Intradermal Research Articles

Noninvasive Needle‐Free Cancer Vaccine Cream Patch Based on Fluorinated Chitosan

AbstractIn recent years, cancer vaccines that intend to specifically initiate host immune responses against cancer have achieved some clinical success. Delivery of vaccines with traditional needles is usually associated with the risk of infection and poor patient compliance. The development of needle‐free vaccines may overcome these limitations. In this work, a needle‐free patch is designed for effective cancer vaccination using a fluorine chain‐modified cationic polymer, fluorinated chitosan (FCS), which is able to transdermatically deliver the antigen to antigen‐presenting cells in the skin. Specifically, a transdermal carrier, FCS, and model antigen ovalbumin (OVA) can self‐assemble into nanoparticles, which can reversibly open the tight junction‐associated proteins of epithelial cells and penetrate across the epidermis. The needle‐free cancer vaccine patch is fabricated by mixing FCS‐OVA nanoparticles with the US Food and Drug Administration‐approved immune adjuvant imiquimod (R837) in blank cream. Such a needle‐free cancer vaccine can generate robust immune responses to protect mice against ovalbumin‐expressing melanoma (B16‐OVA). Compared to traditional intradermal injection, needle‐free cancer vaccines achieved an even more efficient protection effect against B16‐OVA cancer cells. This work indicated that the novel needle‐free cancer vaccine may provide a compelling technology for simple and safe vaccination, which may help to increase vaccination coverage.

Study of effect of topical mometasone with intralesional platelet-rich plasma versus topical mometasone alone in the treatment of alopecia areata

Background: Alopecia areata (AA) is an autoimmune disorder and exhibits non scarring alopecia. Currently, there is no definitive cure, platelet rich plasma (PRP) has emerged as a newer modality for non-cicatricial alopecias such as AA. This study was conducted to compare the efficacy and adverse effects of topical mometasone with PRP versus topical mometasone alone in the treatment of patients of AA. Methods: This study was conducted on a total of 100 clinically diagnosed cases of AA. Patients in group A were subjected to intradermal injection of autologous PRP every 3 weeks along with topical mometasone cream 0.1% daily for 12 weeks. Group B was treated with topical mometasone cream 0.1% once a day locally over affected site for 12 weeks. Results: Baseline SALT score of group A was 6.05±5.36 while that of group B was 6.62±4.39. The mean SALT score of group A declined to 0.94±1.69 and that of group B 2.19±1.76 over a period of 20 weeks. Excellent response was observed by 12 and 5 patients of group A and group B respectively. Minor side effects like pain was seen in 10 patients (20%) in group A, while atrophy was seen in 2 patients of group B. Conclusions: This is the first ever study evaluating the additional benefit of intralesional PRP. In this study, it was found that adding intralesional PRP with topical mometasone 0.1% cream has higher efficacy and early improvement than topical mometasone alone, in the treatment of AA.

Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study

Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n=10 each) or vehicle-GNP (LD or HD, n=3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90,+0.0318%, 95% CI: 0.0088-0.1723, p=0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35,+0.8/105 CD8+, 95% CI: 0.19-5.13, p=0.014 and +1.34/105 CD8+, 95% CI: 0.1-7.34, p=0.024, respectively). Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. Emergex Vaccines Holding Limited.

Exploring the potential of intradermal platelet-rich plasma in treating acquired bilateral nevus of Ota-like macule (Hori's nevus): A pilot study.

Hori's nevus is a common and challenging dermatological condition, often complicated by post-inflammatory hyperpigmentation following treatment. Platelet-rich plasma (PRP) has demonstrated efficacy in the treatment of hyperpigmentation disorders such as melasma and periorbital darkening. Given the benefits and minimally invasive nature of PRP treatments, exploring its application in managing Hori's nevus through further investigation is worthwhile. To evaluate the safety and effectiveness of intradermal PRP therapy for the treatment of Hori's nevus. Ten female patients received bilateral intradermal PRP injections every 2 weeks for a total of four treatments. The modified dermal pigmentation and severity index (mDPASI), mean melanin index (MI), brightening score, patient self-assessment, and clinical photographs were evaluated at 2, 4, 8, and 12 weeks post-treatment. Adverse events were also recorded to determine treatment safety. At 12 weeks post-treatment, mDPASI decreased 38.86%, from 0.929 ± 0.617 to 0.568 ± 0.415 (p < 0.05). The mean melanin index decreased 12.75%, from 208.650 ± 26.319 to 182.052 ± 17.028 (p < 0.05). In addition, the mean brightness score evaluated by two experts was 1.4, indicating 25-50% improvement. At the end of the study, 50% of the patients reported 50-75% improvement. Side effects included pain, mild edema, and bruising, which resolved spontaneously within 3 days. No serious side effects were found. Our results suggest that intradermal PRP therapy may be a safe and effective alternative for the treatment of Hori's nevus and can complement conventional interventions. However, further research with a larger sample size, control groups, and longer follow-up is needed to confirm these findings.

