Cytomegalovirus and Varicella–zoster Virus Vaccines
159
with ‘‘wild-type’’ virus. Two other theoret-
ical concerns with live-attenuated human
viruses are potential reversion to virulence
during replication in humans and poten-
tial oncogenicity in humans. Although the
former phenomenon clearly occurred in
another human viral vaccine, the live-oral
Sabin polio vaccine, there has been no
demonstration of similar reversion with
the Oka varicella vaccine. Even though sev-
eral other human herpesviruses are associ-
ated with speciFc human cancers, such as
B-cell lymphomas and nasopharyngeal car-
cinoma with Epstein–Barr virus and Ka-
posi’s sarcoma with human herpesvirus-8,
there is no evidence for oncogenicity as-
sociated with either natural infection by
wild-type VZV or immunization with the
live-attenuated varicella virus.
1.4
Vaccine Strategies to Prevent Congenital
CMV and Disease in Immunocompromised
Adults
The primary target for a safe and effec-
tive CMV vaccine is CMV-seronegative
females of childbearing age, to prevent
symptomatic congenital infection. An-
other target is CMV-seronegative children
or adults who are immunocompromised
and at greater risk of CMV disease. At-
tenuated and laboratory-adapted strains of
CMV were developed in the 1970s by the
same procedures as those used for the Oka
varicella vaccine. One of these, the Towne
strain, has been clinically tested in hu-
mans, but has not been shown to be effec-
tive in preventing primary infection with
VZV. The Towne strain may be too highly
attenuated, as suggested by the fact that
experimental infection does not result in
latent infection with potential reactivation.
A number of alternate vaccine strate-
gies are being developed for CMV and
also for improved and safer VZV vac-
cines, on the basis of biochemical and
immunological knowledge of the impor-
tant viral protein components of these
viruses and the viral genes encoding
these potential vaccine components. One
major and current approach for CMV vac-
cines is the production of recombinant
protein subunit vaccines in recombinant
bacteria, insect cells, or mammalian cell
culture. A second major approach is the
production of recombinant viruses that ex-
press the CMV gene and can be used as
live-recombinant vaccines, including re-
combinant vaccinia and canarypox viruses
and adenoviruses. A third approach is the
creation of less-attenuated and possibly
more-immunogenic live-attenuated CMV
vaccines by constructing genetic chimeras
between the Towne strain and a virulent
strain. ±inally, the newer technology of
plasmid DNA vaccines is being applied to
CMV and other human herpesviruses.
1.5
Vaccine Strategies to Prevent Zoster in the
Elderly and Immunocompromised Adults
Because the time interval between varicella
and zoster/shingles can be six decades or
longer and correlates with age-induced de-
creases in immune function, it may be
worthwhile to stimulate and enhance cellu-
lar immunity against VZV in seropositive
adults. This immunization of individuals
who have already been infected and still
have the virus in the latent form is clas-
siFed as ‘‘therapeutic’’ immunization, in
contrast to the typical ‘‘prophylatic’’ im-
munization of uninfected individuals with
licensed human viral vaccines. One strat-
egy is to immunize seropositive adults with
thesamedoseaschildrenorhigherdoses
of the live Oka varicella vaccine, and this
is currently being tested in a large-scale,
previous page 1479 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1481 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off