274 research outputs found
Improving vaccine equity with novel technology platforms
No full textThe goal of global vaccine equity, the idea that vaccines should be allocated across all countries based on needs rather than economic status, comes across as a goal that everyone can agree on. The emergence of a global pandemic gave clarity to how constrained our vaccination methods currently are, shining a blinding light of realism on how out of reach our objective of global vaccine equity may be. If we are to continue with our current methods of vaccine development and distribution, standard intramuscular injection, this recurring global vaccine inequity crisis will likely prevail.
To address the inefficiencies of today’s approach toward global vaccination, we propose a new approach. Our thesis is that the solution to this global vaccine inequity crisis is new technology. Here, we propose to improve vaccine equity using novel technology platforms, specifically through the emerging biotechnology and key attributes of the microneedle array patch.
As a collective, the outline for this thesis is as follows: First, it is necessary to establish that there is a problem of vaccination inequity around the world. More so, though our current methods for global vaccine administration are not entirely ineffective, they fall short of fulfilling the need for global vaccine equity. After this has been established, we will analyze why it is necessary to take the risk in pivoting to a novel vaccination strategy, via dissolvable microneedle array patch delivery, as opposed to continuing our current strategy: why it is necessary to change what we are doing now. Then, we will support the argument for change by describing the technology and benefits it enables, the rationale for the vaccination approach, and preliminary studies that support feasibility. Together, we present the ethical, public health, technical, and scientific basis for a new focus on emerging technology to address global vaccine equity, and how this strategic shift can work
“Toll”-erance in the Skin
No full textInteractions between potentially pathogenic commensal bacteria and cutaneous immunity are poorly understood. In this issue of Immunity, Skabytska et al. (2014) show that S. aureus-derived TLR2/6 heterodimer ligands can recruit myeloid-derived suppressor cells into the skin, countering rather than promoting inflammation
Epidermal Dendritic Cells Induce Potent Antigen-Specific CTL-Mediated Immunity
No full textProfessional antigen-presenting cells (APCs) are required for the initiation of an immune response. Dendritic cells (DCs) are the most potent APCs identified thus far and can present antigen in the context of co-stimutatory signals required for the stimulation of both primed and naïve T cells. Cytotoxic T lymphocytes (CTLs) are critical to the immune response against tumors or virally infected cells. Optimal stimulation of antigen-specific CTLs is the goal of evolving immunization strategies for the prevention or therapy of viral infections and tumors. Epidermal dendritic cells (eDCs), or Langerhans cells, can present antigens for the stimulation of CD4+ T cell dependent anti-tumor immunity and may play a role in tumor surveillance. The capacity of eDCs to induce tumor-specific CD88 CTL immunity has not been determined. We have previously shown that DCs derived from bone marrow precursors (BmDCs) under the influence of cytokines can induce protective, antigen-specific CTL-mediated anti-tumor immunity. Here we show that subcutaneous immunization with ovalbumin (OVA) peptide (SIINFEKL257–264)-pulsed eDCs induced OVA-specific, CD8+ CTLs that lyse the OVA-expressing target. Furthermore, mice vaccinated with OVA peptide–pulsed eDCs were completely protected from subsequent challenge by the OVA-expressing melanoma MOS. The capacity of peptide-pulsed eDCs to induce CTL-mediated immunity is directly dependent on the dose of eDCs administered. Importantly, the APC capacity of eDCs is comparable to that of BmDCs, as mice immunized with eDC populations containing at least as many class II+/B7.2+ cells as populations of BmDCs were equally protected against challenge with MO5. These results demonstrate that eDCs can be potent inducers of antigen-specific CD8+ CTL-mediated immunity. They suggest that eDCs may be important targets for antigen delivery strategies aimed at inducing anti-viral or anti-tumor immunity
Knockdown of HMGB1 in Tumor Cells Attenuates Their Ability To Induce Regulatory T Cells and Uncovers Naturally Acquired CD8 T Cell-Dependent Antitumor Immunity
No full textAbstract
Although high mobility group box 1 (HMGB1) in tumor cells is involved in many aspects of tumor progression, its role in tumor immune suppression remains elusive. Host cell-derived IL-10 suppressed a naturally acquired CD8 T cell-dependent antitumor response. The suppressive activity of tumor-associated Foxp3+CD4+CD25+ regulatory T cells (Treg) was IL-10 dependent. Neutralizing HMGB1 impaired tumor cell-promoted IL-10 production by Treg. Short hairpin RNA-mediated knockdown of HMGB1 (HMGB1 KD) in tumor cells did not affect tumor cell growth but uncovered naturally acquired long-lasting tumor-specific IFN-γ– or TNF-α–producing CD8 T cell responses and attenuated their ability to induce Treg, leading to naturally acquired CD8 T cell- or IFN-γ–dependent tumor rejection. The data suggest that tumor cell-derived HMGB1 may suppress naturally acquired CD8 T cell-dependent antitumor immunity via enhancing Treg to produce IL-10, which is necessary for Treg-mediated immune suppression.</jats:p
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