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• Ability to delivery insulin via skin with accurate dosing using multi-layer detachable microneedles. • Ability to target drugs only in the dermis using multi-layer detachable microneedles. • Ability to sustain the release of insulin into blood circulation through the use of detachable microneedles. • Ability to stabilize insulin at room temperature. • Explaination at the mechanistic level of insulin stabilization. The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration. [Display omitted] [ABSTRACT FROM AUTHOR]

Monitoring personal ultraviolet (UV) exposure facilitates risk mitigation against UV‐induced skin aging and skin cancer, the most common malignancy in North America, Europe, and Australia. UV radiometers convey real‐time information on local UV irradiance, while UV dosimeters count accumulated UV exposure over time. These devices can help users manage exposure levels in order to reach a healthy daily dose of UV light required for vitamin D production without exceeding erythemal limits that would increase skin cancer risk. However, personal UV detectors still suffer from several limitations. Wearable electronic UV sensors are relatively bulky, heavy, and expensive, while the more commonly used on‐skin disposable colorimetric UV sensors suffer from short service life, skin discomfort, and high accumulated costs when used daily as recommended. Intradermal colorimetric UV nanosensors can overcome these limitations, offering long‐term, comfortable, and inexpensive naked‐eye colorimetric indication of intradermal UV irradiance. Now, a new generation of UV‐sensing intradermal pigments with an improved design offers better tunability, stability, and biocompatibility. These UV‐photochromic nanosensors may be operated as UV dosimeters or simple sunscreen efficacy monitors, depending on the formulation, and can remain functional and re‐usable in the dermis for years. [ABSTRACT FROM AUTHOR]

• Immunogenicity data for single versus 2-dose JYNNEOS regimens were previously limited. • We evaluate OPXV-specific serologic responses in individuals without rash presenting for JYNNEOS mpox vaccination. • IgG antibody responses increased during the 41 days post vaccination followed by a decline by 180 days but continued to remain IgG seropositive. • Serologic response did not vary by age, sex, or HIV status, but did vary by vaccine administration route. We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at ∼28, ∼42–56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants' IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42–56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. COVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of intradermal (ID) and intramuscular (IM) vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV)-modified live vaccine (MLV) in piglets on serum copeptin levels and hematological profile. This study included 104 suckling piglets (2 weeks of age) from a commercial farrow-to-finish pig farm suffering from positive unstable PRRSV status. Animals were assigned to four groups, with two replicates (13 piglets/group/replicate); group A: IM vaccination with a PRRSV MLV vaccine, group B: ID vaccination with the same vaccine, group C: ID of Diluvac Forte, and group D: IM of Diluvac Forte. Blood samples were collected from the same three pigs/group/replicate at 4, 7, and 10 weeks of age. Blood samples were used for the performance of the complete blood count, and they were also examined by PCR for PRRSV and by ELISA for copeptin. No significant differences in serum copeptin levels and the number of blood cell counts (packed cell volume—PCV, numbers of white blood cells—WBCs, and platelets number—PLTs) were noticed in the same group over time and among groups. In conclusion, it seems that the vaccination against PRRSV does not affect the levels of the released copeptin. Based on our results, the measurement of serum copeptin could not be proposed as a potential stress biomarker in pigs.

Simple Summary: The objective of this study was to investigate the impact of intradermal (ID) versus intramuscular (IM) vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV)-modified live vaccine (MLV) in piglets on serum copeptin and hematological profile. The study included 104 suckling piglets (2 weeks of age) from a commercial farrow-to-finish PRRSV-positive pig farm. Blood samples were collected from piglets at 4, 7, and 10 weeks of age. Blood samples were used for the performance of the complete blood count and examination by PCR for PRRSV and by ELISA for copeptin. No significant differences in serum copeptin levels and the number of blood cell counts were noticed in the same group over time and among groups. In conclusion, it seems that the PRRSV vaccination does not affect the levels of the released copeptin. This study aimed to investigate the impact of intradermal (ID) and intramuscular (IM) vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV)-modified live vaccine (MLV) in piglets on serum copeptin levels and hematological profile. This study included 104 suckling piglets (2 weeks of age) from a commercial farrow-to-finish pig farm suffering from positive unstable PRRSV status. Animals were assigned to four groups, with two replicates (13 piglets/group/replicate); group A: IM vaccination with a PRRSV MLV vaccine, group B: ID vaccination with the same vaccine, group C: ID of Diluvac Forte, and group D: IM of Diluvac Forte. Blood samples were collected from the same three pigs/group/replicate at 4, 7, and 10 weeks of age. Blood samples were used for the performance of the complete blood count, and they were also examined by PCR for PRRSV and by ELISA for copeptin. No significant differences in serum copeptin levels and the number of blood cell counts (packed cell volume—PCV, numbers of white blood cells—WBCs, and platelets number—PLTs) were noticed in the same group over time and among groups. In conclusion, it seems that the vaccination against PRRSV does not affect the levels of the released copeptin. Based on our results, the measurement of serum copeptin could not be proposed as a potential stress biomarker in pigs. [ABSTRACT FROM AUTHOR]

Purpose: Botulinum toxin has played a remarkable role in management of forehead wrinkles. Most used is intramuscular technique due to its deposition into the muscles, however, with adverse effects like brow ptosis. This study has been designed for the evaluation of efficacy for intradermal v/s intramuscular route of botulinum toxin injections for forehead wrinkles using clinical correlation. Methods: This study included a clinical trial of 32 facial halves divided equally into intradermal and intramuscular injection technique groups, receiving total dose of 8 U. Results were assessed by clinical examination upto 2 weeks and 4 weeks with parameters; objective wrinkle rate, eyebrow height, eyebrow movement, pain, and satisfaction after treatment. Result: Results showed least mean for objective wrinkle rate in intramuscular group, showing statistically significant improvement. Overall improvement in eyebrow height and eyebrow movement were slightly more for intramuscular group. Pain was lesser for intradermal group, whereas satisfaction of patient of patient post treatment is similar for both the groups. Conclusion: Among intradermal and intramuscular botulinum toxin injection technique, the effect and potency were better for intramuscular technique, whereas the patient comfort and compliance were better for intradermal technique. [ABSTRACT FROM AUTHOR]