Preliminary nerve block for intradermal facial skin booster injections.

Preliminary nerve block for intradermal facial skin booster injections.

Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

BackgroundOptimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.MethodsParticipants aged 11–17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13–42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively.ResultsSpike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions.ConclusionThis is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.Graphical abstract

4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway.

Chronic prostatitis demonstrates a prevalence rate of nearly 5%-10% among young and middle-aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti-inflammatory properties of itaconic acid (IA) and its derivative, 4-Octyl itaconate (4-OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti-inflammatory effects in chronic prostatitis requires extensive research and validation. Human prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune-responsive gene 1 (IRG-1) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4-OI, while the control group received injections of saline. Western blot (WB), H&E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme-linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups. IHC analysis of human prostate tissue depicts that IRG-1 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4-OI increased Nrf2/HO-1 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1 h before intraperitoneal injection of 50 mg/kg 4-OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL-1β, IL-6, and TNF-α), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti-inflammatory effects of 4-OI in EAP. The present study indicates that 4-OI can alleviates EAP by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway, which may facilitate a novel approach toward prostatitis treatment.

Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review.

Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers. A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates. Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration. MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.

Complete Freund’s adjuvant-induced arthritis in rats: Anti-inflammatory and antioxidant properties of Allanblackia gabonensis (guttiferae) aqueous extract

Objectives: Allanblackia gabonensis (Guttiferae) stem bark extract is generally used in Cameroonian traditional medicine for its beneficial activities as antibiotics, anti-inflammatory, and antinociceptive. However, the claimed chronic anti-inflammatory and antioxidant effects have not yet been largely elucidated scientifically. The present study was designed to evaluate the anti-inflammatory and antioxidant effects of A. gabonensis stem bark aqueous extract on Freund’s complete adjuvant (CFA)-induced arthritis in rats. Materials and Methods: Arthritis was induced by intradermal injection of CFA (0.1 mL) into the right hind paw of each rat. Pain relieving effects were measured in the treated animals using an analgesiometer and antioxidant activity determined by measuring oxidative stress parameters. In addition, the hematological index, serum nitric oxide (NO), and transaminase activities were evaluated in the experimental animals. Results: A. gabonensis significantly protected animals against pain from day 15 to 18 and decreased (P &lt; 0.01) the paw edema from day 12 to the end of the experimentation (day 22). The number of white blood cells increased while the NO levels in serum and organs decreased in CFA animals as compared to the control group. An increase in serum transaminases was observed in the CFA group. A. gabonensis at the dose of 200 mg/kg significantly increased (36.36%) glutathione levels in the spleen in comparison with the CFA group. There was also a significant increase (P &lt; 0.01) of liver and cardiac catalase in animals receiving extract at 100 and 200 mg/kg. Conclusion: Our findings revealed the anti-arthritic and antioxidant potential of A. gabonensis and, thus, validate its traditional claim.

Delayed postoperative reactions to metamizole: a diagnostic challenge.

Background. Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed drug hypersensitivity reactions. Due to its favorable pharmacokinetic characteristics, metamizole is widely used in the postoperative period for pain control. Methods. Retrospective study of patients referred for allergological study between January 2012 and June2022 for postoperative hypersensitivity reactions. Clinical and diagnostic data were collected through review of patients' medical records. Twenty patients with postoperative hypersensitivity reactions were referred, of which 10 presented delayed reactions. We analyzed the results of skin prick, intradermal and patch tests performed with an intravenous metamizole solution as well as provocation tests performed with metamizole and acetylsalicylic acid. Cross-reactivity to non-steroidal anti-inflammatory drugs was excluded by confirmation of clinical tolerance to non-steroidal anti-inflammatory drugs or by acetylsalicylic acid provocation test. Results. In 7 of the 10 patients a delayed reaction to metamizole was diagnosed. These reactions were characterized as maculopapular exanthema, occurring in multiple postoperative settings. Skin tests were negative, except in one patient with late mild erythema in the ipsilateral upper limb and no reaction at the site of intradermal injection. Delayed hypersensitivity was demonstrated by late positive metamizole provocation tests. Conclusions. This study demonstrated that for a correct diagnosis a high degree of suspicion about possible delayed hypersensitivity drug reactions to metamizole in the postoperative setting is needed. In the investigation, provocation test with metamizole was decisive for diagnostic confirmation.

