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J Infect Dis. 2016 Nov 1;214(9):1341-1348. Epub 2016 Aug 11.

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.

Author information

1
CMV Research Foundation.
2
Department of Pediatrics.
3
Department of Internal Medicine, Virginia Commonwealth University, Richmond.
4
University of Pennsylvania.
5
Wistar Institute, Philadelphia, Pennsylvania.
6
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, Georgia.
7
International AIDS Vaccine Initiative, New York.
8
Department of Molecular Microbiology and Immunology, Oregon Health and Science University.
9
Department of Biology, University of Portland, Oregon.
10
3-V Biosciences, Menlo Park, California.

Abstract

BACKGROUND:

 Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.

METHODS:

 The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted.

RESULTS:

 There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+ T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+ T-cell responses to IE1; 3 responded to 1-2 additional antigens.

CONCLUSIONS:

 The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate.

CLINICAL TRIALS REGISTRATION:

NCT01195571.

KEYWORDS:

cytomegalovirus; pregnancy; transplantation; vaccines

Comment in

PMID:
27521362
PMCID:
PMC5079366
DOI:
10.1093/infdis/jiw365
[Indexed for MEDLINE]
Free PMC Article

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