158
Cytomegalovirus and Varicella–zoster Virus Vaccines
Tab. 1
Important events in the history of varicella vaccine.
Year
Event
1974
Development of live-attenuated Oka-strain vaccine in Japan
1979
Initiation of large-scale human trials of Oka varicella vaccine in United States
1995
Licensing of Oka varicella vaccine in United States for healthy children aged
12 months and older and in VZV-seronegative adults
1995
First use of Oka varicella vaccine as live-recombinant vaccine (R-Oka) for protection
against other human viruses in animal clinical trials
1996
First human clinical trial of heat-inactivated Oka vaccine in United States for
VZV-seropositive adults aged 55 years and older, to decrease incidence and
severity of zoster
1998
Initiation of ‘‘Shingles Prevention Study,’’ a large-scale clinical trial in United States of
live-attenuated Oka vaccine for VZV-seropositive adults aged 55 years and older to
decrease the incidence and severity of zoster
2002
Completion of the DNA genome sequences of the Oka vaccine and its parental virus,
for mapping of potential attenuation mutations
efFcacy in inducing neutralizing antibody
to VZV and protection from varicella
disease and complications. Approximately
90% of VZV-seronegative healthy children
and adults who received a single dose
of Oka varicella vaccine in prelicensure
clinical
trials
were
protected
from
illness when naturally exposed to VZV,
and essentially all of those vaccinated
individuals who did have ‘‘breakthrough’’
varicella after natural exposure to VZV
were
protected
from
severe
disease.
Several
studies
of
varicella
outbreaks
in preschool and day-care centers since
the
Varivax
(Merck
&
Co.)
vaccine
was
licensed
in
the
spring
of
1995
suggest
that
the
level
of
protection
against varicella in some populations may
be much lower than 90%, especially
if
the
children
were
immunized
at
12 months rather than at 15 to18 months
of age, but the disease in vaccinated
children was milder than in unvaccinated
children in the same outbreak. Detailed
clinical studies indicate that there is
an
inverse
relationship
between
the
titers
of
anti-VZV
antibody
at
six
weeks postvaccination and the long-term
incidence of ‘‘breakthrough’’ varicella, so
that speciFc immunity induced by the
vaccine does correlate with protection. The
Oka varicella vaccine has not been licensed
for immunocompromised children who
are most at risk for dangerous disease,
although these children could beneFt
most from the varicella vaccine. The live-
attenuated varicella vaccine is somewhat
less effective in this population and may
actually cause a mild form of varicella.
A second generation of the Oka/Merck
varicella vaccine, known as Varivax II, has
the same safety and efFcacy characteris-
tics of Varivax, but has the advantage of
being refrigerator-stable. A similar vac-
cine has been developed by SmithKline
Beecham Biologicals and is known as
VARILRIX. There are incentives to de-
velop safer alternatives to these current
live-attenuated vaccines because of the
ability of the Oka vaccine virus to es-
tablish latent infection and subsequently
reactivate, and because of the unknown
duration of immunity from a single child-
hood immunization compared to infection
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