Cytomegalovirus Vaccine

5 Jun

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.

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