Source:http://linkedlifedata.com/resource/pubmed/id/11727514
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2001-11-30
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pubmed:abstractText |
Cytomegalovirus-caused diseases are preventable. We believe that both neutralising antibodies and cell-mediated immunity are necessary for prevention. Of the CMV proteins, gB and pp65 are the minimum requirements in a vaccine to induced neutralising antibodies and cytotoxic T-lymphocyte (CTL) responses. Immunisation with additional proteins, e.g., gH, gN for neutralising antibodies and IE1exon 4 and pp150 for CTL responses, would strengthen protective immune responses. Approaches to development of a safe and effective cytomegalovirus (CMV) vaccine for the prevention of CMV diseases include: a) a live attenuated vaccine (Towne strain); b) recombinant constructs of the attenuated Towne and the virulent Toledo CMV strains; c) subunit glycoprotein B (gB) adjuvanted with MF59 to induce neutralising antibodies; d) phosphoprotein 65 (pp65) peptide-based vaccines to induce (CTL) for use in therapeutic vaccination; e) canarypox-CMV recombinants, e.g., ALVAC-CMV(gB) and ALVAC-CMV (pp65) to induce neutralising antibodies and CTL responses, respectively; f) DNA plasmids containing the genes for gB and pp65; g) dense bodies containing the key antigens. The attenuated Towne strain, gB/MF59, ALVAC-CMV(gB) and ALVAC-CMV(pp65) approaches have already been tested in clinical trials. The Towne vaccine induced neutralising antibodies and cell-mediated immunity (including CTLs) mitigated CMV disease in seronegative renal transplant recipients and protected against a low-dose virulent CMV challenge in normal volunteers but did not prevent infection in mothers of children excreting CMV. Immunisation with gB/MF59 resulted in high levels of neutralising antibodies in seronegative subjects. ALVAC-CMV(gB) did not induce neutralising antibodies but primed the immune system to a Towne strain challenge, while ALVAC-CMV(pp65) induced long-lasting CTL responses in all originally seronegative volunteers, with CTL precursor frequency similar to naturally seropositive individuals. These results suggest that CMV diseases can be prevented or attenuated and that a vaccine combining ALVAC-CMV(pp65) with gB/MF59 may induce sufficient CTLs and neutralising antibodies to protect against CMV diseases. Meanwhile, other approaches such as DNA peptide and dense body vaccines, should enter Phase I trials. All candidate vaccines will have to demonstrate that immunogenicity provides protection. Combined vaccines containing canarypox (ALVAC) vectors to express CMV-pp65 to induce CTLs and of subunit gB, given together with an appropriate adjuvant to induce neutralising antibodies, should be tested in a target population for the prevention of CMV infection and disease.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1471-2598
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
401-12
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading | |
pubmed:year |
2001
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pubmed:articleTitle |
Development of a cytomegalovirus vaccine: lessons from recent clinical trials.
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pubmed:affiliation |
Wistar Institute/Albert Szent-Gyorgyi Medical University, Aventis Pasteur, Swiftwater, PA, USA.
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pubmed:publicationType |
Journal Article,
Review
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