Clinical Trials of Immunization with the Towne 125 Strain of Human Cytomegalovirus

Plotkin, Stanley А.; Farquhar, John D.; Hornberger, Elizabeth

doi:10.1093/infdis/134.5.470

Cited by 173 publications

(63 citation statements)

References 15 publications

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“…In fact, Penfold et al (33) have recently shown that one of the genes deleted in laboratory strains encodes for a chemokine. Clinical trials based on immunization of healthy volunteers with AD169, Towne, or Toledo strains indicate that the low passaged Toledo strain exhibits a significantly higher virulence, being able to cause clinically apparent disease (34), compared with other two highly passaged strains (35)(36)(37)(38). It is thus possible that gene products involved in the immunoescape and survival of the virus in the host are deleted in the laboratory strains (33).…”

Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus Strain-Dependent Changes in NK Cell Recognition of Infected Fibroblasts

Cerboni

Mousavi‐Jazi

Linde

et al. 2000

The Journal of Immunology

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NK cells play a key role in the control of CMV infection in mice, but the mechanism by which NK cells can recognize and kill CMV-infected cells is unclear. In this study, the modulation of NK cell susceptibility of human CMV (hCMV)-infected cells was examined. We used a human lung and a human foreskin fibroblast cell line infected with clinical isolates (4636, 13B, or 109B) or with laboratory strains (AD169, Towne). The results indicate that all three hCMV clinical isolates confer a strong NK resistance, whereas only marginal or variable effects in the NK recognition were found when the laboratory strains were used. The same results were obtained regardless of the conditions of infection, effector cell activation status, cell culture conditions, and/or donor-target cell combinations. The NK cell inhibition did not correlate with HLA class I expression levels on the surface of the target cell and was independent of the leukocyte Ig-like receptor-1, as evaluated in Ab blocking experiments. No relevant changes were detected in the adhesion molecules ICAM-I and LFA-3 expressed on the cell surface of cells infected with hCMV clinical and laboratory strains. We conclude that hCMV possesses other mechanisms, related neither to target cell expression of HLA-I or adhesion molecules nor to NK cell expression of leukocyte Ig-like receptor-1, that confer resistance to NK cell recognition. Such mechanisms may be lost during in vitro passage of the virus. These results emphasize the differences between clinical hCMV isolates compared with laboratory strains.

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Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus Strain-Dependent Changes in NK Cell Recognition of Infected Fibroblasts

Cerboni

Mousavi‐Jazi

Linde

et al. 2000

The Journal of Immunology

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“…The AD169 and Towne HCMV strains were developed as vaccine candidates by serial passages in HELFs with the intention of attenuating their virulence [43,44], thus reducing or suppressing their ability to replicate in ECs [45,46]. This line of thought was confirmed by the sequential propagation of four recent HCMV isolates in HELFs [37].…”

Section: Hcmv Leukocyte and Endothelial Cell Tropismmentioning

confidence: 99%

“…In the first group, Towne and AD169 viruses both carry a~15 kb deletion in the ULb¢ region [52], as well as various mutations in UL128L, as a result of multiple passaging in HELFs [43,44]. Thus, both Towne and AD169 have lost the ability to infect endothelial and epithelial cells and lack a functional PC.…”

Section: Development Of An Hcmv Vaccine: Potential Role Of the Pcmentioning

confidence: 99%

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

Gerna

Revello

Baldanti

et al. 2017

Journal of General Virology

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Between the 1980s and 1990s, three assays were developed for diagnosis of human cytomegalovirus (HCMV) infections: leuko (L)-antigenemia, L-viremia and L-DNAemia, detecting viral protein pp65, infectious virus and viral DNA, respectively, in circulating leukocytes Repeated initial attempts to reproduce the three assays in vitro using laboratory-adapted strains and infected cell cultures were consistently unsuccessful. Results were totally reversed when wild-type HCMV strains were used to infect either fibroblasts or endothelial cells. Careful analysis and sequencing of plaque-purified viruses from recent clinical isolates drew attention to the ULb¢ region of the HCMV genome. Using bacterial artificial chromosome technology, it was shown by both gain-of-function and loss-of-function experiments that UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. In addition, a number of clinical isolates passaged in human fibroblasts had lost both properties (leuko-tropism and endothelial cell-tropism) when displaying a mutation in the UL131-128 locus

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“…Another important aspect of CMV is infection of patients undergoing renal transplantation (for review, see Osborn, 1981). In an attempt to prevent infection by exogenous CMV, two groups of virologists initiated vaccination with live, cell culture-passaged CMV (Elek & Stern, 1974;Plotkin et al, 1976). However, since human CMV is highly speciesspecific, these vaccines have no experimental animal model in which pathogenicity and the mechanism of immunity can be studied.…”

Section: Introductionmentioning

confidence: 99%

Pathogenicity and Immunogenicity of Temperature-sensitive Mutants of Murine Cytomegalovirus

Tonari

Minamishima

1983

Journal of General Virology

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SUMMARYTwo temperature-sensitive (ts) mutants (ts 21 and ts 24), which could complement each other, were isolated from cell culture-passaged murine cytomegalovirus (CC-MCMV). Characterization in vivo revealed that ts 21 lacked pathogenicity for suckling mice, neurovirulence for weanling mice and productive chronic infection in the salivary gland, whereas ts 24 was positive only for the first two parameters; both mutants retained immunogenicity comparable to that of the wild-type CC-MCMV. The immunogenicity of ts 21 and ts 24 was assessed by mortality of the immunized mice after challenge with virulent, salivary gland-passaged MCMV (SG-MCMV) and by replication of the challenge virus in the immunized hosts. The protective immunity conferred by ts 21 was maintained over a period of 3 months without production of infectious viruses in the salivary gland.

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Clinical Trials of Immunization with the Towne 125 Strain of Human Cytomegalovirus

Cited by 173 publications

References 15 publications

Human Cytomegalovirus Strain-Dependent Changes in NK Cell Recognition of Infected Fibroblasts

Human Cytomegalovirus Strain-Dependent Changes in NK Cell Recognition of Infected Fibroblasts

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

Pathogenicity and Immunogenicity of Temperature-sensitive Mutants of Murine Cytomegalovirus

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