A Phase I Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimeric Vaccines
Year of Publication
Heineman, TC; Schleiss, M; Bernstein, DI; Spaete, RR; Yan, L; Duke, G; Prichard, M; Wanh, Z; Yan, Q; Sharp, MA; Klein, N; Arvin, AM; Kemble, G
J Infec Dis
Antibodies- Viral; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; DNA- Viral; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Male; Middle Aged; Missouri; Ohio; Polymerase Chain Reaction; Recombinant Fusion Proteins
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.