Microbiology & Immunology - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/226

Filters

2018 - 2019 2
2
Reset filters

Settings
Statistics
Citations
Author: De Rose, Robert × Author: Glass, Joshua Julian × Author: Kent, Stephen × Author: Wheatley, Adam ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime-boost immunization
    Tan, H-X ; Wheatley, AK ; Esterbauer, R ; Jegaskanda, S ; Glass, JJ ; Masopust, D ; De Rose, R ; Kent, SJ (NATURE PUBLISHING GROUP, 2018-05)
    Tissue-resident memory (TRM) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 TRM cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 TRM cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 TRM cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 TRM cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 TRM cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.
  • Item
    Thumbnail Image
    Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies
    Cui, J ; Ju, Y ; Houston, ZH ; Class, JJ ; Fletcher, NL ; Alcantara, S ; Dai, Q ; Howard, CB ; Mahler, SM ; Wheatley, AK ; De Rose, R ; Brannon, PT ; Paterson, BM ; Donnelly, PS ; Thurecht, K ; Caruso, F ; Kent, SJ (WILEY, 2019-05)
    Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.