Retrospective Analysis of the Clinical Characteristics of Patients with Breast Cancer Treated with Telomerase Peptide Immunotherapy Combined with Cytotoxic Chemotherapy.

Telomerase activation, a critical step in cancer progression, occurs in approximately 95% of breast cancer cases. Telomerase is an attractive therapeutic target for breast cancer owing to its unique expression pattern. GV1001, a telomerase-derived peptide, is loaded onto human leukocyte antigen (HLA) class II antigen-presenting cells and binds to CD4+ T cell activating immune responses. This study aimed to evaluate the effectiveness and safety of co-administration of GV1001 and cytotoxic chemotherapy in patients with heavily-treated metastatic breast cancer. We analyzed 63 patients with breast cancer who received both GV1001 and cytotoxic chemotherapy. The GV 1001 administration methods involves 0.56 mg intradermal injection three times during the first week, one time at weeks 2, 3, 4, and 6, and then once every 28 days. The primary endpoint of this study was quality of life according to EORTC QLO-C30 and EQ-5D, while the secondary endpoint was the antitumor response according to RECIST 1.1, progression-free survival, overall survival, and toxicity profile. In 34 patients with HR+ breast cancer evaluable for tumor response, the disease control rate (DCR) and overall response rate (ORR) were 58.8% and 26.4%, respectively. The DCR and ORR were 66.6% and 28.5% in 21 patients with HER-2+ and 50% and 25% in patients with triple-negative breast cancer (TNBC), respectively. The median progression free survival was 10.4, 8.7, and 5.6 months in HR+, HER-2+, TNBC, respectively. The overall survival was 19.7, 13.2, and 9.4 months for patients with HR+, HER-2+, and TNBC, respectively. Most patients had an improved quality of life with statistically significant differences in some variables. The patients in this study experienced no additional toxicities other than the cytotoxic chemotherapy-associated side effects. GV1001 is a relatively safe anticancer vaccine for patients with heavily-treated breast cancer and can to improve the quality of life.

Evaluation of parenteral injection skills of medical undergraduates on mannequins in a tertiary care teaching hospital in South India – A cross-sectional study

Abstract Appropriate knowledge and expertise of parenteral injection is vital in the medical field. Hence we impart training on mannequins before the students practice on patients. This study was conducted to evaluate the skill exhibited by the students in parenteral injection skills, namely intravenous, intramuscular, intradermal and subcutaneous injections. The students were assessed for step based on the pre-validated check list created for Objective Structured Practical Examination. In this study, 16 % of the students failed to check the prescription order before starting the procedure. The name and the expiry date of the drug was not checked by 22 % of the students. Hundred percent of the students sterilized their hands. Loading of drug was done properly by 80 % of the students and 88 % of the students checked for air bubbles in the syringe and removed them properly. The site for injection was not sterilized by 26 percent of the students. Tourniquet was not applied by 19 percent of the students and 28 % of the students did not hold the bevel up during insertion for intravenous route. The steps where frequent faltering happened needs to be emphasized for them to perform better in a more efficient manner during the summative assessment as well as for future practice.

Immediate Lymphatic Reconstruction Using a Handheld Fluorescence Imaging Device.

Immediate lymphatic reconstruction (ILR) has traditionally required a fluorescent-capable microscope to identify lymphatic channels used to create a lymphaticovenous bypass (LVB). Herein, a new alternative method is described, identifying lymphatic channels using a commercially available handheld fluorescence imaging device. This was a single-center study of consecutive patients who underwent ILR over a 1-year period at a tertiary medical center. Intradermal injection of fluorescent indocyanine green dye was performed intraoperatively after axillary or inguinal lymphadenectomy. A handheld fluorescent imaging device (SPY-PHI, Stryker) rather than a fluorescent-capable microscope was used to identify transected lymphatic channels. Data regarding preoperative, intraoperative, and outcome variables were collected and analyzed. The handheld fluorescent imaging device was successfully able to identify transected lymphatic channels in all cases (n = 15). A nonfluorescent-capable microscope was used to construct the LVB in 14 cases. Loupes were used in one case. In 13 cases, ILR was unilateral. In two cases, bilateral ILR was performed in the lower extremities. All upper extremity cases were secondary to breast cancer (n = 7). Lower extremity cases (n = 8) included extramammary Paget disease of the penis, ovarian cancer, vulvar squamous cell carcinoma, squamous cell carcinoma of unknown origin, soft tissue sarcomas, cutaneous melanoma, and porocarcinoma. ILR, using indocyanine green injection with a handheld fluorescent imaging device, is both safe and effective. This method for intraoperative identification of lymphatic channels was successful, and LVB creation was completed in all cases. This approach makes ILR feasible when a fluorescent-capable microscope is unavailable, broadening access to more patients.

Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.

A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development. In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture. Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males. The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process. NCT01868464 (ClinicalTrials.gov).

Fractional CO 2 Laser Combined With Autologous Nanofat Injection Versus Fractional CO 2 Laser Combined With Platelet-Rich Plasma in the Treatment of Atrophic Acne Scars: A Split-Face Comparative Study With Optical Skin Imaging.

Atrophic acne scarring is a common problem. If left untreated, its implications can impair the quality of life. Various treatments, with differing degrees of success, are used to alleviate atrophic scars. To assess the efficacy of nanofat versus platelet-rich plasma (PRP) as an adjuvant therapy to fractional CO 2 laser (FCL) for atrophic acne scars. This study included 35 patients with atrophic acne scars who received 3 sessions of FCL at 1-month intervals on both sides of the face, followed by intradermal PRP injection on the left side. A single session of nanofat was injected into the right side of the face 2 weeks before the laser sessions. The evaluation was conducted 3 months after the final treatment session. After treatment, the right side of the face showed a significant reduction in Goodman scores and the indentation index of the Antera camera. The left side showed a significant difference in Goodman scores, yet the Antera camera showed a nonsignificant improvement. Nonetheless, the difference between the 2 sides was statistically insignificant. Atrophic acne scars improved with both modalities. As a result, cotreatment with these techniques may synergistically affect atrophic acne scars in efficacy and safety.

Intradermal Vaccination with Vididencel in MRD+ AML-Patients Leads to Increase in Antigen Presenting Cells and T-Cells to the Injection Site, Visualized Using Imaging Mass Cytometry, Showing Local Immune Cell Interactions Leading to Systemic Immune Responses

Background. Vididencel is an allogeneic leukemia-derived dendritic cell vaccine being developed as maintenance treatment in AML patients. Intradermal vaccination using vididencel is known to induce a local skin reaction, with local antigen processing by skin dendritic cells and direct presentation to T cells as well as dendritic cells, crawling out of the skin and presentation of the antigen in the draining lymph nodes for a full-blown immune response. It was previously shown that vididencel is able to induce an influx of immune cells in the skin using standard immunohistochemistry (van de Loosdrecht, 2018). In a phase 2 study vididencel was investigated as AML maintenance treatment after induction of CR1 with chemotherapy (ADVANCE-II, Clintrials.gov: NCT03697707). Using imaging mass cytometry up to 43 markers can be assessed in the same tissue section, to allow in depth analysis of the immune cells on a single cell level infiltrating in the dermis at the injection site. Methods. AML patients, in first complete remission with measurable residual disease (MRD +) and not planned for HSCT at inclusion, received 4 biweekly doses of vididencel followed by 2 booster doses at week 14 and 18. Skin biopsies of the injection site were taken 2 days after the 1 st, 4 th and 6 th vaccination. Control samples were collected from unvaccinated/unaffected skin in two patients and from healthy controls. Samples were fixed and embedded in paraffin, and stained by standard immunohistochemistry for immune cell markers like CD4, CD8 and CD68 in the central lab. For patients treated at Haukeland University Hospital (N=6), tissue sections were prepared, mounted and stained with the panel of 29 antibodies labelled with heavy metal isotopes for use in the Hyperion mass cytometry imaging. For each sample a region of interest (ROI) of 2.8mm 2 was scanned based on the localization of the immune infiltrates, guided by standard H&amp;E staining from neighboring slides. Results In 88.5% of patients injection site reactions were reported in this phase 2 study, characterized by redness, swelling and warmth at the site of intradermal injection, which were mild (maximum grade 1 or 2), and were of short duration (generally resolved within 12 days). Skin biopsies of a subset of 6 patients were analyzed using Hyperion. In standard single stain immunohistochemistry a large influx of CD4, CD8 and CD68 cells was observed in contrast to normal skin. Imaging mass cytometry confirmed these dense immune infiltrations. Using additional markers to characterize monocytes, dendritic cells and T-cells revealed that these cells are in close proximity and suggestive for cell-to-cell interaction (Figure 1). At sites of dense immune infiltration, influx of GranzymeB expressing CD8 T-cells and CD38 positive CD4 T-cells were observed as well as CD1c+ or CD141+ dendritic cells with high HLA-DR expression. These T-cells and dendritic cells are in close contact suggestive for patients' dendritic cells migrating from blood to skin, inducing a local immune response. Conclusion/discussion. Vaccination with vididencel triggered an inflammatory skin reaction in the majority of patients, with redness, warmth and swelling, of short duration, indicative for an active immune response at the site of injection. Skin biopsies using standard immunohistochemistry showed influx of activated CD4 and CD8 T cells as well as antigen presenting cell, including dendritic cells.Extended analysis with multiparameter imaging mass cytometry showed specific immune cell subsets infiltrating in these site of injection sites. The observed co-localization of the different immune subsets following vaccination supports the hypothesis of local antigen capturing by blood derived and local antigen presenting cells (Zuo et al, 2021). The local immune response may ultimately leads to a systemic immune response and disease control.

