is perhaps one of the most common
and upheld successful interventions.
The influenza vaccine, typically 40%
to 60% effective in any epidemic year,
but, it is still quite useful
in preventing severe disease
and preventing an overburdening
of the healthcare system.
Full vaccines then, are recommended for everybody,
including those who have had prior COVID-19,
since it has been demonstrated
that patients with mild
to even moderate COVID-19, have
a risk of second infections
or even third infections and
vaccines provide a robust,
high level of antibody protection
against currently the spike protein,
which is, quite protective even for
those who have had prior infection.
So, at least in the States
the CDC recommends vaccines,
for all individuals despite
their prior infection status.
However, full vaccination
meaning a full either two doses,
for a two dose vaccine,
or one dose for the Johnson Johnson vaccine,
which is a one dose vaccine,
but full vaccines remain controversial.
Again, it is unclear exactly
whether a previously infected person
requires just one dose of
vaccine to get robust protection
or whether having the two doses,
will provide long-lasting and robust protection.
So, as of the time of this this lecture,
that issue remains unresolved,
but currently at least
individuals previously infected,
do require vaccine of some sort.
What are the types of vaccine methodologies?
And we start with the products by
AstraZeneca and Johnson and Johnson,
similarly, Russia’s products Sputnik V,
follows this methodology as well,
these are vaccines which include a
non-replicating adenovirus as the vector
or the carrier for a gene encoding the
spike protein of SARS-Coronavirus II.
The next category are the vaccines
made by Pfizer and Moderna.
These are messenger RNA vaccines in which,
the messenger RNA, specifically
and only for the S-protein gene,
are included in a nanoparticle
encapsulated lipid particle construct,
which then, triggers immune reaction.
And then a vaccine produced by Novavax,
takes the actual spike
protein itself the S1-protein,
coats it with synthetic nanoparticles
and then provides it in an
immune boosting adjuvant,
which triggers immune reaction.
So, in general, how do vaccines work?
Well, we know that vaccines work by triggering,
a specific adaptive immune response,
by the human immune system,
which then, creates memory,
so, that the individual's immune system,
can react to subsequent challenge,
by that same antigenic challenge.
Looking specifically at the
messenger RNA based vaccines
and this this is newer technology to most of us,
it is really quite unique and
exciting as a platform for vaccines,
because this process will work for
other infectious diseases as well.
In a messenger RNA based vaccine
against SARS-Coronavirus II,
the messenger RNA code for the
spike protein the S1-protein gene,
is introduced into the human body,
where, it is taken up or absorbed
by antigen presenting cells,
as with any other antigen delivery via vaccine.
However, those antigen presenting cells,
as they ingest the messenger RNA,
then go through translation
and transcription processes,
to create the spike protein and
then express the spike protein,
at their cell surface along
with MAC classes 1 and 2
and or, release the spike protein
where it is then able to be ingested
and to trigger an immune response,
by other antigen presenting cells.
So, here, we see the delivery vehicle,
the messenger RNA vaccine,
with the messenger RNA code,
for the spike protein in its little nanoparticles,
it then is taken up as the full
construct by the anti-presenting cell,
the messenger RNA is introduced
into the anti-presenting cell,
where, it is translated into spike protein,
the spike protein then is
expressed at the cell surface,
with MAC class 1 and 2 to
T-lymphocytes and B-lymphocytes,
which, are the next stage
and or secreted externally
to where it is then taken up by other
antidepressant cells in the same process
and that then drives the adaptive
immune response using T-lymphocytes
the CD4+ T-helper T-lymphocytes
and B-lymphocytes to create
So, that is the strategy, does it work?
Now, this this is a historic slide,
but it shows in the United States,
the most recent surge or peak,
which occurred in the winter
of 2021, in the States
and you can see on the slider front of you,
around, I guess it was December, is when,w
max vaccinations started in the United States
and it took quite some time of course,
to get to anything resembling
a decent vaccine coverage
and in fact, currently the
United States in general,
is hovering around, 50% maybe
54% total fully vaccinated
and just a little bit more who
have received at least one dose.
However, as that vaccine coverage has rolled out,
one can see a decrease in the
number of cases quite robustly,
as we go into spring of 2021.
So, that would suggest that the
vaccine efficacy was excellent.
What is vaccine efficacy?
It is, the degree to which a vaccine prevents
disease and potentially also transmission,
so, preventing infectivity is important,
under ideal or controlled circumstances.
Typically, one creates an estimate
of the efficacy of any intervention,
whether it's in this case a vaccine
or medication or something similar,
by comparing that that test
group, the vaccinated group,
with a placebo group,
so, efficacy is how well it prevents disease
and potentially transmission disease.
