We will now walk through three case
studies of biodefense vaccines.
The first one will take us through
over 300 years of medical history
with the advent of variolation
to prevent smallpox.
The second study deals with
the use of the FDA animal
rule to expand the indication of
BioThrax, the anthrax vaccine,
from pre-exposure to
And lastly, we will cover a more
recent event that has mobilized
the biomedical community in
ways that we've never witnessed
before, the Ebola outbreak.
Let's begin with smallpox.
Smallpox is believed to have killed
more people than all wars combined.
It has devastated
mankind for centuries.
We are, indeed, fortunate
for the work of Edward Jenner
and the many scientists
that worked towards the ultimate
eradication of this scourge
Along with rinderpest, a
disease of ruminants, smallpox
is the only other disease
eradicated from this planet.
But long before Edward Jenner
discovered the protective effects
of cowpox by observing that milk
maids rarely developed smallpox,
people had been using variolation to
protect against smallpox infection.
However, the observation that cowpox
could also protect against smallpox
and that it was much
safer to use renders
Jenner's observation one
of the most important
medical discoveries of all time.
Shown here is Dr. Jenner vaccinating
eight-year-old James Phipps on May
14, 1796 with the material he
obtained from cowpox lesions
on the hands of the young
dairy maid, Sarah Nelmes.
Two months after the boy
was vaccinated with cowpox,
Jenner challenged him with matter
from a fresh smallpox lesion.
Mind you, this was well before the
days of informed consent and INDs.
Fortunately, the boy did
not develop smallpox,
and Jenner rightly concluded
that cowpox protected
against smallpox infection.
But smallpox continued to be a
scourge on humanity for centuries
thereafter, until a hemisphere-wide
effort began in the 1950s
by the Pan American
Most of the smallpox vaccine that
was produced during this period
was derived from vaccine grown
on the skin of live calves.
During the eradication period,
the World Health Organization
called upon Wyeth, the company that
had been manufacturing smallpox
vaccine since the late 19th
century, to not only continue
to manufacture this vaccine but also
develop a better injection system.
This led to the discovery
and the implementation
of the bifurcated needle and the
eventual eradication of smallpox.
Dryvax, the Wyeth vaccine, is a
live virus preparation of vaccinia
virus prepared from calf lymphs.
It was a highly-effective vaccine,
but with serious adverse events
in 1% to 2% of all vaccinees.
After the WHO declared smallpox
eradicated, Wyeth discontinued
It wasn't until 2001, after the
attacks on the World Trade Center
and Pentagon and the subsequent
anthrax letters, that a smallpox
vaccine was deemed necessary.
At the time, it was believed that
after the collapse of the Soviet
Union smallpox may have become
available to other countries
or terrorist groups.
Moreover, since vaccinations
had been halted in the US
in the late 1960s, over
half of the population
was susceptible to smallpox.
A major effort was taken to
resuscitate the smallpox vaccine.
ACAM2000 was derived by
a small biotech company
by the name of Acambis.
It was eventually bought
by Sanofi Pasteur.
ACAM2000 is a clonal
isolate from Dryvax.
Dryvax is a vaccine composed
of many different variants
of vaccinia virus.
ACAM2000 is a clonal isolate,
grown in defined vero cell culture.
ACAM2000 was approved
by the FDA in 2007
and has been stockpiled by
the US government ever since.
It is routinely used
to vaccinate laboratory
workers and military personnel who
may be at high risk for exposure.
It is administered by scarification
using bifurcated needles, just
But like Dryvax, it also adds to
the potential for transmission
to close contacts of vaccinees.
Several cases of contact
vaccinia have been documented
in adults and infants
living in households
of vaccinated military personnel.
And unexpectedly, a high
incidence of miopericarditis
also was reported in clinical
trials and in military personnel
during ACAM2000's implementation.
As a result, the FDA placed what
is known as a black box warning
on the label of ACAM2000, indicating
that the product carries with it
a significant risk
for adverse effects.
One of the phase IV
commitments for this product
is to continue monitoring
cardiac events in all vaccinees.
The time the US government realized
that although ACAM2000 can be
an effective vaccine to
protect the general population,
there could be risks during
a mass vaccination campaign,
especially in immunocompromised
and HIV-infected individuals.