The lymphatic system is active in several processes that regulate human diseases, among which cancer progression stands out. Thus, various drug delivery systems have been investigated to promote lymphatic drug targeting for cancer therapy; mainly, nanosized particles in the 10–150 nm range quickly achieve lymphatic vessels after an interstitial administration. Herein, a strategy to boost the lymphotropic delivery of Rose Bengal (RB), a hydrosoluble chemotherapeutic, is proposed, and it is based on the loading into Transfersomes (RBTF) and their intradermal deposition in vivo by microneedles. RBTF of 96.27 ± 13.96 nm (PDI = 0.29 ± 0.02) were prepared by a green reverse-phase evaporation technique, and they showed an RB encapsulation efficiency of 98.54 ± 0.09%. In vitro , RBTF remained physically stable under physiological conditions and avoided the release of RB. In vivo , intravenous injection of RBTF prolonged RB half-life of 50 min in healthy rats compared to RB intravenous injection; the RB half-life in rat body was further increased after intradermal injection reaching 24 h, regardless of the formulation used. Regarding lymphatic targeting, RBTF administered intravenously provided an RB accumulation in the lymph nodes of 12.3 ± 0.14 ng/mL after 2 h, whereas no RB accumulation was observed after RB intravenous injection. Intradermally administered RBTF resulted in the highest RB amount detected in lymph nodes after 2 h from the injection (84.2 ± 25.10 ng/mL), which was even visible to the naked eye based on the pink colouration of the drug. In the case of intradermally administered RB, RB in lymph node was detected only at 24 h (13.3 ± 1.41 ng/mL). In conclusion, RBTF proved an efficient carrier for RB delivery, enhancing its pharmacokinetics and promoting lymph-targeted delivery. Thus, RBTF represents a promising nanomedicine product for potentially facing the medical need for novel strategies for cancer therapy. [Display omitted] • RBTF are physically stable in physiological states and prevent premature RB release. • RBTF increase RB half-life from 30 to 90 min when intravenously injected. • RB half-life increases up to 24 h after intradermal injection of RBTF and RB solution. • RBTF highly potentiate RB lymph-node accumulation when intradermally deposited. • RBTF circulation in the lymphatics encourages their evaluation for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Exosomes have gained attention for their potential in skin rejuvenation. Currently, most exosome products are available for topical administration, and the use of subdermal injection as a route of administration has not been approved. Aims: The purpose of this case report is to describe a case of skin necrosis that occurred following an intradermal injection of lyophilized exosomes. Materials and Methods: We hereby report a case of a middle‐aged man who experienced adverse effects after receiving an intradermal injection of lyophilized exosomes. Multiple injections of an exosome product were administered to treat enlarged facial pores. Shortly after the injection, the patient felt pain and noticed several dark red bumps. Three days after injection, the lesions transformed into palpable, painful, non‐blanchable purplish papules and nodules, accompanied by central, tiny crusted erosions. The residual product was injected into the upper arm using an intradermal method. Similar lesions also appeared, and a skin biopsy showed necrotic keratinocytes, leukocytoclastic vasculitis, and eccrine necrosis. Results: There are few reports available regarding complications, especially those related to intradermal exosomes. These complications include multiple foreign‐body granulomatous reactions at the injection sites. In our case, oral prednisolone was administered for a duration of 7 days. After the treatment, the lesions exhibited notable improvement, eventually leaving post‐inflammatory hyperpigmentation. Conclusion: Utilizing exosomes through unapproved methods should be avoided due to the possibility of adverse reactions that could cause aesthetic issues. [ABSTRACT FROM AUTHOR]

Background: Optimising 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. Methods: Participants 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. Results: Spike 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. Conclusion: This 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. [ABSTRACT FROM AUTHOR]

Syringocystadenoma papilliferum (SCAP) is a benign adnexal tumor commonly found on the scalp and face, and often associated with nevus sebaceous, with about half of cases appearing in early childhood. SCAP exhibits cystic invaginations with papillary structures and a double-layered glandular epithelium linked to the epidermal surface and stromal plasma cells. We are reporting a rare instance of intradermal SCAP in a 55-year-old male. He sought evaluation for a long-standing asymptomatic dark-pink papule in his left popliteal fossa, measuring 0.7 x 0.5 x 0.4 cm. A shave biopsy revealed papillary dermal fibrosis, glandular epithelium with apocrine secretion, and papillary projections without an epidermal connection. Infundibulofollicular keratinization was observed, along with stromal plasma cells. The patient chose local excision as the treatment option. This case highlights the rarity of intradermal SCAP, especially in the left popliteal fossa, with only one other reported case in the literature. [ABSTRACT FROM AUTHOR]

Introduction: Rabies is a zoonotic disease that can be fatal and continues to impose a significant financial burden on developing countries. Recently, there have been advancements in the introduction of cell culture vaccines and immunoglobulin, as well as the approval of Intradermal (ID) schedules for vaccine administration. Aim: To assess the knowledge of doctors in Rewa District regarding the National Guidelines for Rabies Prophylaxis in 2019. Materials and Methods: A cross-sectional study was conducted, involving doctors from tertiary healthcare centres, district hospitals, and private practices. Data were collected over a period of one month from 206 doctors using a Google form, which included information about their field of practice and their knowledge of recent guidelines on Rabies prophylaxis. Data analysis was performed using the Chi-square test. Results: Out of the 206 doctors surveyed, 92 (44.7%) were male. A 56.7% of the doctors were aware of the regimen and dosage for ID administration of the Anti Rabies Vaccine, (ARV) and 44.6% were knowledgeable about the modification of Post-Exposure Prophylaxis (PEP) to Pre-Exposure Prophylaxis (PrEP) in the Essen regimen. Furthermore, 70.9% of the doctors were familiar with the dosage of Human Rabies Immunoglobulin (HRIG), while 42.7% knew how to manage animal bites in immunocompromised patients. Conclusion: The study revealed a lack of sufficient knowledge on various aspects of rabies management among the doctors surveyed. This underscores the need for reorientation programs and Continuing Medical Education (CMEs) training to be provided to doctors to enhance their knowledge of rabies and improve the effective management of animal bites.

Introduction: Rabies is a zoonotic disease that can be fatal and continues to impose a significant financial burden on developing countries. Recently, there have been advancements in the introduction of cell culture vaccines and immunoglobulin, as well as the approval of Intradermal (ID) schedules for vaccine administration. Aim: To assess the knowledge of doctors in Rewa District regarding the National Guidelines for Rabies Prophylaxis in 2019. Materials and Methods: A cross-sectional study was conducted, involving doctors from tertiary healthcare centres, district hospitals, and private practices. Data were collected over a period of one month from 206 doctors using a Google form, which included information about their field of practice and their knowledge of recent guidelines on Rabies prophylaxis. Data analysis was performed using the Chi-square test. Results: Out of the 206 doctors surveyed, 92 (44.7%) were male. A 56.7% of the doctors were aware of the regimen and dosage for ID administration of the Anti Rabies Vaccine, (ARV) and 44.6% were knowledgeable about the modification of Post-Exposure Prophylaxis (PEP) to Pre-Exposure Prophylaxis (PrEP) in the Essen regimen. Furthermore, 70.9% of the doctors were familiar with the dosage of Human Rabies Immunoglobulin (HRIG), while 42.7% knew how to manage animal bites in immunocompromised patients. Conclusion: The study revealed a lack of sufficient knowledge on various aspects of rabies management among the doctors surveyed. This underscores the need for reorientation programs and Continuing Medical Education (CMEs) training to be provided to doctors to enhance their knowledge of rabies and improve the effective management of animal bites. [ABSTRACT FROM AUTHOR]

The administration of viral vector and mRNA vaccine booster effectively induces humoral and cellular immune responses. Effector T cell responses after fractional intradermal (ID) vaccination are comparable to those after intramuscular (IM) boosters. Here, we quantified T cell responses after booster vaccination. ChAdOx1 nCoV-19 vaccination induced higher numbers of S1-specific CD8+ memory T cells, consistent with the antibody responses. Effector memory T cell phenotypes elicited by mRNA vaccination showed a similar trend to those elicited by the viral vector vaccine booster. Three months post-vaccination, cytokine responses remained detectable, confirming effector T cell responses induced by both vaccines. The ID fractional dose of ChAdOx1 nCoV-19 elicited higher effector CD8+ T cell responses than IM vaccination. This study confirmed that an ID dose-reduction vaccination strategy effectively stimulates effector memory T cell responses. ID injection could be an improved approach for effective vaccination programs. [ABSTRACT FROM AUTHOR]

Background. Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). Methods. Three cohorts of healthy adult subjects were enrolled and given three doses of 25 μg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. Results. A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: −7.5–51.6%). In addition to reducing moderate–severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. Conclusions. This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study. [ABSTRACT FROM AUTHOR]

The genus Borrelia is represented by spirochetes that, once entered the human or animal body, can migrate to different organs, including the central nervous system. The aim of the study was to develop a murine neuroborreliosis model by inoculating a strain of Borrelia burgdorferi (Bb). 2 studies were conducted using BALB/c and CD1 mice strains, female, 8 weeks old, 22 grams at baseline. The selected animals were inoculated with Bb (106 spirochetes/mL), depending on the protocol, intradermally (100µL/animal) or intracerebrally (10µL/animal). For the evaluation of the neuroborreliosis development, endpoints were established at 1, 3, 6, 8 and 13 weeks post-infection, when samples of dura mater, brain, ear, heart, knee joint and bladder were collected, and maintained in culture medium specific for the growth of Borrelia. Recovery of Bb was possible from samples harvested 7 days post-infection from animals inoculated both intradermally and intracerebrally. Through the experiments we have developed a model of neuroborreliosis in two mice strains that can be useful for the study of the development of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background and Objective: Tranexamic acid (TXA) has recently shown promising results in the treatment of melasma. The objective of this study was to generate statistical evidence on the efficacy of TXA with different routes. Materials and Methods: We searched studies in PubMed, Cochrane, ClinicalTrials.gov, and Scopus using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A change in melasma area and severity index (MASI)/modified MASI score from the baseline at the end of 8 and 12 weeks was seen. Inverse variance method was used for continuous data to measure standard mean difference (SMD) at a 95% confidence interval (CI). RevMan version 5.4 was used for analysis, and statistical heterogeneity across studies was reported using I2 statistics. P < 0.05 was considered significant. Results: Totally, 28 randomized control trials were included. At 8 weeks, oral TXA showed a significant change in SMD of 1.61, 95% CI 0.44-2.79, P = 0.007; at 12 weeks, oral TXA showed SMD of 2.39, 95% CI 1.42-3.35, P < 0.00001 compared to adjuvant treatment. At 8 weeks, topical TXA did not show a significant change with SMD of - 0.05, 95% CI - 1.08-0.97, P = 0.92; at 12 weeks, topical TXA did not show a significant change with SMD of 0.66, 95% CI -0.10-1.42, P = 0.09 compared to adjuvant treatment. Similarly, for intradermal TXA at 8 weeks, results were not significant with SMD of 1.21, 95% CI -0.41-2.83, P = 0.14, and at 12 weeks, SMD was -0.55, 95% CI -2.27-1.18, P = 0.54 compared to adjuvant treatment. Conclusion: Tranexamic acid in an oral formulation can be used along with adjuvant treatment for the management of melasma. Data are still required for topical and intradermal routes. Owing to the fact that our included studies had a lot of heterogeneity, more research is needed along with addressing the adverse effects of tranexamic acid as well as its variation in different skin colors. [ABSTRACT FROM AUTHOR]

Introduction Atrophic scars are the most common and frequent complication of acne. The use of platelet-rich plasma (PRP) through the release of growth factors, cytokines and chemokines from a-granules may aid in the treatment of such atrophic scars. Objective To compare the effectiveness of intradermal administration of PRP with topical administration using micro-needling for treatment of atrophic acne scars. Methods Two subjects with atrophic scars were selected. Procedures were performed three times for the first subject and two times for the second subject with an interval of 3 weeks. The right side of the face was treated using intradermal PRP, while the left side was treated using micro-needling PRP. Assessments of clinical improvement were obtained by evaluating the photos of each treatment and assessment of the severity of the scar used the Global Acne Scarring Grading System and Lipper & Perez Score. Results Facial area treated using intradermal PRP in the first patient experienced an 85.71% improvement in Global Acne Scarring Grading System and 68.59% improvement in Lipper & Perez score after 9 weeks of treatment, while the second patient experienced 64.28% improvement in Global Acne Scarring Grading System and 71.35% improvement in Lipper & Perez score after 6 weeks of treatment. Furthermore, the first patient treated with micro-needling experienced 53.33% improvement in Global Acne Scarring Grading System along with 62.71% improvement in Lipper & Perez Score after 9 weeks of treatment. While the second patient experienced 61.90% improvement in Global Acne Scarring Grading System and 58.65% improvement in Lipper and Perez Score after 6 weeks of treatment. Conclusion Intradermal administration of PRP is more effective compared to topical administration using micro-needling, especially for boxcars and rolling scars. However, with notably more complications such as edema, pain, and longer downtime. [ABSTRACT FROM AUTHOR]

Shigellosis remains a global health concern, especially in low- and middle-income countries. Despite improvements in sanitation, the absence of a licensed vaccine for human use has prompted global health organizations to support the development of a safe and effective multivalent vaccine that is cost-effective and accessible for limited-resource regions. Outer Membrane Vesicles (OMVs) have emerged in recent years as an alternative to live attenuated or whole-inactivated vaccines due to their immunogenicity and self-adjuvating properties. Previous works have demonstrated the safety and protective capacity of OMVs against Shigella flexneri infection in mouse models when administered through mucosal or intradermal routes. However, some immunological properties, such as the cellular response or cross-protection among different Shigella strains, remained unexplored. In this study, we demonstrate that intradermal immunization of OMVs with needle-free devices recruits a high number of immune cells in the dermis, leading to a robust cellular response marked by antigen-specific cytokine release and activation of effector CD4 T cells. Additionally, functional antibodies are generated, neutralizing various Shigella serotypes, suggesting cross-protective capacity. These findings highlight the potential of OMVs as a promising vaccine platform against shigellosis and support intradermal administration as a simple and painless vaccination strategy to address this health challenge. [ABSTRACT FROM AUTHOR]

The development of cross-protective vaccines against the zoonotic swine influenza A virus (swIAV), a potential pandemic-causing agent, continues to be an urgent global health concern. Commercially available vaccines provide suboptimal cross-protection against circulating subtypes of swIAV, which can lead to worldwide economic losses and poor zoonosis deterrence. The limited efficacy of current swIAV vaccines demands innovative strategies for the development of next-generation vaccines. Considering that intramuscular injection is the standard route of vaccine administration in both human and veterinary medicine, the exploration of alternative strategies, such as intradermal vaccination, presents a promising avenue for vaccinology. This investigation demonstrates the first evaluation of a direct comparison between a commercially available multivalent swIAV vaccine and monovalent whole inactivated H1N2 swine influenza vaccine, delivered by intradermal, intranasal, and intramuscular routes. The monovalent vaccines were adjuvanted with NanoST, a cationic phytoglycogen-based nanoparticle that is combined with the STING agonist ADU-S100. Upon heterologous challenge, intradermal vaccination generated a stronger cross-reactive nasal and serum antibody response in pigs compared with intranasal and intramuscular vaccination. Antibodies induced by intradermal immunization also had higher avidity compared with the other routes of vaccination. Bone marrow from intradermally and intramuscularly immunized pigs had both IgG and IgA virus-specific antibody-secreting cells. These studies reveal that NanoST is a promising adjuvant system for the intradermal administration of STING-targeted influenza vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. Methods: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. Results. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Conclusion: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model. [ABSTRACT FROM AUTHOR]

