Vaccination against cytomegalovirus
Like varicella zoster virus (VZV), human cytomegalovirus (HCMV) causes disease after both primary and recurrent infections. The former is more serious, particularly in pregnant women, who may transmit the virus to their offspring, with a high risk of ment
- PDF / 2,018,726 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 8 Downloads / 167 Views
Summary. Like varicella zoster virus (VZV), human cytomegalovirus (HCMV) causes disease after both primary and recurrent infections. The former is more serious, particularly in pregnant women, who may transmit the virus to their offspring, with a high risk of mental retardation and deafness. Various experimental vaccines are in development, ranging from live, attenuated HCMV, subunit envelope glycoprotein, poxvirus vectors with CMV genes inserted, and plasmid DANN. Active immunization. Attenuated live vaccines The first attempts to immunize against human cytomegalovirus (CMV) were pursued in the 1970s by two groups, one at St. George's Hospital in London led by Stephen Elek [15, 36], and the other my own group at Children's Hospital and the Wistar Institute of Philadelphia [45]. The British group started with the prototype laboratory-adapted AD-169 strain, whereas we started with a new isolate from a congenitally infected infant named Towne. Both vaccines were based on classic live-attenuated viruses which induced seroconversion in vaccinees by subcutaneous injection, with slight and tolerable local and systemic symptoms. The development of the Towne strain as a vaccine started in the mid-1970s, based on the simple idea that passage of the virus in cell cultures would eventually succeed in attenuating it for humans. The only practical cell substrate was human fibroblast cell strains, but in fact this was also the logical substrate, in that our laboratory had used it to grow attenuated rubella, attenuated polio, and inactivated rabies viruses [43]. Differences in in vitro markers between high-passage and low-passage Towne virus were identified [70], but because human CMV will not infect other species, precluding the use of any heterologous animal models, only clinical trials could tell us whether the virus had been attenuated. Accordingly, the first clinical trial of the Towne virus (125 th passage in MRC-5 cells) was performed in healthy male young adult volunteers [44]. The
A. A. Gershon et al. (eds.), Immunity to and Prevention of Herpes Zoster © Springer-Verlag Wien 2001
S. A. Plotkin
122
Table 1. Properties of Towne strain live attenuated cytomegalovirus vaccine •
Safety - No systemic symptoms or clinical laboratory abnormalities - Not isolated from those recently vaccinated - No evidence for latency after immunosuppression - Injection site reaction common without systemic side effects - No depression of cell-mediated immunity or alteration of CD4/CD8 ratio
•
Immunogenicity - Regularly elicits humoral response, including neutralizing antibody - Induces lasting lymphocyte proliferative responses - Induces HLA-restricted cytotoxicity
•
Efficacy - In seronegative renal allograft recipients, does not prevent infection but does decrease frequency and mitigate severity of CMV-induced disease - In normal volunteers, protects against low-dose wild-type challenge - In mothers of children excreting CMV, did not prevent infection
observations, later confirmed in many volunteers of both sexes [32], were that the
Data Loading...