1629. Acceptability and Trust in the Low-dose Intradermal Mpox Vaccine: a Knowledge, Attitudes and Practices Sub-analysis of the Observational Study of Mpox Immunity (OSMI) in NYC

Abstract Background In the 2022 Mpox outbreak, the US FDA issued an EUA for a low-dose intradermal (ID) vaccination regimen to increase vaccine supply by five-fold. The ID regimen had yet to be evaluated for immunogenicity or tolerability in persons with HIV or for general acceptability. Methods We conducted a Knowledge, Attitudes and Practices survey to evaluate ID Mpox vaccine acceptability, comparing responses between participants with and without HIV and by route received. Results Of 119 ethnically and racially diverse respondents, 83% identified as male, 91% as LGBTQ+, median age was 38 years. 26% had HIV. 21% received ID/ID, 57% mixed subcutaneous (SC)/ID or ID/SC, and 18% SC/SC regimens. Vaccination route was similarly distributed across age, race, ethnicity, educational status, household income and HIV status. Knowledge of Mpox vaccines was moderate, with a mean of 4.36 of 7 responses correct. 62% were satisfied with Mpox vaccine rollout and 20% were neutral. 77% agreed that they trusted information received about the Mpox ID route by healthcare providers. Respondents with HIV were less likely to fully support the policy change to the ID route to stretch vaccine supply (Mann-Whitney p=0.039), but otherwise there were no significant differences between respondents with and without HIV in satisfaction with Mpox vaccine rollout, trust in vaccine-related information, confidence about ID regimen’s safety, efficacy, concern about cosmetic side effects, or overall acceptability. There were no significant differences between respondents by vaccination regimen in satisfaction with vaccine rollout, approval of the change toward ID formulation, concern about cosmetic side effects or overall acceptability. Compared to those who received mixed or ID/ID dosing regimens, SC/SC participants exhibited less confidence in efficacy of the ID formulation (Kruskal-Wallis p=0.015) and lower trust in information received by the US government about the ID formulation (p=0.01). Overall, 88% scored their Mpox vaccination experience as “excellent or very good,” and there was no difference between groups. Conclusion Survey responses from this clinical study sample suggest high acceptability of the ID regimen for Mpox vaccination in all groups, including among people with HIV and those who had received this regimen. Disclosures Ellie Carmody, MD, MPH, AstraZeneca: Stocks/Bonds|Merck: Stocks/Bonds Lalitha Parameswaran, MD, Pfizer: Grant/Research Support Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support