Background: Melasma is a common dermatosis in both men and women showing varying degrees of success with treatment. Relapse of melasma is high in dark skin types, which necessitates the need for finding a modality of treatment, which not only treats but also prevents relapse. Aims: To study the effectiveness of platelet-rich plasma (PRP) in patients of melasma both clinically and dermoscopically in dark skin types. Materials and Methods: A prospective study of 20 female patients of Fitzpatrick skin type IV–V with mixed type of melasma and bilateral involvement of the face were enrolled for the study. PRP was injected intradermally at 4 weeks interval for three sittings, and the results were assessed clinically (by modified melasma area and severity score) and dermoscopically. Patients were counselled to ensure strict sun protection measures. Patient satisfaction was noted at baseline, 4 weeks, 8 weeks, and 12 weeks. Patients were followed up for 3 months to see for any relapse of the pigmentation. The follow-up showed no relapse of melasma in these patients. Statistical Analysis: Analysis of variance was used with Bonferroni correction for modified melasma area and severity score at various time interval. Subject global aesthetic improvement scale (SGAIS) and physician global esthetic improvement scale (PGAIS) were expressed in counts. P-value ≤ 0.05 was considered significant. Results: Modified melasma area and severity score and dermoscopic changes showed statistically significant improvement compared at the end of study in mild to severe cases. The subjective assessment was made by PGAIS. Patient satisfaction levels (assessed by SGAIS) also showed significant improvement in successive weeks of treatment. Few patients had mild redness and burning post procedure, which resolved spontaneously after few hours. Conclusion: From this study we concluded that PRP shows a significant improvement in melasma after 12 weeks of treatment with no relapse even after 3 months. Hence, PRP may be used not only as an adjuvant but also as a first line treatment in the view of longer sustained results when combined with strict sun protection. There is a paucity of studies showing results of PRP treatment in dark skin types, which is more resistant to treatment than lighter skin. Moreover, clinical improvement should not be the only parameter to decide on stopping treatment as chances of relapse can be higher. Dermoscopic evaluation helps in determining the changes in vasculature (telangiectasias) and pigmentation (dots and globules), which are better indicators of success of treatment. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust T H 1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines. [Display omitted] • The RALA Peptide can deliver multiple mRNA in a nanoformulation. • The RALA/SME vaccine can be delivered intradermally or intramuscularly. • The RALA/SME vaccine induces both an antibody and T-cell response. • The RALA/SME vaccine exhibits no toxicities following vaccination. • The RALA/SME vaccine produces neutralising antibodies against SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy. Methods Persons aged ≥65 years who were vaccinated with 2-dose ChAdOx1 12–24 weeks earlier were randomized to receive a booster vaccination by either ID (20 µg mRNA-1273 or 10 µg BNT162b2) or intramuscular (IM) (100 µg mRNA-1273 or 30 µg BNT162b2) route. Anti–receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibody (NAb), and interferon gamma (IFN-γ)–producing cells were measured at 2–4 weeks following vaccination. Results Of 210 participants enrolled, 70.5% were female and median age was 77.5 (interquartile range, 71–84) years. Following booster dose, both ID vaccinations induced 37% lower levels of anti-RBD IgG compared with IM vaccination of the same vaccine. NAb titers against ancestral and Omicron BA.1 were highest following IM mRNA-1273 (geometric mean, 1718 and 617), followed by ID mRNA-1273 (1212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN-γ responses were similar or higher in the ID groups compared with IM groups. ID route tended to have fewer systemic adverse events (AEs), although more local AEs were reported in the ID mRNA-1273 group. Conclusions Fractional ID vaccination induced lower humoral but comparable cellular immunity compared to IM and may be an alternative for older people. Clinical Trials Registration TCTR20220112002. [ABSTRACT FROM AUTHOR]

Botulinum toxin type A (BTA) is a neurotoxin used for both cosmetic and non-cosmetic purposes. BTA is commonly administered as an intramuscular injection to treat wrinkles. However, when it comes to treating forehead wrinkles, intramuscular injection is associated with a greater rate of ptosis. Intradermal injection is currently thought to be a better alternative. We searched PubMed and Google Scholar for research articles published between 1989 and 2023 using the following keywords: "intradermal," "intramuscular," "botulinum toxin," and "forehead wrinkle." The search yielded three randomized controlled trials and a double-blind, split-face case report on 58 patients. We found that although intradermal and intramuscular injections have symmetrical anti-wrinkle effects, the former results in a lower rate of ptosis and a greater degree of pain. [ABSTRACT FROM AUTHOR]

Summary: Background: This report details how one large medical center in the Metropolitan New York area re-purposed a drive-through COVID-19 vaccination structure to handle a surge in Mpox cases in July 2022.Methods/Results: Simultaneous to on-going COVID -19 vaccination and testing, Mpox vaccination was rolled out in the same drive through structure. More than 1,820 Jynneos (Smallpox and Monkeypox Vaccine, Live, Non-replicating) vaccine dosages were delivered subcutaneously and then intradermally to 1,123 individuals through the open window of their vehicles, averaging 8–10 patients an hour. Five vaccine recipients suffered Mpox rash; there was no exposure among healthcare providers. Conclusion: Drive-through vaccination is an efficient model to be redeployed for future unexpected vaccine initiatives.

An unconjugated composite peptide vaccine targeting multiple conserved influenza epitopes from hemagglutinin, neuraminidase, and matrix protein and formulated with a safe and highly potent adjuvant, Army Liposome formulation (ALFQ), generated broad and durable immune responses in outbred mice. The antibodies recognized specific epitopes in influenza peptides and several human, avian, and swine influenza viruses. Comparable antibody responses to influenza viruses were observed with intramuscular and intradermal routes of vaccine administration. The peptide vaccine induced cross-reactive antibodies that recognized influenza virus subtypes A/H1N1, A/H3N2, A/H5N1, B/Victoria, and B/Yamagata. In addition, immune sera neutralized seasonal and pandemic influenza strains (Group 1 and Group 2). This composite multi-epitope peptide vaccine, formulated with ALFQ and administered via intramuscular and intradermal routes, provides a high-performance supra-seasonal vaccine that would be cost-effective and easily scalable, thus moving us closer to a viable strategy for a universal influenza vaccine and pandemic preparedness. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is responsible for incapacitating joint pains and is a significant health hazard in many countries. Though a definite need for a CHIKV vaccine is felt, long disappearance of CHIKV from circulation in humans has been a concern for vaccine development. Use of two separate pattern recognition receptor ligands has been shown to enhance immune response to the administered antigen. In addition, intradermal delivery of vaccine tends to mimic the natural mode of CHIKV infection. Therefore, in this study, we explored whether intradermal and intramuscular immunization with inactivated CHIKV (I–CHIKV) supplemented with dual pattern-recognition receptor ligands, CL401, CL413, and CL429, is an effective approach to enhancing antibody response to CHIKV. Our in vivo data show that I–CHIKV supplemented with these chimeric PRR ligands induces enhanced neutralizing antibody response after intradermal delivery, but is less efficient after intramuscular immunization. These results suggest that intradermal delivery of I–CHIKV with chimeric adjuvants is a possible way to elicited a better antibody response. • Though a need is felt, long disappearance of CHIKV has been a concern for vaccine manufacture. • Type of antigen–adjuvant combination and delivery route are important to induce optimum antibody response. • I–CHIKV supplemented with the chimeric PRR ligands CL401, CL413, and CL429 induced a robust neutralizing antibody response. • Intradermal delivery of unadjuvanted or adjuvanted I–CHIKV elicited a higher antibody response than intramuscular delivery. [ABSTRACT FROM AUTHOR]

Background. Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). Methods. Three cohorts of healthy adult subjects were enrolled and given three doses of 25 μg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. Results. A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: −7.5–51.6%). In addition to reducing moderate–severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. Conclusions. This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study.

