A phase 1 study of 4 live, recombinant human cytomegalovirus Towne/Toledo chimeric vaccines.
BACKGROUND
Human cytomegalovirus (HCMV) infection acquired in utero often results in severe consequences, including mental retardation and deafness. Although not evaluated for this indication, live attenuated HCMV vaccines based on the Towne strain are well-tolerated and have demonstrated moderate efficacy in other clinical settings.


METHODS
To produce live HCMV vaccine candidates that retain the excellent safety profile of the Towne strain but are more immunogenic, the genomes of the Towne strain and the unattenuated HCMV Toledo strain were recombined to yield 4 independent chimeric vaccine candidates. These vaccine candidates were evaluated in 20 HCMV-seropositive persons, in a phase 1, double-blinded, placebo-controlled trial. Participants received a single dose of vaccine or placebo, and the safety and tolerability of the vaccine candidates were evaluated.


RESULTS
There was no difference in systemic symptoms between the vaccine and placebo recipients. As a group, vaccine recipients experienced more injection-site reactions than did placebo recipients; however, these were generally minor and short-lived. Vaccine virus could not be detected in blood, urine, or saliva samples obtained from any vaccine recipient.


CONCLUSIONS
The Towne/Toledo chimeric vaccine candidates were well tolerated and did not cause systemic infection. Additional human trials are warranted to further evaluate the potential of these vaccine candidates as live virus vaccines.
Heineman
Thomas C
TC
Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri 63110, and Division of Pediatric Infectious Diseases, Children's Hospital Medical Center, University of Cincinnati, OH, USA. heinemtc@slu.edu
Schleiss
Mark
M
Bernstein
David I
DI
Spaete
Richard R
RR
Yan
Lihan
L
Duke
Greg
G
Prichard
Mark
M
Wang
Zhaoti
Z
Yan
Qing
Q
Sharp
Margaret A
MA
Klein
Nicola
N
Arvin
Ann M
AM
Kemble
George
G
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008923:Missouri; D009820:Ohio; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000276:immunology
D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated