scholarly journals High-Resolution Quantitative Mapping of Macaque Cervicovaginal Epithelial Thickness: Implications for Mucosal Vaccine Delivery

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathleen L. Vincent ◽  
Patrice A. Frost ◽  
Massoud Motamedi ◽  
Edward J. Dick ◽  
Jingna Wei ◽  
...  

Vaginal mucosal surfaces naturally offer some protection against sexually transmitted infections (STIs) including Human Immunodeficiency Virus-1, however topical preventative medications or vaccine designed to boost local immune responses can further enhance this protection. We previously developed a novel mucosal vaccine strategy using viral vectors integrated into mouse dermal epithelium to induce virus-specific humoral and cellular immune responses at the site of exposure. Since vaccine integration occurs at the site of cell replication (basal layer 100-400 micrometers below the surface), temporal epithelial thinning during vaccine application, confirmed with high resolution imaging, is desirable. In this study, strategies for vaginal mucosal thinning were evaluated noninvasively using optical coherence tomography (OCT) to map reproductive tract epithelial thickness (ET) in macaques to optimize basal layer access in preparation for future effective intravaginal mucosal vaccination studies. Twelve adolescent female rhesus macaques (5-7kg) were randomly assigned to interventions to induce vaginal mucosal thinning, including cytobrush mechanical abrasion, the chemical surfactant spermicide nonoxynol-9 (N9), the hormonal contraceptive depomedroxyprogesterone acetate (DMPA), or no intervention. Macaques were evaluated at baseline and after interventions using colposcopy, vaginal biopsies, and OCT imaging, which allowed for real-time in vivo visualization and measurement of ET of the mid-vagina, fornices, and cervix. P value ≤0.05 was considered significant. Colposcopy findings included pink, rugated tissue with variable degrees of white-tipped, thickened epithelium. Baseline ET of the fornices was thinner than the cervix and vagina (p<0.05), and mensing macaques had thinner ET at all sites (p<0.001). ET was decreased 1 month after DMPA (p<0.05) in all sites, immediately after mechanical abrasion (p<0.05) in the fornix and cervix, and after two doses of 4% N9 (1.25ml) applied over 14 hrs in the fornix only (p<0.001). Histological assessment of biopsied samples confirmed OCT findings. In summary, OCT imaging allowed for real time assessment of macaque vaginal ET. While varying degrees of thinning were observed after the interventions, limitations with each were noted. ET decreased naturally during menses, which may provide an ideal opportunity for accessing the targeted vaginal mucosal basal layers to achieve the optimum epithelial thickness for intravaginal mucosal vaccination.

2020 ◽  
Vol 6 (1) ◽  
pp. 00171-2019 ◽  
Author(s):  
Ronja Weber ◽  
Naemi Haas ◽  
Astghik Baghdasaryan ◽  
Tobias Bruderer ◽  
Demet Inci ◽  
...  

Early pulmonary infection and inflammation result in irreversible lung damage and are major contributors to cystic fibrosis (CF)-related morbidity. An easy to apply and noninvasive assessment for the timely detection of disease-associated complications would be of high value. We aimed to detect volatile organic compound (VOC) breath signatures of children with CF by real-time secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS).A total of 101 children, aged 4–18 years (CF=52; healthy controls=49) and comparable for sex, body mass index and lung function were included in this prospective cross-sectional study. Exhaled air was analysed by a SESI-source linked to a high-resolution time-of-flight mass spectrometer. Mass spectra ranging from m/z 50 to 500 were recorded.Out of 3468 m/z features, 171 were significantly different in children with CF (false discovery rate adjusted p-value of 0.05). The predictive ability (CF versus healthy) was assessed by using a support-vector machine classifier and showed an average accuracy (repeated cross-validation) of 72.1% (sensitivity of 77.2% and specificity of 67.7%).This is the first study to assess entire breath profiles of children with SESI-HRMS and to extract sets of VOCs that are associated with CF. We have detected a large set of exhaled molecules that are potentially related to CF, indicating that the molecular breath of children with CF is diverse and informative.