The administration of viral vector and mRNA vaccine booster effectively induces humoral and cellular immune responses. Effector T cell responses after fractional intradermal (ID) vaccination are comparable to those after intramuscular (IM) boosters. Here, we quantified T cell responses after booster vaccination. ChAdOx1 nCoV-19 vaccination induced higher numbers of S1-specific CD8+ memory T cells, consistent with the antibody responses. Effector memory T cell phenotypes elicited by mRNA vaccination showed a similar trend to those elicited by the viral vector vaccine booster. Three months post-vaccination, cytokine responses remained detectable, confirming effector T cell responses induced by both vaccines. The ID fractional dose of ChAdOx1 nCoV-19 elicited higher effector CD8+ T cell responses than IM vaccination. This study confirmed that an ID dose-reduction vaccination strategy effectively stimulates effector memory T cell responses. ID injection could be an improved approach for effective vaccination programs.

Botulinum toxin type A (BTA) is a neurotoxin used for both cosmetic and non-cosmetic purposes. BTA is commonly administered as an intramuscular injection to treat wrinkles. However, when it comes to treating forehead wrinkles, IM is associated with a greater rate of ptosis. Intradermal injection is currently thought to be a better alternative. We searched PubMed and Google Scholar for research articles published between 1989 and 2023 using the following keywords: “intradermal,” “intramuscular,” “botulinum toxin,” and “forehead wrinkle.” The search yielded three randomized controlled trials and a double-blind, split-face case report on 58 patients. We found that although intradermal and intramuscular injections have symmetrical anti-wrinkle effects, the former results in a lower rate of ptosis and a greater degree of pain.

Background External anogenital warts are considered the commonest viral sexually transmitted infection that has serious negative psychological effects. Various destructive modalities have been tried with variable results with high recurrence rates in contrast to intralesional immunotherapy. Aim to evaluate the efficacy, safety, and tolerability of intralesional Measles Mumps Rubella (MMR) vaccine versus intralesional and intradermal purified protein derivative (PPD) in treatment of female anogenital wart. Methods This randomized clinical trial included 69 female patients with anogenital warts above 18 years old divided into three equal groups. Group 1 received intralesional MMR at a dose of (0.2 ml) in the largest wart, group 2 received intralesional (IL)PPD (0.2 ml) in the largest wart, group 3 received intradermal(ID) PPD (0.2 ml) every 2 weeks till improvement or for a maximum five treatment sessions. The follow up period was 6 months after the last treatment session. Results Although it was not statistically significant, overall response was higher in the MMR group (78.3 %) versus IL PPD (69.6%) and ID PPD (56.5%). The highest cure rates were after the 4th session in the MMR group and the 5th session in both IL PPD and ID PPD groups with slightly lower numbers of sessions needed for cure in the MMR group (4 sessions) versus both PPD group (5 sessions). IL PPD group showed non statistically significant higher rates of complications in comparison with ID PPD and MMR group. IL PPD showed higher rates of recurrence than MMR and ID PPD groups during the follow up period without significant difference. There was significant difference between level of IL12 before and after treatment in every group. In addition, there was significant difference between level of IL12 after treatment between IL PPD and other both groups. Conclusion MMR, intralesional PPD and intradermal PPD are effective in female anogenital warts with higher safety profile of MMR. [ABSTRACT FROM AUTHOR]

Background: At the commencement of a pandemic, it is important to consider the impact of respiratory infections on the health system and the possibility of vaccine shortages due to increased demand. In the event of an influenza vaccine shortage, a strategy for administration of fractional influenza vaccine doses might be considered. This article reviews the available evidence for efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing, and summarizes the National Advisory Committee on Immunization (NACI) recommendations on fractional dosing strategies by public health programs in Canada. Methods: Two rapid literature reviews were undertaken to evaluate the efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing via the intramuscular or intradermal route. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. Results: There was limited evidence for the effectiveness of fractional influenza vaccine dosing. Fractional dosing studies were primarily conducted in healthy individuals, mainly young children and infants, with no underlying chronic conditions. There was fair evidence for immunogenicity and safety. Feasibility issues were identified with intradermal use in particular. Conclusion: NACI recommended that, in the event of a significant population-level shortage of influenza vaccine, a full-dose influenza vaccine should continue to be used, and existing vaccine supply should be prioritized for those considered to be at high risk or capable of transmitting to those at high risk of influenza-related complications or hospitalizations. NACI recommended against the use of fractional doses of influenza vaccine in any population. [ABSTRACT FROM AUTHOR]

The microbiome is an integral and dynamic component of the host and is emerging as a critical determinant of immune responses; however, its influence on vaccine immunogenicity is largely not well understood. Here, we examined the pivotal relationship between the mucosal microbiome and vaccine-induced immune responses by assessing longitudinal changes in vaginal and rectal microbiome profiles after intradermal immunization with a human immunodeficiency virus type 1 (HIV-1) DNA vaccine in adult rhesus macaques that received two prior DNA primes. We report that both vaginal and rectal microbiomes were dominated by Firmicutes but were composed of distinct genera, denoting microbiome specialization across mucosal tissues. Following immunization, the vaginal microbiome was resilient, except for a transient decrease in Streptococcus In contrast, the rectal microbiome was far more responsive to vaccination, exhibiting an increase in the ratio of Firmicutes to Bacteroidetes Within Bacteroidetes, multiple genera were significantly decreased, including Prevotella, Alloprevotella, Bacteroides, Acetobacteroides, Falsiporphyromonas, and Anaerocella. Decreased abundance of Prevotella correlated with induction of gut-homing α4β7+ effector CD4 T cells. Prevotella abundance also negatively correlated with rectal HIV-1 specific IgG levels. While rectal Lactobacillus was unaltered following DNA vaccination, baseline Lactobacillus abundance showed strong associations with higher rectal HIV-1 gp140 IgA induced following a protein boost. Similarly, the abundance of Clostridium in cluster IV was associated with higher rectal HIV-1 gp140 IgG responses. Collectively, these data reveal that the temporal stability of bacterial communities following DNA immunization is site dependent and highlight the importance of host-microbiome interactions in shaping HIV-1 vaccine responses. Our findings have significant implications for microbial manipulation as a strategy to enhance HIV vaccine-induced mucosal immunity.IMPORTANCE There is considerable effort directed toward evaluating HIV-1 vaccine platforms to select the most promising candidates for enhancing mucosal HIV-1 antibody. The most successful thus far, the RV144 trial provided partial protection due to waning HIV-1 antibody titers. In order to develop an effective HIV vaccine, it may therefore be important to understand how biological factors, such as the microbiome, modulate host immune responses. Furthermore, as intestinal microbiota antigens may generate antibodies cross-reactive to the HIV-1 envelope glycoprotein, understanding the relationship between gut microbiota composition and HIV-1 envelope antibody responses after vaccination is important. Here, we demonstrate for the first time in rhesus macaques that the rectal microbiome composition can influence HIV-1 vaccine immunogenicity, and we report temporal changes in the mucosal microbiome profile following HIV-1 vaccination. Our results could inform findings from the HIV Vaccine Trials Network (HVTN) vaccine studies and contribute to an understanding of how the microbiome influences HIV-1 antibody responses.

