Biology Reference
In-Depth Information
Table 3
Potential novel HCMV vaccine strategies that have been explored in preclinical/animal
model studies
gM/gN (gcII complex)
Major glycoprotein constituent of virion
Majority of human sera contain anti-gcII antibodies
gM/gN DNA vaccine immunogenic in mice
gH/gL/gO (gcIII complex)
Target of neutralizing antibody response in setting
of HCMV infection
gH Vaccine based on MCMV homolog protective in murine model
when expressed using recombinant adenovirus technique
Essential/nonstructural
DNA polymerase (UL54) and helicase (UL105)
gene products as novel
as novel T cell targets
CTL targets
Protective in MCMV model when expressed as DNA vaccines
Prime-boost strategy
Prime with cocktail of plasmid DNA vaccines
Boost with formalin-inactivated viral particles
Induces sterilizing immunity in MCMV model
Bacterial artificial
Protective in MCMV model following delivery
chromosome (BAC)
in bacteria with reconstitution of virus in vivo
vaccines
Protective in GPCMV model when administered
as replication-disabled DNA vaccine
Offers theoretical potential for specifically engineered vaccines
with deletions in putative pathogenesis or immune evasion
genes: improved immunogenicity
Peptide vaccines
Effective in MCMV model following mucosal immunization
with cholera toxin
Allows simultaneous immunization against broad range
of CTL epitopes: polyepitope vaccine
Requires knowledge of HLA status of vaccine recipient; best
suited to HCMV vaccination in transplantation setting?
complexes in virions from clinical isolates: gH/gL and gO is one; the other is gH/gL,
pUL128, pUL130 (Wang and Shenk 2005; Adler et al. 2006). Antibodies to
pUL128, pUL130, or pUL131 can neutralize infection of epithelial cells but have no
effect on infection of fibroblasts. Whether these observations will be translated into
an expanded list of candidate subunit targets remains to be determined. Since acqui-
sition of new antibody specificities to gH in the setting of reinfection with a new
strain of HCMV is associated with symptomatic congenital transmission in pregnant
patients (Boppana et al. 2001) and with adverse outcomes following renal transplan-
tation (Ishibashi et al. 2007), these observations might be important for potential
gcIII-based vaccine design. Proof-of-concept has been studied with vaccines based
on the MCMV gH homolog using recombinant vaccinia (Rapp et al. 1993) and ade-
novirus (Shanley and Wu 2005) vectors; of these two approaches, the adenovirus-
expressed gH vaccine was more effective as a vaccine against MCMV.
Regulatory/Structural HCMV Proteins Involved in T Cell Response
Most attention on HCMV vaccine candidates that elicit potentially protective T cell
responses has been focused on the pp65 and IE1 gene products. However, recent
evaluation of the T cell responses in HCMV-seropositive individuals identified a
