Cytomegalovirus and Varicella–zoster Virus Vaccines
157
sometimes life-threatening disease involv-
ing the lungs, liver, or eyes and requires
antiviral therapy. The drug of choice is gan-
ciclovir, a compound that inhibits CMV
replication by speciFcally inhibiting the vi-
ral DNA polymerase, but can often display
signiFcant toxicity.
1.2
Naturally Acquired Protective Immunity
The acquired immunity to CMV follow-
ing primary infection is typically sufFcient
to prevent disease in immunocompetent
individuals. However, asymptomatic re-
infection with different antigenic strains
of CMV or reactivation of latent CMV
can occur in healthy, CMV-seropositive
adults. The antibody and cytotoxic T-cell
responses induced by prior CMV infec-
tion of females appear insufFcient to
prevent virus reactivation during preg-
nancy and congenital infection, but the
resulting congenital infections are almost
always asymptomatic. Transplacental anti-
body can also protect newborns and infants
from infection or disease after birth until
this maternal antibody disappears from
circulation.
Immunocompetent children and adults
acquire life-long immunity to varicella/chi-
ckenpox following this initial infection
with VZV, even though the viral genetic
information persists in a latent form in
nerve tissue known as sensory ganglia.
SpeciFc antibody capable of neutralizing
virions can be highly protective and can
prevent initial infection with VZV, as
demonstrated by the protective effects of
maternally acquired antibody in prevent-
ing varicella/chickenpox in most infants
less than 12 months of age. This antibody
is transported across the placenta from
mother to fetus late in pregnancy and is
a natural form of passive immunization
against a large number of infectious organ-
isms. SpeciFc cytotoxic T-cell responses
are necessary in addition to neutralizing
antibody in controlling infection and lim-
iting disease once the virus infection has
occurred. These acquired cytotoxic T-cell
responses to VZV proteins are essential
in preventing or delaying reactivation of
latent virus, consistent with the highest
incidence of zoster/shingles in the elderly
with a natural decrease in the activity of
the immune system.
1.3
EfFcacy of Live-attenuated Varicella Vaccine
in Preventing Chickenpox
The most commonly used varicella vac-
cine is a live-attenuated VZV strain that
was developed in the 1970s from a hu-
man clinical isolate of virus from a patient
with typical varicella (Table 1). Long-term
propagation and multiple passaging of this
Oka strain in human diploid Fbroblast cell
culture led to virus that replicated bet-
ter in cell culture but was attenuated for
replication and pathogenicity in humans,
thereby causing infection without disease
in most healthy persons when adminis-
tered by intramuscular or subcutaneous
infection. The licensed Oka vaccine strain
of VZV can be distinguished from corre-
sponding clinical isolates of VZV on the
basis of restriction endonuclease analysis
of the viral DNA genome. In addition,
determination of the complete DNA se-
quences of the Oka vaccine virus and
its parental virus has recently been com-
pleted to allow detailed comparisons and
identiFcation of speciFc gene alterations
responsible for the
in vivo
attenuation of
the vaccine strain.
Extensive studies of the varicella vaccine
in large numbers of healthy children have
demonstrated a high degree of safety and
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