Abstract The purpose of this study was to compare the immune response generated by the intramuscular and the intradermal vaccination route against the porcine reproductive and respiratory syndrome virus (PRRSV). Piglets from a seronegative and a seropositive farm were selected (n = 28 piglets per farm), and each group was divided into two groups and vaccinated after weaning with modified live vaccine Unistrain® PRRS (Laboratorios Hipra Amer, Spain) by the intramuscular (IM) or the intradermic (ID) route. For the following 6 weeks, animals were weekly bled to assess the humoral response by PRRSV-specific antibody ELISA and viral neutralisation test. At 0-, 3-, 4- and 6 weeks post-vaccination, peripheral mononuclear blood cells (PBMC) from eight animals per group were recovered to analyse cellular response by IFN-γ ELISPOT and lymphoproliferation. Serum IL-12 was also quantified by ELISA. Seroconversion was first detected 14 days post-vaccination (dpv) for both IM and ID routes, and peaked at 35 dpv (both IM groups and ID seropositive) or 42 dpv (ID seronegative). At 3 weeks after vaccination, 6/27 (22.22%) animals from negative origin had not seroconverted, and neutralising titres were significantly lower at 35 dpv compared to the seropositive origin (mean log2 titres of 1.36 and 4.25 respectively) Also, it was 10 times more probable for them to have high levels of IL-12 a week after vaccination than for animals of seropositive origin. Cellular immune response analysed by lymphoproliferation and IFN-γ ELISPOT was already present at 21 dpv and until 42 dpv, with no significant differences between groups except for a higher lymphoproliferation at 35 dpv in the IM seropositive group (Kruskal-Wallis, p

Abstract Background Microneedles are defined as micron-sized projections with an insertion length ranging from 20 to 1500 μm and an external diameter up to 300 μm. Medications administered through microneedles diffuse through the deeper layers of the skin, into the systemic circulation, with minimal stimulation of pain-sensitive nerve endings. The rich presence of dendritic cells in the dermis makes microneedle-based vaccine delivery an attractive option. This systematic review will evaluate the efficacy and safety of intradermal delivery of vaccines using microneedles, in human beings. Methods We will search the following databases for studies reporting the efficacy and/or safety of intradermal delivery of vaccines using microneedles: Epistemonikos and the Cochrane Library for systematic reviews and MEDLINE (through PubMed), EMBASE, Cochrane CENTRAL, LIVIVO, Web of Science, Scopus and CINAHL databases for primary studies. We will also search grey literature databases and hand search reference lists of relevant studies. We will include randomised and quasi-randomised trials in human beings (any age), using microneedles (any material, length or bore) to deliver vaccines intradermally, wherein outcomes reflecting efficacy, safety, pain responses, participant satisfaction or cost are reported. We will additionally include non-randomised observational studies for long-term safety outcomes that are not reported in trials. Eligibility for inclusion will be independently determined by two reviewers. The risk of bias of the included studies will be assessed using the Cochrane RoB2 Tool (for randomised trials) and Newcastle–Ottawa Scale (for other study designs). Data on efficacy and safety will be pooled through meta-analysis (where feasible). We will explore the heterogeneity amongst randomised trials, using the Higgins and Thompson I 2 method. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on the age of participants, length of microneedle and vaccine dosage. The GRADE approach will be used to estimate the confidence in the evidence. Results This is a protocol for a systematic review; hence, there are no results at this stage. Discussion The proposed systematic review will provide evidence on efficacy, safety, pain responses, participant acceptability and cost in human beings (adults and children) for vaccines administered through the intradermal route using microneedles. Since intradermal injections using microneedles are associated with less pain due to their short lengths and narrow bores, we anticipate that delivery of vaccine antigens using this method could be a safe, efficacious and less painful alternative compared with conventional injections using hypodermic needles. The evidence in this review will be useful for policymakers, vaccine manufacturers and healthcare providers to consider this approach for the vaccination of infants and children in routine immunisation programmes. Therefore, we plan to disseminate the review through a peer-reviewed journal publication and will also provide data that cannot be included in the published version to anyone upon reasonable request. Systematic review registration PROSPERO CRD42020213608

[Display omitted] • Microparticle-based vaccine shows enhanced antigen uptake and enhanced immunogenicity. • Intradermal immunization using the ablative laser device is a pain-free method of immunization. • Intradermal immunization with ablative laser led to the generation of robust humoral and cellular responses. • A microparticulate vaccine delivered via intradermal immunization is a novel platform for vaccination and may be used for other infectious diseases. Respiratory syncytial virus (RSV) is an infectious disease that poses a significant public health risk in young children. Vaccine studies conducted in the 1960s using an intramuscular injection of formalin-inactivated respiratory syncytial virus (Fi-RSV) resulted in an enhanced respiratory disease and led to the failure of the vaccine. Thus, the virus-like particles (VLP) of the RSV fusion (F) protein was used as the vaccine antigen in this study. The F-VLP was encapsulated in a microparticle (MP) matrix composed of cross-linked bovine serum albumin (BSA) to enhance the antigen presentation and uptake. Moreover, a painless vaccination method would be desirable for an infectious disease that mainly affects young children. Thus, an ablative laser device, Precise Laser Epidermal System (P.L.E.A.S.E), was utilized to create micropores on the skin for vaccine delivery. We observed enhanced antigen presentation of the vaccine microparticles (F-VLP MP) with and without the adjuvant monophosphoryl lipid A (MPL-A) MP in dendritic cells. Consequently, Swiss Webster mice were immunized with the adjuvanted vaccine microparticles using the P.L.E.A.S.E laser to study the in vivo immunogenicity. The immunized mice had high serum immunoglobulin (IgG, IgG2a) levels, indicating a Th1 response. Subsequent analysis of lung homogenates post- RSV challenge revealed high IgA, indicating generation of a mucosal immune response upon intradermal immunization. Flowcytometry analysis showed high CD8+, and CD4+ expression in the lymph node and spleen of the adjuvanted vaccine microparticle immunized mice. Increased expression of interferon gamma (IFN-γ) in the spleen cells further proved Th1 polarized immune response. Finally, an immune plaque assay indicated significantly low lung viral titer in the mice immunized with intradermal adjuvanted vaccine microparticles. Thus, ablative laser-assisted immunization with the F-VLP based adjuvanted vaccine microparticles could be a promising vaccine candidate for RSV. [ABSTRACT FROM AUTHOR]

Simple Summary: The choice of suture material for skin closure can affect the final cosmetic outcome, the risk of wound infection and other complications in companion animals. We assessed two quickly and easily applicable skin closure methods, staples and tissue glue, and compared them to intradermal suturing in dogs, by using cosmetic, clinical, ultrasonographical and histological evaluation. The results indicate that glue had a less favorable outcome and that intradermal suture was the best, however not significantly better than staples, which are applied easier and in significantly less time. The study aimed to monitor the healing process in the canine skin following surgical incision and closure using staples or tissue glue and to compare them with the intradermal suture pattern. Surgically created skin incisions in 10 dogs were apposed with staples, tissue glue (n-butyl cyanoacrylate) and continuous intradermal pattern. The cosmetic appearance of the wounds was blindly evaluated on days 7, 14 and 28 and once a month until the end of the experiment, i.e., one year after the incision. Ultrasonographic and clinical evaluation was performed on days 0–10, 12, 14, 16, 18, 21, 24 and 28, once a week until the end of the 3rd month and once a month until the end of the experiment. Histopathological evaluation was performed on days 7, 14, 28, 180 and 365. The median time required for the performance of each technique differed significantly between techniques; stapling lasted 21 s, glue 2 min 16 s and intradermal 15 min 37 s. Cosmetic appearance with glue was statistically worse than staples and intradermal. The clinical appearance of intradermal was significantly better than glue and staples. No significant differences were found at histological evaluation; however, glue had the worst score throughout the experiment. The overall evaluation of the techniques showed that glue had the worst score compared to intradermal and staples, with the difference being statistically significant in the first postoperative week. Intradermal suture pattern is much better than glue application for skin closure in dogs, whilst is not significantly better than staples. Staples should be preferred when time is an important factor. [ABSTRACT FROM AUTHOR]