That's what's predicted in a
or a can a clinical study in
which everything is controlled.
What about real world or population level data?
This is what is known as
the effectiveness estimate.
This is how well in this case the vaccine
actually performs in the real world.
As you would imagine,
that the real world numbers are going to be lower
than the carefully controlled efficacy numbers.
But that's okay, as long as
the effectiveness is adequate.
What one is really looking for of course, is,
how effective is the intervention
the vaccine against infection?
does it do its job in the real world setting
and this is the number the
effectiveness against infection,
that the FDA signed, an a hoped for value of 50%.
As it turns out that that target
was exceeded significantly,
by most vaccine products currently available,
in the United States and Europe
and even parts of India and Africa.
So, most vaccines are up to 90%
effective against symptomatic infection,
so, that is fantastic.
And of course, on a personal level
one wants a product a vaccine which
will protect one from infection period.
However, in terms of major use of resources,
the absolute morbidity, the challenge
that all countries have faced,
in the COVID-19 pandemic,
has been the burden on health care infrastructure,
so, what one really wants
to prevent that challenge,
is, effectiveness against severe disease.
How well does the vaccine do against a disease,
which requires, the patient to be hospitalized
and to consume health care resources
and of course, this is the most important factor,
not just to prevent death, which is ideal,
but also prevent use of the healthcare system.
And again, major vaccines,
certainly the messenger RNA vaccines
and several of the adenovirus vector vaccines,
are near or at 100% effectiveness
against severe disease, that's fantastic.
Okay, let's fast forward into
the real world, one more step
and that is knowing that as we attempt
to control, the SARS-Coronavirus II
in nature, nature abhors
a vacuum and new variants,
mutations are occurring all the time.
How well do the vaccines do,
in effectiveness against the new virus variants?
And especially the delta variant
which is the current challenge,
being faced by the United States.
Yes, there are variations in effectiveness,
but in general, the currently
available vaccines worldwide,
remain effective against
the new variants of concern,
that have been identified to this point.
Most of the vaccines do
better against severe disease,
even against the variants,
but all of them have at least some protection,
even as low as 50% against
the new variance of concern.
As we speak, however, surveillance
on goes all across the world
and new vaccines are still in development,
so, any slide regarding this
is likely going to be dated,
by the time you're watching it.
Now, vaccines are fantastic, but
they are also an intervention,
a medical science intervention
and so there will be side effects,
most of which are minor.
So, the minor side effects identified
with the vaccines noted so far,
are, a flu-like illness, so soreness
at the injection site of course,
which, will last a couple days to a week
and accompanied sometimes by malaise,
low-grade fevers, some sore muscles
and that basically reflects a
very excellent immune response,
by the vaccine recipients.
Thankfully, major side effects
and certainly fatal side effects
have been incredibly rare,
that's a wonderful thing and that
of course then drives the question,
was that incredibly rare, “I
hadn't seen it before side effect,”
in my single vaccine
recipient, due to the vaccine,
or was it something related to health issues,
pre-existing in the vaccine recipient
and in many cases it's very difficult to tell,
as proof of causality is difficult to achieve.
So, as an example there have been
evidence episodes of myocarditis,
in vaccine recipients of one
of the messenger RNA vaccines,
Pfizer or Moderna, mostly young men
and those incidence, numbers of myocarditis,
in those individuals have exceeded
the rate normally witnessed,
in a non-vaccine, non-covid pandemic time.
So, that would suggest that
there is some association,
why we don't know, but some association,
with messenger RNA vaccination and
myocarditis, in certain individuals.
So, what are the side
effects that we've witnessed,
anaphylaxis, of course, would
be a severe side effect,
anaphylaxis is possible with any vaccine.
Fortunately, for the messenger RNA vaccines,
in which some episodes have been reported,
this is an incredibly low incident,
so just 3 to 5 per million vaccine recipients,
mostly in women who had pre-existing
severe environmental allergies
or allergies to food or other products.
The incidence of thrombosis and thrombocytopenia
and specifically, a heparin induced
or vaccine-induced immune thrombocytopenia,
has been demonstrated in patients who received one
of the adenovirus vectored
vaccines mostly AstraZeneca
and Johnson and Johnson.
These individuals, have had some
significant effects of this thrombosis,
including cerebral venous thrombosis
and splanchnic vein thrombosis,
are the two most common, thrombotic
illnesses witnessed in these individuals.
With the AstraZeneca vaccine, out
of 34 million doses administered,
you can see the numbers there, just 169
episodes of cerebral venous thrombosis
and 53 episodes of splanchnic vein
thrombosis, have been demonstrated
and confirmed with 18 deaths and based on that,
although it is an incredibly rare
risk, but the risk is felt to be real.
