In 1992, Drs. Martha Yow and Gail Demmler published an editorial entitled,“Congenital Cytomegalovirus Disease-20 Years Is Long Enough” 1. This editorial pointed out that, in spite of the long-standing recognition of the major public health importance of congenital cytomegalovirus (CMV) infection, that few solutions had been forthcoming. In no area has the lack of progress been more frustrating than in the realm of CMV vaccine development. Although a number of vaccine strategies have been considered and developed, few have advanced in the clinic to the stage of efficacy testing. One vaccine candidate that reached the stage of efficacy testing was a live, attenuated CMV vaccine, the Towne vaccine. As reviewed by Dr. Stanley Plotkin2, three randomized, controlled, double blind studies in renal transplant patients demonstrated that vaccination with Towne did not prevent these patients from being infected with CMV, but that vaccination did considerably modify the severity of disease in this setting. In contrast, the results of a study in adult women with young children attending day-care centers, who were given either Towne vaccine or placebo, were disappointing. The infection rate did not differ between vaccinated and control mothers, although the resistance of naturally infected women to CMV infection was striking. The conclusion was that, although the Towne strain vaccine was immunogenic, the immunity engendered does not appear to be as robust as that which occurs after natural infection, possibly due to the titer of neutralizing antibodies, which was lower after Towne vaccination than after natural infections.

With these results in perspective, preclinical development of many new CMV vaccine approaches in the past 15 years has focused on strategies designed to either optimize the neutralizing antibody response, or to improve the immunogenicity of live, attenuated vaccines3. The CMV envelope glycoprotein B (gB) has been focus of vaccine approaches aimed at inducing neutralizing antibody responses. A variety of expression technologies have been developed to express gB [Table 1], and these vaccines are undergoing evaluation in several clinical studies. Results in animal models have been encouraging with respect of the ability of a gB vaccine to prevent congenital CMV infection and disease4. Disappointingly, however, to date no clinical trial of any CMV vaccine has been shown to have an impact on acquisition of CMV infection. To the great excitement of the CMV vaccine community, this situation has now changed. The recent Congenital Cytomegalovirus Workshop at the Centers for Disease Control in Atlanta, Georgia (www. cmvconference2008. com), organized under the outstanding leadership of Drs. Michael Cannon (CDC) and Lenore Pereira (University of California, San Francisco),