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J Medveczky

Publications and source records attributed to J Medveczky.

5 recordsLinked to original sources
PubMed1999

Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8(+) cytotoxic T-cell epitopes.

Compelling evidence now suggests that alphabeta CD8 cytotoxic T lymphocytes (CTL) have an important role in preventing human immunodeficiency virus (HIV) infection and/or slowing progression to AIDS. Here, we describe an HIV type 1 CTL polyepitope, or polytope, vaccine comprising seven contiguous minimal HLA A2-restricted CD8 CTL epitopes conjoined in a single artificial construct. Epitope-specific CTL lines derived from HIV-infected individuals were able to recognize every epitope within the construct, and HLA A2-transgenic mice immunized with a recombinant virus vaccine coding for the HIV polytope also generated CTL specific for different epitopes. Each epitope in the polytope construct was therefore processed and presented, illustrating the feasibility of the polytope approach for HIV vaccine design. By simultaneously inducing CTL specific for different epitopes, an HIV polytope vaccine might generate activity against multiple challenge isolates and/or preempt the formation of CTL escape mutants.

AIDS Vaccines↗
PubMed1998

Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination.

Development of CD8 alphabeta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes. Here we describe a DNA plasmid encoding a polyepitope or "polytope" protein, which contained multiple contiguous minimal murine CTL epitopes. Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models. CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help. The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.

Amino Acid Sequence↗
PubMed1996

Vaccinia virus replication is independent of cellular HSP72 expression which is induced during virus infection.

HSP72 is dramatically induced in the ovaries of vaccinia virus (VV)-infected mice and associates with VV proteins. In order to investigate the role of HSP72 during vaccinia virus replication, we have constructed a recombinant vaccinia virus encoding the major inducible cellular HSP72 (VV-HSP72+) and examined the replication characteristics of this virus. VV-HSP72+ exhibited growth kinetics identical to and peak titers very similar to those of control viruses, both in vitro and in vivo. In particular, replication of VV-HSP72+ was identical to that of control viruses in the HSP72-negative cell line Y3.Ag.1.2.3, and overexpression of HSP72 had no effect on the virulence of VV infection in normal or immunocompromised mice. We conclude that while VV infection results in the induction of the major inducible 72-kDa HSP, VV replication proceeds normally in the absence of this protein. It is unclear whether another celluar chaperone is required to facilitate virus replication in place of HSP72 in Y3.Ag.1.2.3 cells or whether HSP expression plays no role in virus replication, but is simply a component of the generalized stress response to virus infection.

Animals↗
PubMed1989

Mouse fetal thymus lobes cultured in IL-2 generate CD3+, TCR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- cells.

Whole, undisrupted, 14-day fetal mouse thymus lobes were liquid-cultured in medium supplemented with 10 U/ml rIL-2. The cells that emerged from these fetal thymus lobes grew in an IL-2-dependent manner and showed non-MHC-restricted cytolytic activity. By two-color flow microfluorimetric analysis they could be subdivided into CD4-/CD8+ and CD4-/CD8- subpopulations, both of which contained CD3+ cells. Northern analysis of total cellular RNA revealed full-length transcripts of gamma- and delta-message, predominantly the truncated (1.0 kb) beta- and no detectable alpha-message. Taken together, these results show that by culturing 14-day fetal thymus lobes in IL-2, in the absence of deliberate mitogen stimulation, CD3+, TcR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- T cells are obtained. Such cells may represent the precursors of similar cells found outside the thymus in adult mice.

Animals↗