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 microg 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.


CONCLUSIONS
The CMV gB vaccine is well-tolerated and highly immunogenic in toddlers.
Mitchell
Douglas K
DK
Center for Pediatric Research, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, VA, USA.
Holmes
Sandra J
SJ
Burke
Rae Lynn
RL
Duliege
Anne Marie
AM
Adler
Stuart P
SP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis*; D000917:Antibody Formation; D002675:Child, Preschool; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D013185:Squalene