Simple Summary: The choice of suture material for skin closure can affect the final cosmetic outcome, the risk of wound infection and other complications in companion animals. We assessed two commercially available suture materials, namely, Monocryl and Securex, for use in suturing the skin of dogs, using cosmetic, clinical, ultrasonographic and histological evaluations. The results indicated only minimal differences between the two products, although better scores were achieved using Monocryl. Both were found to be sufficient for use in intradermal suturing in dogs. The earlier removal of Securex compared to Monocryl did not have any additional beneficial effect on wound healing and scar appearance in dogs. The study aimed to compare incisional wound healing with intradermal suture patterns performed with (a) absorbable suture with burying of the knots and (b) nonabsorbable suture anchored with clips. Ten dogs were included in the study. Surgically created skin incisions were apposed with continuous intradermal suture pattern with 4/0 poliglecaprone 25 with burying of the knots and continuous intradermal pattern with 4/0 polypropylene with clips. Cosmetic, clinical, ultrasonographic and histological scores were evaluated. The intradermal pattern with clips was easier to perform and required significantly less time to complete than the intradermal suture with burying of the knots. Cosmetic, clinical, ultrasonographic and histological evaluation scores did not differ significantly between the techniques. Irrespective of the technique used, the cosmetic, ultrasonographic, clinical and histological appearances of the incisions improved over time. In conclusion, polypropylene was found to be a safe and effective suture material for use with intradermal suture pattern with clips in dogs and to have an easy and quick application. However, in our sample, its earlier removal from wounds than poliglecaprone 25 was not found to be associated with a supposedly beneficial effect on wound healing and scar appearance. Both suture materials can be useful in intradermal suture techniques in dogs. [ABSTRACT FROM AUTHOR]

The advantages of skin-based vaccination include induction of strong immunity, dose-sparing, and ease of administration. Several technologies for skin-based immunisation in humans are being developed to maximise these key advantages. This route is more conventionally used in veterinary medicine. Skin-based vaccination of pigs is of high relevance due to their anatomical, physiological, and immunological similarities to humans, as well as being a source of zoonotic diseases and their livestock value. We conducted a systematic mapping review, focusing on vaccine-induced immunity and safety after the skin immunisation of pigs. Veterinary vaccines, specifically anti-viral vaccines, predominated in the literature. The safe and potent skin administration to pigs of adjuvanted vaccines, particularly emulsions, are frequently documented. Multiple methods of skin immunisation exist; however, there is a lack of consistent terminology and accurate descriptions of the route and device. Antibody responses, compared to other immune correlates, are most frequently reported. There is a lack of research on the underlying mechanisms of action and breadth of responses. Nevertheless, encouraging results, both in safety and immunogenicity, were observed after skin vaccination that were often comparable to or superior the intramuscular route. Further research in this area will underlie the development of enhanced skin vaccine strategies for pigs, other animals and humans. [ABSTRACT FROM AUTHOR]

Introduction: This phase I study explored the immunogenicity and reactogenicity of accelerated, Q7 fractional, intradermal vaccination regimens for COVID-19. Methods: Participants (n = 60) aged 18-60 years, naïve to SARS-CoV-2 infection or vaccination, were randomly allocated into one of four homologous or heterologous accelerated two-dose, two-injection intradermal regimens seven days apart:(1) BNT162b2-BNT162b2(n= 20),(2) ChAdOx1- BNT162b2 (n = 20), (3) CoronaVac-ChAdOx1 (n = 10), and (4) ChAdOx1-ChAdOx1 (n = 10). CoronaVac and ChAdOx1 were 20%, and BNT162b2 17%, of their standard intramuscular doses (0.1 mL and 0.05 mL per injection, respectively). Humoral immune responses were measured through IgG response towards receptor binding domains (RBD-IgG) of ancestral SARS-CoV-2 spike protein and pseudovirus neutralization tests (PVNT50). Cellular immune responses were measured using ELISpot for ancestral protein pools. Results: Immunogenicity was highest in regimen (2), followed by (1), (4), and (3) 2 weeks after the second dose (P < 0.001 for anti-RBD-IgG and P= 0.01 for PVNT50). Each group had significantly lower anti-RBD IgG (by factors of 5.4, 3.6, 11.6, and 2.0 for regimens (1) to (4), respectively) compared to their respective standard intramuscular regimens (P < 0.001 for each). Seroconversion rates for PVNT50 against the ancestral strain were 75%, 90%, 57% and 37% for regimens (1) to (4), respectively. All participants elicited ELISpot response to S-protein after vaccination. Adverse events were reportedly mild or moderate across cohorts. Discussion: We concluded that accelerated, fractional, heterologous or homologous intradermal vaccination regimens of BNT162b2 and ChAdOx1 were well tolerated, provided rapid immune priming against SARS-CoV-2, and may prove useful for containing future outbreaks. [ABSTRACT FROM AUTHOR]

• When delivered by VaxiPatch, a 2 µg dose of Flucelvax was comparable to IM injection. • Co-formulation of a low-dose AS01 B -like adjuvant enhanced VaxiPatch responses. • Even for adjuvanted groups, reactogenicity from patch application was negligible. • Vaccine antigens were dramatically stabilized against heat stress on VaxiPatch. All seasonal influenza vaccines for 2021–2022 in the US were quadrivalent and the market continues to be dominated by intramuscular delivery of non-adjuvanted, virion-derived antigens grown in chicken eggs. Up to four new egg-adapted production influenza vaccine strains must be generated each year. The introduction in 2012 of Flucelvax®, which is grown in mammalian suspension cell culture and uses vaccine production strains without adaptive mutations for efficient growth in eggs, represented a major advance in vaccine production technology. Here we demonstrate that Flucelvax can be reformulated and combined with a liposomal adjuvant containing QS-21 (Verndari Adjuvant System 1.1, VAS1.1) or QS-21 and 3D-PHAD (VAS1.2) for intradermal administration using a painless skin patch, VaxiPatch™. VAS1.2 is similar to AS01 B , the adjuvant system used in Shingrix® and Mosquirix™. We show that Flucelvax, when reformulated and concentrated using tangential flow filtration (TFF), maintains hemagglutination and single radial immunodiffusion (SRID) potency. Loading the reformulated Flucelvax material onto VaxiPatch arrays conferred high levels of resistance to heat stress and room temperature stability. TFF enriched vaccine antigens were combined with VAS1.1 or VAS1.2 and dispensed in 10nL drops into the pockets of 36 (total 360 nL) stainless steel microneedles arranged in a microarray 1.2 cm in diameter. Using VaxiPatch delivery of 2 µg of antigen, we demonstrated intramusuclar-comparable IgG and hemagglutination inhibition (HAI) immune responses in Sprague Dawley® rats. With addition of VAS1.2, antigen-specific IgG titers were increased as much as 68-fold (47-fold for VAS1.1) with improvements in seroconversion for three of four strains (all four were improved by VAS1.1). TFF-reformulated antigens combined with VAS1.1 or VAS1.2 and delivered by VaxiPatch showed only minor skin reactogenicity after 1 h and no skin reactogenicity after 24 h. These data indicate that VaxiPatch and the VAS system have the potential to be transformative for vaccine delivery. [ABSTRACT FROM AUTHOR]

