IgE and IgG4 epitopes of the peanut allergens shift following oral immunotherapy.

Background: Oral immunotherapy (OIT) with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants. Objective: Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants (n = 20) enrolled in phase 3 PTAH OIT clinical trials. Methods: Pre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays. IgE and IgG4 linear epitopes were identified based on binding to synthetic overlapping 15-mer linear peptides of 10 peanut allergens (Ara h 1-11) synthesized on microarray slides. Results: Statistically significant decreases in IgE binding were identified for intact Ara h 2, 3, and 6, and known and newly identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with most linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the IgE and IgG4 binding ratios and intensity are altered. Conclusion: At a population level, the linear IgE and IgG4 epitopes of 10 peanut allergens overlap and that increase in IgG4 with OIT results in displacement of IgE binding to both conformational and linear epitopes. Furthermore, it appears as though the increase in IgG4 is more important to achieve desensitization at the 12-month timepoint than the decrease in IgE. This type of knowledge can be useful in the identification of IgE and IgG4-binding allergen and peptide biomarkers that may indicate desensitization or sustained unresponsiveness of allergic individuals to peanut.

Investigation of Amphiphilic Polypeptoid-Functionalized Halloysite Nanotubes as Emulsion Stabilizer for Oil Spill Remediation.

Halloysite nanotubes (HNTs), naturally occurring and environmental benign clay nanoparticles, have been successfully functionalized with amphiphilic polypeptoid polymers by surface-initiated polymerization methods and investigated as emulsion stabilizers toward oil spill remediation. The hydrophilicity and lipophilicity balance (HLB) of the grafted polypeptoids was shown to affect the wettability of functionalized HNTs and their performance as stabilizers for oil-in-water emulsions. The functionalized HNTs having relatively high hydrophobic content (HLB = 12.0-15.0) afforded the most stable oil-in-water emulsions containing the smallest oil droplet sizes. This has been attributed to the augmented interfacial activities of polypeptoid-functionalized HNTs, resulting in more effective reduction of interfacial tension, enhancement of thermodynamic propensity of the HNT particles to partition at the oil-water interface, and increased emulsion viscosity relative to the pristine HNTs. Cell culture studies have revealed that polypeptoid-functionalized HNTs are noncytotoxic toward Alcanivorax borkumensis, a dominant alkane degrading bacterium found in the ocean after oil spill. Notably, the functionalized HNTs with higher hydrophobic polypeptoid content (HLB = 12.0-14.3) were shown to induce more cell proliferation than either pristine HNTs or those functionalized with less hydrophobic polypeptoids. It was postulated that the functionalized HNTs with higher hydrophobic polypeptoid content may promote the bacterial proliferation by providing larger oil-water interfacial area and better anchoring of bacteria at the interface.

Mesenchymal stem cells are attracted to latent HIV-1-infected cells and enable virus reactivation via a non-canonical PI3K-NFκB signaling pathway.

Persistence of latent HIV-1 in macrophages (MACs) and T-helper lymphocytes (THLs) remain a major therapeutic challenge. Currently available latency reversing agents (LRAs) are not very effective in vivo. Therefore, understanding of physiologic mechanisms that dictate HIV-1 latency/reactivation in reservoirs is clearly needed. Mesenchymal stromal/stem cells (MSCs) regulate the function of immune cells; however, their role in regulating virus production from latently-infected MACs & THLs is not known. We documented that exposure to MSCs or their conditioned media (MSC-CM) rapidly increased HIV-1 p24 production from the latently-infected U1 (MAC) & ACH2 (THL) cell lines. Exposure to MSCs also increased HIV-1 long terminal repeat (LTR) directed gene expression in the MAC and THL reporter lines, U937-VRX and J-Lat (9.2), respectively. MSCs exposed to CM from U1 cells (U1-CM) showed enhanced migratory ability towards latently-infected cells and retained their latency-reactivation potential. Molecular studies showed that MSC-mediated latency-reactivation was dependent upon both the phosphatidyl inositol-3-kinase (PI3K) and nuclear factor-κB (NFκB) signaling pathways. The pre-clinically tested inhibitors of PI3K (PX-866) and NFκB (CDDO-Me) suppressed MSC-mediated HIV-1 reactivation. Furthermore, coexposure to MSC-CM enhanced the latency-reactivation efficacy of the approved LRAs, vorinostat and panobinostat. Our findings on MSC-mediated latency-reactivation may provide novel strategies against persistent HIV-1 reservoirs.

Bacterial proliferation on clay nanotube Pickering emulsions for oil spill bioremediation.

Halloysites (tubular aluminosilicate) are introduced as inexpensive natural nanoparticles that form and stabilize oil-water emulsions. Pickering emulsification can proceed with energies low enough to be afforded by ocean turbulence and the stability of droplets extends over more than a week. The oil/water interface is shown to be roughened and bacteria, which are added for oil degradation, are better attached to such oil droplets than to droplets without halloysites. The metabolic activity of Alcanivorax borkumensis, alkanotrophic bacteria widely distributed in marine environments, is enhanced by halloysite addition. A halloysite-based dispersant system is therefore environmentally friendly and promising for further optimization. The key elements of the described formulations are natural clay nanotubes, which are abundantly available in thousands of tons, thus making this technology scalable for environmental remediation.