Cytomegalovirus and Varicella–zoster Virus Vaccines
155
Virion
Complete infectious virus particle.
¥
Classical live-attenuated vaccines were developed several decades ago for two
clinically important human herpesviruses, varicella-zoster virus and human
cytomegalovirus. The varicella vaccine has been licensed for immunization of
normal children in Japan, Korea, and the United States for a number of years. In
contrast, live-attenuated cytomegalovirus has only been tested in a limited number
of studies of organ transplant recipients and healthy adult volunteers, and has not yet
been considered for licensure. A number of experimental cytomegalovirus vaccines
have been developed using molecular biology and recombinant DNA technology,
because of theoretical concerns about the long-term safety and effectiveness of the
currently available live cytomegalovirus vaccines. Some of the same techniques
are also being applied to varicella-zoster virus to develop improved vaccines that
could supplement or replace the current varicella vaccine or provide protection
against viral reactivation and zoster. The major emphasis of high-technology vaccine
development has been on the viral glycoproteins because they are the targets of
neutralizing antibody, and includes both recombinant protein subunit vaccines and
live-recombinant virus vaccines. Other virion and nonstructural viral proteins are
also being considered as immunogens for cytotoxic T-cell responses.
1
Introduction to Human Cytomegalovirus
and Varicella-zoster Virus
1.1
Human Diseases from Primary and
Recurrent Infection
Varicella-zoster virus (VZV) and human
cytomegalovirus (CMV) are both human
members of the family
Herpesviridae
,and
the vast majority of humans have been in-
fected with both CMV and VZV by the
time they reach adulthood. Along with
the six other human members, such as
herpes simplex virus (HSV) types 1 and
2 and Epstein–Barr virus, these viruses
have a common clinical feature of viral
latency and reactivation following primary
virus infection. Medical complications of
reactivation are most severe in immunode-
Fcient or immunosuppressed individuals.
VZV is the cause of the common child-
hood illness known as chickenpox or
varicella, and this disease is characterized
by a distinct vesicular rash on the trunk,
head, and limbs. VZV is a highly conta-
gious virus, easily spread by respiratory
secretions of infected individuals several
days before the appearance of skin lesions.
Complications of varicella include pneu-
monia, secondary bacterial infections, and
inflammation of the brain, known as en-
cephalitis. These complications may occur
in persons with normal immune func-
tion and may be life-threatening, but
are even more common and serious in
immunocompromised persons. Prior to
introduction of the varicella vaccine in the
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