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Project description:Dithranol as novel co-adjuvant for non-invasive dermal vaccination
| PRJNA781116 | ENA
Project description:Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC(50) values correlated with estimated in vivo growth rates.
| S-EPMC3105089 | biostudies-literature
Project description:The use of an immunologic adjuvant to augment the immune response is essential for modern vaccines which are relatively ineffective on their own. In the past decade, researchers have been consistently reporting that skin treatment with a physical parameter, namely laser light, augments the immune response to vaccine and functions as an immunologic adjuvant. This "laser adjuvant" has numerous advantages over the conventional chemical or biological agents; it is free from cold chain storage, hypodermic needles, biohazardous sharp waste, irreversible formulation with vaccine antigen, undesirable biodistribution in vital organs, or unknown long-term toxicity. Since vaccine formulations are given to healthy populations, these characteristics render the "laser adjuvant" significant advantages for clinical use and open a new developmental path for a safe and effective vaccine. In addition, laser technology has been used in the clinic for more than three decades and is therefore technically matured and has been proved to be safe. Currently, four classes of laser adjuvant have been reported; ultrashort pulsed, non-pulsed, non-ablative fractional, and ablative fractional lasers. Since each class of the laser adjuvant shows a distinct mechanism of action, a proper choice is necessary to craft an effective vaccine formulation toward a desired clinical benefit for a clinical vaccine to maximize protection. In addition, data also suggest that further improvement in the efficacy is possible when a laser adjuvant is combined with chemical or biological adjuvant(s). To realize these goals, further efforts to uncover the molecular mechanisms of action of the laser adjuvants is warranted. This review provides a summary and comments of the recent updates in the laser adjuvant technology.
| S-EPMC7060115 | biostudies-literature
Project description:Here, we analyse two SE strains, an infectious bovine strain PM221 isolated from persistent subclinical bovine IMI, and ATCC12228 representing a low-infectious human skin strain, on total proteome level.
2014-06-10 | PXD000404 | Pride
Project description:After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.
2024-07-24 | GSE241235 | GEO
Project description:normal skin (no), actinic keratosis (ak), and squamous cell carcinoma (scc) of the skin were examined: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. The type and number of genes involved in non-melanoma skin cancer (NMSC) are still unclear. This study examined and identified different expressed genes in NMSC. Fifteen snap-frozen biopsies of five immunosuppressed organ-transplanted recipients each normal skin, actinic keratosis (AK) and invasive squamous cell carcinoma (SCC) were analysed. Total RNA was extracted reverse transcribed and biotin-labeled cRNA was used for hybridization with Affymetrix HG-U133A gene expression cDNA-microarrays containing 22,283 known genes. Confocal scanner evaluated the signals twice and data analysis was performed by predicition analysis of microarrays (PAM) using nearest shrunken centroids with the threshold 3.5 to identify genes best characterizing normal skin and skin cancer. ANOVA analysis was performed as a second independent method to identify differentially expressed genes (p<0.05, and p<0.15). Quantitative verification of 13 up- or down-regulated genes was performed by real-time RT-PCR and genes were confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes. Some of the genes (e.g. annexin, lamin, and metalloproteinases) up-regulated in carcinomas in our study have previously reported as over-expressed in NMSC. In total 42 genes were up-regulated and 76 genes were down-regulated in non-melanoma skin cancer. The majority of genes identified have not been previously reported different expressed during non-melanoma skin carcinogenesis. Keywords: ordered
2006-06-30 | GSE2503 | GEO
Project description:Use of tape stripping for the collection of stratum corneum is a versatile and reliable procedure for the evaluation of the human skin health, including assessments of the skin barrier function, microbial content, and disease biomarkers. The tape stripping procedure is widely referenced; however, the number and type of tapes required for sample collection vary considerably, and the lack of standardized sampling, processing and normalization protocols complicate data comparison and interpretation. We have compared the performances of two commonly used non-invasive skin sampling platforms by collecting skin tissue from 34 healthy volunteers and applying standardization throughout the workflow, from sampling to data analysis. Our results showed significant differences in the amounts of tissue collected per tape, erythema levels, RNA and protein yields. RNA extracts from both platforms were suitable for sequencing; comparable input and quality of reads were produced for both test groups, however significant differences were found in the percentage of uniquely mapped reads and detected genes. This data highlights processing optimization as an important step in maximizing the efficiency of biomolecule extraction from tape strips and further presents a tape stripping method suitable for fast, efficient, and non-invasive epidermal tissue collection applicable to skin biomarker discovery.
2024-04-24 | GSE262827 | GEO
Project description:Melanoma is a very aggressive type of skin cancer, which renders it difficult to treat because of extensive heterogeneity frequently observed in melanoma tumours. Here we hypothesized that gene expression and DNA methylation differences would correlate with invasiveness in melanoma cells. To address this question, we carried out genome-wide transcriptome and methylome investigations in non-invasive and invasive groups of melanoma cell lines.
2021-04-06 | GSE153594 | GEO
Project description:Melanoma is a very aggressive type of skin cancer, which renders it difficult to treat because of extensive heterogeneity frequently observed in melanoma tumours. Here we hypothesized that gene expression and DNA methylation differences would correlate with invasiveness in melanoma cells. To address this question, we carried out genome-wide transcriptome and methylome investigations in non-invasive and invasive groups of melanoma cell lines.
2021-04-06 | GSE153592 | GEO
Project description:This study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of 61 histopathologically diagnosed Keratinocytic skin lesions (KSLs), including pre-malignant actinic keratosis (AK) and Bowen's disease (BD), and invasive cutaneous squamous cell carcinoma (cSCC)as well as matched normal stratum corneum samples collected from 26 patients.
2024-05-01 | PXD041905 | JPOST Repository