Biology Reference
In-Depth Information
identified in up to 40% of HCMV-seropositive subjects (Slezak et al. 2007), this
gene product is also being evaluated in a number of clinical trials. These studies
to date have not involved administration of IE1 vaccine alone, but have consisted
of trivalent vaccines that also contain pp65 and gB. As noted, one expression
approach that has undergone phase 1 evaluation is that of DNA vaccination.
A trivalent DNA vaccine targeting gB, pp65, and IE1 (Vilalta et al. 2005) was
evaluated in a phase 1 trial involving a total of 40 healthy adult subjects (24
HCMV-seronegative, 16 HCMV-seropositive). Subjects received a 1-mg or 5-mg
dose of trivalent vaccine in several multidose regimens; safety and immuno-
genicity studies are ongoing (R. Moss, personal communication). IE1 has also
been expressed using the alphavirus/VRP approach. A trivalent VRP vaccine,
consisting of the IE1 gene product along with gB and pp65, is currently being
evaluated in a phase I study (Reap et al. 2007).
HCMV Vaccine Approaches in Preclinical Development
Alternative Expression Strategies for HCMV gB, pp65, and IE1
In addition to the expression strategies outlined above that have made their way
into human clinical trials, there are other modes of expression of HCMV subunit
vaccine candidates that appear useful in preclinical study. These approaches are
summarized in Table 2. One particularly promising approach is based on a
recombinant attenuated poxvirus, modified vaccinia virus Ankara. A recombinant
Ankara vaccine has been constructed that expresses a soluble, secreted form of
Table 2
Alternative subunit vaccine expression strategies proposed for HCMV gB, pp65, and IE1
Modified vaccinia virus Ankara (MVA)
High-level protein expression
Excellent immunogenicity (humoral and cellular
responses) in mice
Ability to express multiple immunogens (bivalent
or trivalent vaccines) in single construct
Preexisting immunity to poxvirus does not limit
immune response (utility for vaccinees
who have received smallpox vaccine)
Recombinant adenovirus
Potential for induction of mucosal immune responses
Replication-deficient adenoviruses available
to ensure vector safety
Efficacy in murine model using MCMV gB homolog
Transgenic plants
Recombinant HCMV gB successfully expressed
in transgenic rice
Offers potential for oral vaccination
Potential for induction of mucosal immune responses
No animal immunogenicity data yet reported