So, in many countries, AstraZeneca,
is not given to vaccine recipients,
who are under age 60,
because these cerebral venous
and splanchnic venous thrombotic events,
all occurred in young adults.
In the Johnson and Johnson vaccine,
out of 20 million doses administered,
25 cases and 9 deaths respectively,
with vaccine associated
So, if we then try and compare
the risk of vaccine effects,
whether they're minor or major or severe or fatal,
to other adverse effects, these are
great these are great talking points,
if one is having this
conversation with one's patients,
the lifetime chance of dying
in a motor vehicle accident,
1 in 103 that's huge.
The lifetime chance of getting struck by
lightning 1 in 15,300 and 10% of those die.
So, one is absolutely going to be
encountering a lot of vaccine hesitancy,
due to the side effects, but the risks of
death from COVID-19 itself, are far greater,
than any theoretical risk from vaccine
and one can also use these lifetime risks as well.
So, how long will the protective effect last?
Well, that's not known, in fact
there are many questions that emerge,
as we go further into the pandemic
and here are some of the ones to
which we don't yet have answers.
It appears, that vaccine
recipients in the vaccine trials,
have had protective immune response,
for a minimum of one year after vaccine,
but that number will continue to lengthen
as we go further into the pandemic.
Can the vaccines prevent asymptomatic infection
or can they prevent transmission?
The tentative answer so far is, yes,
but how successfully remains to be determined.
Will they prevent infection by all
the current or emergent strains?
To date, the answer is, yes,
but would decrease efficacy
compared to the original strain.
Will they be effective in
Here the data would suggest
that immunocompromised patients
are not all created equal,
those who are on immunomodulatory
drugs for example,
somebody with systemic lupus or
erythematosus or rheumatoid arthritis
on a biologic agent, still have a robust response,
while a solid organ transplant recipient
or a chemotherapy recipient does not,
so, it's a variable response and there may
be a need for booster in those patients.
Will the vaccines be effective in patients,
who are at high risk for severe
COVID-19 as those who are at low risk?
Again, the answer would suggest, yes,
but this is a smaller more
difficult to study population,
because of complications from
those same comorbidities, which,
already lend to morbidity and mortality.
So, what are the major concerns
with vaccine strategies?
Perhaps, the hugest one is
getting vaccines delivered,
to as many people in the world as is possible
and of course, there are many countries
that are horribly under-resourced
and either have no vaccine doses whatsoever
or have been able to immunize less
than 1% of that country's population.
So, making vaccines available to all countries,
all people in the world, as soon
as possible is a critical concern,
if we have and wish to have any chance
of getting through this pandemic.
Protecting those who are at
highest risk for severe disease
or those for whom the risk
of infection is significant.
So, protecting healthcare workers,
so, that we can continue to care
for those who do have COVID-19.
Protecting the elderly,
the ones who are at highest risk
of hospitalization and death
and including those who have immunodeficiency
and then represent a huge burden
in healthcare infrastructure.
What about the variance?
So, following the impact of the
mutant variants of the virus
and adapting our vaccine
strategies to reflect those,
all these are our major concerns and
especially the duration of immunity.
How do we detect if the vaccines
are successful and for how long?
Is it simply checking antibodies?
or should we look at T-cell function,
should we look at plasma cell
derivations populations and lineages
of COVID-19 effective plasma cells
or neutralizing antibodies,
versus other antibodies.
So, there are a whole bunch of concerns
which remain to be fleshed out.
And then finally, limiting the insertion
of the actual SARS-Coronavirus II,
into the viral milieu of
humans in an endemic matter.
What does this mean?
At some point in time, way, way, way,
back when influenza was also a pandemic,
however, it was so successful,
that it entered human infectious milieu
and now creates an annual epidemic.
The fears are that our point of no return for,
SARS-Coronavirus II has already been crossed
and that we will likely have seasonal recurrences,
just like we do with influenza,
which, will require an annual booster vaccine.
That is absolutely, I think a likely reality,
if not already a true reality.
And then what are the long-term
complications of the disease?
For example, those individuals
who are long COVID-19 survivors,
the long haulers as they've been called,
which has horrible and tremendous
impact on quality of life,
can those be prevented by COVID-19 vaccination
and can those be addressed as we
bring this pandemic under control?
So, lots yet to be determined,
the science of course is evolving
at a rapid pace in this pandemic
and that is a good thing,
because otherwise nature in
its abhorrence of a vacuum,
will continue to win,
in creating variance,
which, will eventually be the death of us.