August 1997
WASHINGTON, D.C. — Results of a Phase 1 trial of a cytomegalovirus (CMV) vaccine in toddlers indicate the vaccine is well tolerated and highly immunogenic, according to researchers at the Eastern Virginia Medical School.
CMV is a significant cause of congenital viral infection; about one in every 100 children born in the United States has a congenital CMV infection, said lead investigator Douglas K. Mitchell, MD, assistant professor of pediatrics at EVMS.
Up to 10% of infected infants have major manifestations at birth. But signs of congenital infection, including intrauterine growth retardation, hepatosplenomegaly, jaundice, thrombocytopenia, hemolytic anemia, microcephaly, intracranial calcification, chorioretinitis and sensorineural deafness, occur uncommonly in these infected newborns.
"If an adult gets CMV — or an older child — it's really not a big deal. But, if a woman gets CMV for the first time during pregnancy, there's a 40% chance of the baby becoming infected, which could have severe effects," he said. "CMV can be a devastating congenital illness."
The trial was conducted in 18 CMV-seronegative children 12-35 months of age. The Chiron CMV gB vaccine is safe and immunogenic in toddlers. The antibody responses noted in these toddlers were significantly higher than the 149 adults who received three doses of the same vaccine in other trials.
Each child received, at 0, 1 month and 6 months of age, either 20 mg of CMV gB/MF59 vaccine or a control hepatitis A vaccine.
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CMV gB/MF59 vaccine is a purified recombinant gB protein produced in a Chinese hamster ovary cell culture, combined with MF59, a new proprietary oil-in-water emulsion that is used as the adjuvant. All other approved vaccines use alum as the adjuvant, which enhances the immune response to the immunogen. Chiron's original studies with CMV gB vaccine showed a better immune response with the MF59 adjuvant than with alum adjuvant.
"Antibodies to the gB antigen are thought to represent 60% to 70% of the CMV-specific neutralizing antibody response. So, it is expected that this vaccine would provide protection," Mitchell said. "Still, more studies are needed."
The study was open-labeled for the first six children and then double-blinded and randomized. Children were monitored for local and systemic reactions for seven days after each shot. Serologic tests for antibody were obtained pre-immunization, one month after dose one, one month after dose two in 50% of subjects, and one month after dose three in all subjects.
Reactogenicity was low; five post-immunization reactions were seen in four patients. The geometric mean titers (GMTs) of antibody to gB rose significantly: from zero at pre-immunization to an average of 27,457 after dose two and an average of 98,264 after dose three. Neutralizing antibody reciprocal GMTs also rose from zero at pre-immunization to an average of 90 after dose two and an average of 638 after dose three. After the third dose, all children had titers higher than those observed in naturally infected adults.
For more information:
- Mitchell DK, Homes SJ, Burke RL, et al. Immunogenicity of a recombinant cytomegalovirus (CMV) gB vaccine in toddlers. Abstract 745. Presented at the Annual Pediatric Academic Societies' Meeting, Washington, D.C. May 2-6, 1997.
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