1,721,148 research outputs found
Vaccines containing the HIV tat protein as an adjuvant for the enhancement of cytotoxic T-cell responses
No full textThe HIV-1 Tat modifies the catalytic subunit composition and activity of immunoproteasomes in B and T cells which either express Tat, or have been treated with biologically active exogenous Tat protein. This results in modulation of the in vitro CTL epitope hierarchy. In particular, both intracellularly expressed and exogenous native Tat protein increase the major proteolytic activities of the proteasome by up-regulating LMP7 and MECL1 subunits and by down-modulating the LMP2 subunit. This results in a more efficient generation and presentation of subdominant CTL epitopes (Gavioli et al. J. Immunol, 2004, 173:3838-3843 and Patent No. 0323840.9). Since the amount of MHC-I/epitope complexes is crucial in determining the presence and the strength of epitope-specific CTL responses, we set out to verify the biological relevance of these findings for vaccination strategies by evaluating epitope-specific CTL responses against ovalbumin in mice vaccinated with ovalbunin alone, or with ovalbumin in combination with Tat. We found that Tat slightly decreases CTL responses directed to the immunodominant epitope, while it induces those directed to subdominant and cryptic T-cell epitopes which were absent in mice vaccinated with ovalbumin alone (Patent No. 0323840.9). This finding suggests that Tat favours the generation of CTL responses directed to “weak” CTL epitopes and could therefore be used as a tool to increase CTL responses to heterologous antigens.
In addition, we found that a mutated form of the HIV-1 Tat protein, carrying glycine instead of cysteine 22 (Tatcys22), like wild-type Tat, modifies the subunit composition of proteasomes. Tatcys22 mutant, in contrast to wild-type Tat, has no effect on the transactivation of the HIV-1 LTR, and does not induce reactivation of latent infection.
We also demonstrated that peptide 47-86, derived from the wild-type Tat protein, is sufficient to down-modulate the LMP2 subunit.
Therefore, mutated forms of Tat, or Tat-derived peptides, may represent an important alternative to the use of wild-type Tat in vaccination strategies aimed at increasing epitope-specific T cell responses directed to heterologous antigens.
We exploited the effect in vivo of wild-type Tat protein and mutant Tatcys22 protein on T cell responses against structural HIV gene products. To this end, Balb/C mice were immunized with HIV-1 Gag or Env protein antigens, either alone or in combination with wild-type Tat or mutant Tatcys22. We found that both wild-type Tat and mutated Tatcys22 increase the number of epitope-specific T cell responses against Gag and Env antigens. In particular, we demonstrated that mice vaccinated with Gag, in combination with wild-type Tat or with the mutant Tatcys22, responded to 7 or 11 T cell Gag-derived epitopes respectively, in contrast to mice vaccinated with Gag alone, which responded to 4 T cell Gag-derived epitopes. Similarly, mice vaccinated with Env, in combination with wild-type Tat or with the mutant Tatcys22 responded to 12 Env-derived pools of epitopes, in contrast to mice vaccinated with Env alone, which responded to 8 T cell Env-derived peptide pools.
These observations, together with our previous findings, suggest that Tat is not only an antigen but also a novel adjuvant capable of increasing T cell responses against heterologous antigens. Therefore, the Tat protein, as well as mutant Tatcys22, may represent an important tool in HIV-1 vaccine strategies aimed at broadening the spectrum of the epitopes recognized by T cells
Constitutive expression of HIV-1 tat protein in human Jurkat T cells using a BK virus vector.
No full textThe production and characterization of Jurkat cell lines that constitutively express functional human immune deficiency virus type 1 (HIV-1) tat protein, using a BK virus plasmid expression vector and HIV-1 tat cDNA, is described. An increased growth rate of these Jurkat-tat cell lines as compared with control cell lines was observed
Reexamination of the coding potential of the HTLV-1 pX region.
No full textThe human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia (ATL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In addition to tax and rex genes eight additional open reading frames are present in the pX region of HTLV-1. The possibility that these open reading frames can encode a protein in human cell lines persistently infected by HTLV-1 or in COS-1 cells transfected with a pX expressor plasmid was investigated. The results presented here indicate that tax and rex are the only proteins detected. Moreover, antibodies against proteins in vitro translated by five of the additional open reading frames of the pX region were not found in sera of ATL and TSP/HAM patients, further indicating that those proteins are not usually made in infected cells
Vaccines (United Kingdom Patent application)
No full textFIELD OF THE INVENTION
The present invention relates to vaccines comprising Tat, biologically active derivatives thereof or precursors therefor, including nucleic acids encoding such, as well as to methods for vaccination comprising the use of such vaccines
Functional polymeric nano/microparticles for protein and DNA vaccine delivery.
No full textThe use of particulate polymeric carriers holds great promise for the development of effective and affordable DNA and protein subunit vaccines. Rational development of such vaccine formulations requires a detailed understanding of their physico-chemical properties, cell-free and in vitro behaviour, in addition to particle uptake and processing mechanisms to antigen presenting cells capable of stimulating safe and effective immune responses. We here provide an overview on functional polymeric nano- and micro-particles designed for surface adsorption of proteins and DNA antigens currently under investigation for the formulation of new vaccines, including comments on their preparation method, antigen delivery strategy, cell-free and in vitro behaviour. In addition, we focus on their influence in activating antigen-specific humoral and/or cellular immune responses and on their potential for the development of new vaccines
Recombinant herpes simplex virus and uses therefor
No full text(WO200592374)
Provided is a replication-deficient HSV encoding a heterologous antigen, and a vaccine comprising the HSV.The vaccine
may be directed to viruses, intracellular bacteria or tumours.Also provided is an anticancer vaccine comprising
replication-deficient HSV encoding an angiogenesis inhibitor, a cytokine and a suicide gene.A challenge model for
screening candidate antigens is also provided, as is an UL13 mutant HSV vector.Further provided are HSV vectors for
expression of Hex A and NTFs, and methods comprising said HSV
Transactivation of BKV and SV40 early promoters by BKV and SV40 T-antigens.
No full textThe early promoters of BKV and SV40 plasmids were transactivated in both BKV and SV40-transformed cells which failed to support replication of these plasmids. This suggests that the T-antigen of either virus can transactivate BKV and SV40 early promoters by either increasing the availability of cellular transcription factors or by directly interacting with specific sequences which comprise the transcriptional control region of the early promoters. We also observed that removal of 8-bp on the early side of T-antigen binding site I of BKV does not alter viral-plasmid replication
Transactivation of BKV and SV40 early promoters by BKV and SV40 T-antigens
No full textThe early promoters of BKV and SV40 plasmids were transactivated in both BKV and SV40-transformed cells which failed to support replication of these plasmids. This suggests that the T-antigen of either virus can transactivate BKV and SV40 early promoters by either increasing the availability of cellular transcription factors or by directly interacting with specific sequences which comprise the transcriptional control region of the early promoters. We also observed that removal of 8-bp on the early side of T-antigen binding site I of BKV does not alter viral-plasmid replication. © 1986
- …
