Immunogenicity of a recombinant human cytomegalovirus gB vaccine in seronegative toddlers

Background. Immunization of young children against cytomegalovirus (CMV) might decrease child-to-child and child-to-adult transmission of CMV and thereby reduce maternal infection during pregnancy. We conducted a Phase I trial in CMV-seronegative toddlers to evaluate the reactogenicity and immunogenicity of a CMV gB vaccine administered with MF59, an oil and water adjuvant. Methods. Eighteen children between 12 and 35 months of age received either 20 fig of CMV gB/MF59 (n = 15) or a control hepatitis A vaccine (n = 3) at 0, 1 and 6 months. The study was open-label for the first six children and then observer-blinded and randomized. Children were monitored for local and systemic reactions and for the development of antibodies to the envelope protein gB and CMV-neutralizing antibodies. Results. Adverse reactions were uncommon and mild. Two children were excluded from the immunogenicity analysis because they had serologic evidence of CMV infection. Reciprocal geometric mean neutralizing titers were: 0 preimmunization (n = 18); 90 (range, 53 to 188) after Dose 2 (n = 6); and 638 (range, 210 to 1645) 1 month after Dose 3 (n = 13). The reciprocal geometric mean neutralizing titers of antibody to gB by EIA were: 0 preimmunization (n = 18); 857 (range, 307 to 2073) after Dose 1 (n = 12); 27 457 (range, 9312 to 55 080) after Dose 2 (n = 6); and 98 264 (range, 35 480 to 228 780) 1 month after Dose 3 (n = 5). After Dose 3 antibody responses of toddlers were greater than those of naturally infected adults and were notably higher than among 149 adults given 3 doses of the same vaccine in other trials. Conclusion. The CMV gB vaccine is well-tolerated and highly immunogenic in toddlers.