2007 ◽  
Vol 75 (10) ◽  
pp. 4917-4922 ◽  
Author(s):  
Catherine P. A. Ivory ◽  
Kris Chadee

ABSTRACT The development of an effective amebiasis vaccine could improve child health in the developing world, reducing cases of amebic colitis and liver abscess. An ideal vaccine would be comprised of a well-characterized parasite antigen and an adjuvant, which would have high potency while driving the immune response in a Th1 direction. This study describes a mucosal vaccine composed of the Entamoeba histolytica galactose/N-acetyl-d-galactosamine-inhibitable lectin (Gal-lectin) and CpG oligodeoxynucleotides (CpG-ODN). The Gal-lectin is a protein involved in parasite virulence and adherence and is known to activate immune cells, while CpG-ODN are known to be potent inducers of type 1-like immune responses. We demonstrated that intranasal administration of the vaccine resulted in strong Gal-lectin-specific Th1 responses and humoral responses. Vaccination induced the production of Gal-lectin-specific T cells and the production of the proinflammatory cytokine gamma interferon. Vaccinated animals had detectable serum anti-Gal-lectin immunoglobulin G (IgG) and stool anti-Gal-lectin IgA capable of blocking parasite adherence to target cells in vitro. One week after immunization, gerbils were challenged intrahepatically with live trophozoites. Vaccinated gerbils had no detectable abscesses after day 5, whereas control gerbils developed larger abscesses. These results show that mucosal vaccination with Gal-lectin and CpG-ODN can induce both systemic and humoral immune responses.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246422
Author(s):  
Rui Tada ◽  
Miki Ogasawara ◽  
Daisuke Yamanaka ◽  
Yasuhiro Sakurai ◽  
Yoichi Negishi ◽  
...  

Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.


Author(s):  
Kenneth Krieg ◽  
Richard Qi ◽  
Douglas Thomson ◽  
Greg Bridges

Abstract A contact probing system for surface imaging and real-time signal measurement of deep sub-micron integrated circuits is discussed. The probe fits on a standard probe-station and utilizes a conductive atomic force microscope tip to rapidly measure the surface topography and acquire real-time highfrequency signals from features as small as 0.18 micron. The micromachined probe structure minimizes parasitic coupling and the probe achieves a bandwidth greater than 3 GHz, with a capacitive loading of less than 120 fF. High-resolution images of submicron structures and waveforms acquired from high-speed devices are presented.


Author(s):  
Yuefeng Wang ◽  
Kuang Mao ◽  
Tong Chen ◽  
Yanglong Yin ◽  
Shuibing He ◽  
...  

2021 ◽  
Vol 20 (3) ◽  
pp. 1-22
Author(s):  
David Langerman ◽  
Alan George

High-resolution, low-latency apps in computer vision are ubiquitous in today’s world of mixed-reality devices. These innovations provide a platform that can leverage the improving technology of depth sensors and embedded accelerators to enable higher-resolution, lower-latency processing for 3D scenes using depth-upsampling algorithms. This research demonstrates that filter-based upsampling algorithms are feasible for mixed-reality apps using low-power hardware accelerators. The authors parallelized and evaluated a depth-upsampling algorithm on two different devices: a reconfigurable-logic FPGA embedded within a low-power SoC; and a fixed-logic embedded graphics processing unit. We demonstrate that both accelerators can meet the real-time requirements of 11 ms latency for mixed-reality apps. 1


Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zhicheng Xiao ◽  
Andrea Alù

Abstract Fano resonances feature an asymmetric lineshape with controllable linewidth, stemming from the interplay between bright and dark resonances. They provide efficient opportunities to shape the scattering lineshape, but they usually lack flexibility and tunability and are hindered by loss in passive systems. Here, we explore a hybrid parity-time (PT) and anti-parity-time (APT) symmetric system supporting unitary scattering features with highly tunable Fano resonances. The PT-APT-symmetric system can be envisioned in nanophotonic and microwave circuit implementations, allowing for real-time control of the scattering lineshape and its underlying singularities. Our study shows the opportunities enabled by non-Hermitian platforms to control scattering lineshapes for a plethora of photonic, electronic, and quantum systems, with potential for high-resolution imaging, switching, sensing, and multiplexing.


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