Development of novel vaccine strategies against human cytomegalovirus infection based on subviral particles

Pepperl-Klindworth, Sandra; Frankenberg, Nadine; Plachter, Bodo

doi:10.1016/s1386-6532(02)00099-9

Cited by 21 publications

(18 citation statements)

References 38 publications

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“…3A). As expected (46), DB lysates revealed a complex composition of Ͼ10 protein bands vis- ible by silver staining (Fig. 3A) or Coomassie blue staining (not shown), reflective of the inclusion of multiple tegument proteins and glycoproteins (44).…”

Section: Production Of Dbs Composed Of Multiple Glycoproteins and Tegsupporting

confidence: 76%

“…In the virion fraction, 75 to 80% of the particles included capsids, and the average particle size was 180 nm by NTA and 180 to 215 nm by TEM. In previous studies of DB antigenicity, in-gel comparisons of DB lysates and BSA standards have been standard (45,46,54). Here, we first determined protein quantity by BCA and then compared DBs with BSA by gel analysis (Fig.…”

Section: Production Of Dbs Composed Of Multiple Glycoproteins and Tegmentioning

confidence: 99%

“…In addition, a DB vaccine would not require delivery of viral DNA or rely on replication, and both qualities would improve safety. Previous evaluations in mice have established that DBs purified by conventional methods induce neutralizing antibodies, preventing infection of fibroblasts in vitro, induce T cell responses specific for pp65, and are immunogenic without addition of adjuvant (45,46). However, the specificity of the humoral immune response and the breadth of the cellular immune response to DBs have not been established.…”

mentioning

confidence: 99%

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Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells

Cayatte

Schneider-Ohrum

Wang

et al. 2013

J Virol

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Section: Production Of Dbs Composed Of Multiple Glycoproteins and Tegsupporting

confidence: 76%

Section: Production Of Dbs Composed Of Multiple Glycoproteins and Tegmentioning

confidence: 99%

mentioning

confidence: 99%

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Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells

Cayatte

Schneider-Ohrum

Wang

et al. 2013

J Virol

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“…The reason for this lack of transport of pp65 in DC is unknown, but was also seen in other pAPC exposed to DB. 9 These experiments showed that DC, being an important pAPC, were loaded exogenously with pp65 by DB. To prove that this loading was immunologically relevant, ie that cells were sensitized to become CTL targets after loading, ELISPOT-and chromium release analyses were performed.…”

mentioning

confidence: 94%

Protein delivery by subviral particles of human cytomegalovirus

Pepperl-Klindworth¹,

Frankenberg²,

Riegler

et al. 2003

Gene Ther

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Direct protein delivery is an emerging technology in vaccine development and gene therapy. We could previously show that subviral dense bodies (DB) of human cytomegalovirus (HCMV), a beta-herpesvirus, transport viral proteins into target cells by membrane fusion. Thus these non-infectious particles provide a candidate delivery system for the prophylactic and therapeutic application of proteins. Here we provide proof of principle that DB can be modified genetically. A 55 kDa fusion protein consisting of the green fluorescent protein and the neomycin phosphotransferase could be packed in and delivered into cells by recombinant DB in a functional fashion. Furthermore, transfer of protein into fibroblasts and dendritic cells by DB was efficient, leading to exogenous loading of the MHC-class I antigen presentation pathway. Thus, DB may be a promising basis for the development of novel vaccine strategies and therapeutics based on recombinant polypeptides.

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“…We have focused on the development of a vaccine based on subviral dense bodies (DB) [21,22]. DB enter cells in a way comparable to virions and thereby deliver their proteinaceous content into the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Refinement of strategies for the development of a human cytomegalovirus dense body vaccine

Mersseman

Böhm

Holtappels

et al. 2008

Med Microbiol Immunol

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Development of a vaccine against human cytomegalovirus (HCMV) infection has been identiWed as a high priority goal in biomedical research, yet no vaccine has been licensed until now. Recombinant subviral dense bodies (recDB) are a promising basis for the establishment of such a vaccine. In this article, strategies for the generation of recDB, based on recombination-mediated genetic engineering of the 230 kb HCMV DNA genome in E. coli are outlined. Analysis of viral mutants that were constructed in this process provided the proof-of-principle that heterologous antigens can be packaged into recDB and that these particles prime CD8 T cell responses against the recombinant antigen upon their application to HLA-A2 transgenic mice.

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Development of novel vaccine strategies against human cytomegalovirus infection based on subviral particles

Cited by 21 publications

References 38 publications

Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells

Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells

Protein delivery by subviral particles of human cytomegalovirus

Refinement of strategies for the development of a human cytomegalovirus dense body vaccine

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