Although cytomegalovirus (CMV) produces an uncommon mononucleosis-like syndrome in immunocompetent patients, its potential effects in the newborn and immunocompromised patient can be devastating. Congenital CMV is the most com- mon intrauterine infection in the United States, and an esti- mated 8000 American infants develop neurologic or fatal complications each year because of this disease (281). This infection represents a common problem for HIV-infected per- sons, typically leading to neurologic syndromes or retinitis. CMV is also the most signiﬁcant infectious agent in organ transplant recipients, and is often a factor in graft rejection. Hematopoietic stem cell transplant recipients are immuno- compromised for a period of time and may develop progressive CMV infection (282). Over two-thirds of transplant recipients develop CMV infection or reactivation within 4 months of transplantation (212). CMV is further described in Chapter 3.
Several types of CMV vaccines are currently under eval- uation. The ﬁrst of these is the live attenuated Towne strain vaccine, which was ﬁrst developed in the mid-1970s. Clinical studies in seronegative renal allograft recipients showed that the vaccine did not prevent infection, but signiﬁcantly reduced the incidence of severe disease by approximately 85% (283,284). Another study evaluated the effect of CMV vaccine in prevent- ing child-to-mother transmission of CMV acquired in daycare centers (285). The infection rate for vaccinated mothers was no different than placebo, while naturally seropositive moth- ers were protected. These disappointing results showed that the Towne strain vaccine did not induce immunity as effec- tively as natural infection. Concerns continue to focus on the use of a live virus that constitutes a major risk in a transplant patient. Current work is underway to develop improved ver- sions of the Towne strain vaccine (286,287).
Subunit glycoprotein B (gB) vaccines that circumvent the use of viral vectors have also been evaluated for CMV immu- nization. This approach may use full-length proteins that are incorporated into a cell as endogenous proteins. CMV gB can be combined with an adjuvant called MF59 and, in one trial, stimulated the neutralizing antibody for at least 12 months (288). Clinical studies of the vaccine in healthy toddlers and adults have shown good immune response, but neutralizing antibodies rapidly declined in the 6 months following the third dose (289,290). A fourth dose in adults led to higher antibody levels, though titers declined again in 6 months (290). Further long-term data on this study is not yet available. A clinical vaccine efﬁcacy study in mothers is currently underway to evaluate the effects on the antibody response (291). The canarypox-gB recombinant vaccine has been developed and evaluated as a candidate CMV vaccine. Initial trials have demonstrated a weak antibody response after multiple doses, but additional studies are currently evaluating its potential as a primer for boosting of subsequent Towne strain injections (292). Normal CD8+ cytotoxic T lymphocyte response to CMV involves a few proteins that could be candidates for vaccines (282). Polysaccharide nanoparticles may be useful in stimulat- ing CMV-speciﬁc TH cells and CMV-speciﬁc CD8+ cytotoxic T lymphocytes. This system is promising in that it is nonviral. It remains to be tested in humans to determine efﬁcacy (282). Other potentially hopeful avenues for CMV vaccines include DNA plasmids (293), an HLA-restricted peptide-based vaccine (294), and lipopeptides.