1495. Mpox Vaccine Immunity in People Living with HIV (PLWH) During The 2022 Mpox Outbreak in New York City

Abstract Background The WHO estimated that in 2022 49% of people affected by Mpox were PLWH. Due to initial vaccine shortage in 2022, a 1/5 dose of vaccine given intradermally (ID) was FDA-authorized (8/9/22). The ID regimen had never been evaluated in PLWH. Here we describe the characteristics, and IgG responses of Mpox vaccination in PLWH and HIV-negative participants. Methods We are conducting a longitudinal, observational study of adults with and without HIV who received the JYNNEOS vaccine or had Mpox infection in NYC. Clinical, demographic information, and Mpox H3L-specific serum IgG titers are assessed. Results 145 participants are enrolled: 25% are PLWH (median CD4 685 cells/mm3), 14% had Mpox disease and 21% had prior smallpox vaccination. 71% with Mpox disease were PLWH. The cohort is racially/ethnically diverse, mostly men (81%) and LGBTQ+ (90%). A third of the participants were recruited from NYC DOHMH pop-up vaccination site (34%), followed by peer or professional referral (20% &amp; 19%). Routes of vaccination were: SC-ID (49%), ID-ID (21%), SC-SC (20%), and ID-SC (10%). Redness (37%) &amp; swelling (21%) at site of injection were common reactions. Prior smallpox vaccination was associated with higher and sustained IgG titers even after one vaccine dose. Excluding such participants, antibody titers start declining post-dose 2 (antibody half-life of 103 days). There was no difference in IgG titers at 3 months post-dose 2 between PLWH and HIV-negative for ID or any other route. Titers at 3 months post-dose 2 in PLWH correlated with CD4 counts. Longer interval between the two doses contributed to higher titers. Mpox infection yielded to significantly higher titers than vaccination post-dose 1, but no after 2 doses. Conclusion Our study highlights the disproportionate burden of Mpox infection on PLWH. A diverse population representative of those most affected by 2022 Mpox was recruited. The vaccine, whether ID or SC, was well tolerated in PLWH and HIV-negative. More than two-thirds of participants with Mpox disease were PLWH. Individuals with prior smallpox vaccination maintain strong antibody levels post-dose 2, however, levels decline in individuals with no anterior prime. Our preliminary results show no negative impact of the ID dose regimen on antibody levels in PLWH. Disclosures Ellie Carmody, MD, MPH, AstraZeneca: Stocks/Bonds|Merck: Stocks/Bonds Lalitha Parameswaran, MD, MPH, Pfizer: Grant/Research Support Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support

Intradermal Sterile Water Injection: Safe and Effective Alternative for Relief of Acute Renal Colic in the Emergency Department

BackgroundThe optimal pain relief method for acute renal colic in the emergency department remains controversial. ObjectiveWe compared the safety and efficacy of intradermal sterile water injection (ISWI) to treatment with intramuscular (IM) diclofenac, intravenous (IV) opioids, and IV paracetamol in patients with acute renal colic. MethodsThis randomized, single-blind study included 320 patients with renal colic to one of four treatment groups. The first group received ISWI at four different points around the most painful flank area. Patients in the DI, PARA, and TRAM groups received 75 mg IM diclofenac, 1 g IV paracetamol, and 100 mg IV tramadol, respectively. Pain intensity was measured using a visual analog scale (VAS) before treatment and 15, 30, and 60 min after treatment. ResultsVAS scores 15 and 30 min after treatment were significantly lower in group ISWI than in groups DI, PARA, and TRAM. However, there were no significant differences in the decrease in the pain score at baseline and at 60 min after treatment. In addition, fewer patients required rescue analgesia in group ISWI than in group TRAM. However, no significant differences were observed between group ISWI and group DI or PARA in terms of the need for rescue analgesia. Finally, there were significantly fewer adverse events in group ISWI than in groups DI and TRAM. ConclusionsISWI had similar efficacy, faster pain relief, and lower need for rescue analgesia compared with diclofenac, paracetamol, and tramadol for the management of acute renal colic. In addition, ISWI was well-tolerated and had no adverse effects.

Delineation of DNA and mRNA COVID-19 vaccine-induced immune responses in preclinical animal models

ABSTRACT Nucleic acid vaccines are designed based on genetic sequences (DNA or mRNA) of a target antigen to be expressed in vivo to drive a host immune response. In response to the COVID-19 pandemic, mRNA and DNA vaccines based on the SARS-CoV-2 Spike antigen were developed. Surprisingly, head-to-head characterizations of the immune responses elicited by each vaccine type has not been performed to date. Here, we have employed a range of preclinical animal models including the hamster, guinea pig, rabbit, and mouse to compare and delineate the immune response raised by DNA, administered intradermally (ID) with electroporation (EP) and mRNA vaccines (BNT162b2 or mRNA-1273), administered intramuscularly (IM), expressing the SARS-CoV-2 WT spike antigen. The results revealed clear differences in the quality and magnitude of the immune response between the two vaccine platforms. The DNA vaccine immune response was characterized by strong T cell responses, while the mRNA vaccine elicited robust humoral responses. The results may assist in guiding the disease target each vaccine type may be best matched against and suggest mechanisms to further enhance the breadth of each platform’s immune response.