| 1. |
|
|
| 2. |
- Koopman, G, et al.
(författare)
-
Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian-human immunodeficiency virus viraemia with protein/DNA combination
- 2008
-
Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 89:Pt 2, s. 540-553
-
Tidskriftsartikel (refereegranskat)abstract
- Current data suggest that prophylactic human immunodeficiency virus type 1 (HIV) vaccines will be most efficacious if they elicit a combination of adaptive humoral and T-cell responses. Here, we explored the use of different vaccine strategies in heterologous prime–boost regimes and evaluated the breadth and nature of immune responses in rhesus monkeys induced by epidermally delivered plasmid DNA or recombinant HIV proteins formulated in the AS02A adjuvant system. These immunogens were administered alone or as either prime or boost in mixed-modality regimes. DNA immunization alone induced cell-mediated immune (CMI) responses, with a strong bias towards Th1-type cytokines, and no detectable antibodies to the vaccine antigens. Whenever adjuvanted protein was used as a vaccine, either alone or in a regime combined with DNA, high-titre antibody responses to all vaccine antigens were detected in addition to strong Th1- and Th2-type CMI responses. As the vaccine antigens included HIV-1 Env, Nef and Tat, as well as simian immunodeficiency virus (SIV)mac239 Nef, the animals were subsequently exposed to a heterologous, pathogenic simian–human immunodeficiency virus (SHIV)89.6p challenge. Protection against sustained high virus load was observed to some degree in all vaccinated groups. Suppression of virus replication to levels below detection was observed most frequently in the group immunized with protein followed by DNA immunization, and similarly in the group immunized with DNA alone. Interestingly, control of virus replication was associated with increased SIV Nef- and Gag-specific gamma interferon responses observed immediately following challenge.
|
|
| 3. |
|
|
| 4. |
- Saltel, F, et al.
(författare)
-
New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control beta3-integrin clustering
- 2009
-
Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 187:5, s. 715-731
-
Tidskriftsartikel (refereegranskat)abstract
- Integrin-dependent adhesion sites consist of clustered integrins that transmit mechanical forces and provide signaling required for cell survival and morphogenesis. Despite their importance, the regulation of integrin clustering by the cytoplasmic adapter protein talin (Tal) and phosphatidylinositol (PI)-4,5-biphosphate (PI(4,5)P2) lipids nor their dynamic coupling to the actin cytoskeleton is fully understood. By using a Tal-dependent integrin clustering assay in intact cells, we identified a PI(4,5)P2-binding basic ridge spanning across the F2 and F3 domains of the Tal head that regulates integrin clustering. Clustering requires a new PI(4,5)P2-binding site in F2 and is negatively regulated by autoinhibitory interactions between F3 and the Tal rod (Tal-R). The release of the Tal-R exposes a new β3-integrin–binding site in F3, enabling interaction with a membrane proximal acidic motif, which involves the formation of salt bridges between K316 and K324 with E726 and D723, respectively. This interaction shields the β-integrin tail from reassociation with its α subunit, thereby maintaining the integrin in a substrate-binding and clustering-competent form.
|
|
