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Clinical Trial
. 2016 Nov 1;214(9):1341-1348.
doi: 10.1093/infdis/jiw365. Epub 2016 Aug 11.

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

Stuart P Adler  1 , Anne-Marie Manganello  1 , Ronzo Lee  2 , Michael A McVoy  2 , Daniel E Nixon  3 , Stanley Plotkin  4   5 , Edward Mocarski  6 , Josephine H Cox  7 , Patricia E Fast  7 , Pavlo A Nesterenko  8 , Susan E Murray  8   9 , Ann B Hill  8 , George Kemble  10
Affiliations
Clinical Trial

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

Stuart P Adler et al. J Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Neutralizing responses measured using ARPE-19 epithelial cells (A) or MRC-5 fibroblasts (B) for subjects 34, 35, and 36, who received 1000 plaque-forming units of chimera 4 vaccine.
Figure 2.
Figure 2.
Geometric mean titers (GMTs) indicating neutralizing responses 12 weeks after immunization (horizontal line), with minima and maxima (solid vertical lines), among subjects who received 100 or 1000 plaque-forming units of chimera 2 or 4 vaccine. The GMTs in naturally seropositive subjects, determined using a fibroblast-based assay, is 25. The epithelial cell–based GMT for seropositive subjects is 3000.
Figure 3.
Figure 3.
T-cell responses to vaccination. A, Gating hierarchy for assessment of T-cell responses. Shown are IE-1 responses in 2 representative subjects. B, Proportion of seroconverters (n = 11) who mounted CD4+ or CD8+ T-cell responses to overlapping peptide pools covering the indicated proteins. C, Kinetics of CD8+ T-cell responses to IE-1 overlapping peptide pools in the indicated subjects. All subjects displayed are seroconverters, except subject 21. D, Proportion of total memory (CD95+/low) and effector memory (CD95+/lowCD28−) cells among CD8+ T cells over time for subject 23, who may have been exposed to wild-type human cytomegalovirus between week 52 and 101 after vaccination. Abbreviations: IFN-γ, interferon γ; TNF-α, tumor necrosis factor α.
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Comment in

  • 40 Years Is Long Enough!
    Demmler Harrison GJ. Demmler Harrison GJ. J Infect Dis. 2016 Nov 1;214(9):1297-1299. doi: 10.1093/infdis/jiw367. Epub 2016 Aug 11. J Infect Dis. 2016. PMID: 27521360 No abstract available.

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References

    1. Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. Outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med 1992; 326:663–7. - PubMed
    1. Stratton KR, Durch J, Lawrence RS. Vaccines for the 21st century: a tool for decision making. Washington, DC: National Academy Press, 2000. - PubMed
    1. Plotkin S. The history of vaccination against cytomegalovirus. Med Microbiol Immunol 2015; 204:247–54. - PubMed
    1. Elek SD, Stern H. Development of a vaccine against mental retardation cased by cytomegalovirus infection in utero. Lancet 1974; 1:1–15. - PubMed
    1. Plotkin SA, Furukawa T, Zygraich N, Huygelen C. Candidate cytomegalovirus strain for human vaccination. Infect Immun 1975; 12:521–7. - PMC - PubMed

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