7DW8-5 is a potent glycolipid adjuvant that improves malaria vaccine efficacy in mice by inducing IFN-γ and increasing protective CD8+ T cell responses. The addition of 7DW8-5 was previously shown to improve the efficacy of a CD8+ T cell-mediated heterologous 'prime-and-trap' malaria vaccine against Plasmodium yoelii sporozoite challenge in inbred female mice. Here, we report significant differential sex-specific responses to 7DW8-5 in inbred and outbred mice. Male mice express significantly less IFN-γ and IL-4 compared to females following intravenous 7DW8-5 administration. Additionally, unlike in female mice, 7DW8-5 did not improve the vaccine efficacy against sporozoite challenge in prime-and-trap vaccinated male mice. Our findings highlight the importance of including both female and male sexes in experimental adjuvant studies. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to investigate the effect of an intradermal (ID) administration of a PRRSV-1 modified live virus (MLV) vaccine in comparison to an intramuscular (IM) administration on health and performance. A total of 187 suckling piglets of a PRRSV-positive commercial farrow-to-finish farm were assigned to four groups: group A—PRRSV ID, group B—PRRSV IM, group C—control ID, and group D—control IM. At 2 weeks of age, all of the study piglets were either vaccinated with a PRRSV-1 MLV vaccine or injected with the vaccine adjuvant (controls). The collected blood serum samples were tested by ELISA and qRT-PCR. The side effects, body weight (BW), average daily gain (ADG), mortality rate, and lung and pleurisy lesions scores (LLS, PLS) were also recorded. Our study demonstrated that the ID vaccination of suckling piglets with a PRRSV-1 MLV vaccine has a positive effect on the piglets' health and performance, including an improved BW and a lower LLS and PLS index at their slaughter, as well as a decreased mortality rate at the growing/finishing stage. Porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in weaning and growing pigs. A vaccination against PRRSV is one of the most important control measures. This trial aimed to evaluate the effect of the intradermal (ID) administration of a PRRSV-1 modified live virus (MLV) vaccine in comparison to the intramuscular (IM) administration on the piglets' health and performance. A total of 187 suckling piglets of a PRRSV-positive commercial farrow-to-finish farm were assigned to four groups: group A—PRRSV ID, group B—PRRSV IM, group C—control ID, and group D—control IM. At 2 weeks of age, all the study piglets were either vaccinated with a PRRSV-1 MLV vaccine or injected with the vaccine adjuvant (controls). The collected blood serum samples were tested by ELISA and qRT-PCR. The side effects, body weight (BW), average daily gain (ADG), mortality rate, and lung and pleurisy lesions scores (LLS, PLS) were also recorded. The ELISA results indicated that the vaccination induced an important seroconversion at 4 and 7 weeks. Significant differences in the qRT-PCR results were noticed only at 10 weeks in group A vs. group C (p < 0.01) and group B vs. group C (p < 0.05). High viral loads, as evidenced by the qRT-PCR Ct values, were noticed in animals of both non-vaccinated groups at 7, 10, and 13 weeks. An ID vaccination has a positive impact on the BW at the piglets' slaughter, while both an ID and IM vaccination had a positive impact on the ADG. The mortality rate was lower in vaccinated groups at the finishing stage. The LLS and PLS were significantly lower in the vaccinated groups. In conclusion, our study demonstrated that the ID vaccination of suckling piglets with a PRRSV-1 MLV vaccine has a positive effect on the piglets' health and performance, including an improved BW and a lower LLS and PLS index at their slaughter, as well as a decreased mortality rate at the growing/finishing stage. [ABSTRACT FROM AUTHOR]

Shigellosis remains a global health concern, especially in low- and middle-income countries. Despite improvements in sanitation, the absence of a licensed vaccine for human use has prompted global health organizations to support the development of a safe and effective multivalent vaccine that is cost-effective and accessible for limited-resource regions. Outer Membrane Vesicles (OMVs) have emerged in recent years as an alternative to live attenuated or whole-inactivated vaccines due to their immunogenicity and self-adjuvating properties. Previous works have demonstrated the safety and protective capacity of OMVs against Shigella flexneri infection in mouse models when administered through mucosal or intradermal routes. However, some immunological properties, such as the cellular response or cross-protection among different Shigella strains, remained unexplored. In this study, we demonstrate that intradermal immunization of OMVs with needle-free devices recruits a high number of immune cells in the dermis, leading to a robust cellular response marked by antigen-specific cytokine release and activation of effector CD4 T cells. Additionally, functional antibodies are generated, neutralizing various Shigella serotypes, suggesting cross-protective capacity. These findings highlight the potential of OMVs as a promising vaccine platform against shigellosis and support intradermal administration as a simple and painless vaccination strategy to address this health challenge.

Introduction: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. Methods: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. Results. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Conclusion: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model.

The development of cross-protective vaccines against the zoonotic swine influenza A virus (swIAV), a potential pandemic-causing agent, continues to be an urgent global health concern. Commercially available vaccines provide suboptimal cross-protection against circulating subtypes of swIAV, which can lead to worldwide economic losses and poor zoonosis deterrence. The limited efficacy of current swIAV vaccines demands innovative strategies for the development of next-generation vaccines. Considering that intramuscular injection is the standard route of vaccine administration in both human and veterinary medicine, the exploration of alternative strategies, such as intradermal vaccination, presents a promising avenue for vaccinology. This investigation demonstrates the first evaluation of a direct comparison between a commercially available multivalent swIAV vaccine and monovalent whole inactivated H1N2 swine influenza vaccine, delivered by intradermal, intranasal, and intramuscular routes. The monovalent vaccines were adjuvanted with NanoST, a cationic phytoglycogen-based nanoparticle that is combined with the STING agonist ADU-S100. Upon heterologous challenge, intradermal vaccination generated a stronger cross-reactive nasal and serum antibody response in pigs compared with intranasal and intramuscular vaccination. Antibodies induced by intradermal immunization also had higher avidity compared with the other routes of vaccination. Bone marrow from intradermally and intramuscularly immunized pigs had both IgG and IgA virus-specific antibody-secreting cells. These studies reveal that NanoST is a promising adjuvant system for the intradermal administration of STING-targeted influenza vaccines.

Many vaccines require adjuvants to enhance immunogenicity, but there are few safe and effective intradermal (i.d.) adjuvants. Murine studies have validated the potency of laser illumination of skin as an adjuvant for i.d. vaccination with advantages over traditional adjuvants. We report a pilot clinical trial of low-power, continuous-wave, near-infrared laser adjuvant treatment, representing the first human trial of the safety, tolerability, and cutaneous immune cell trafficking changes produced by the laser adjuvant. In this trial we demonstrated a maximum tolerable energy dose of 300 J/cm2 to a spot on the lower back. The irradiated spot was biopsied 4 h later, as was a control spot. Paired biopsies were submitted for histomorphologic and immunohistochemical evaluation in a blinded fashion as well as quantitative PCR analysis for chemokines and cytokines. Similar to prior murine studies, highly significant reductions in CD1a+ Langerhans cells in the dermis and CD11c+ dermal dendritic cells were observed, corresponding to the increased migratory activity of these cells; changes in the epidermis were not significant. There was no evidence of skin damage. The laser adjuvant is a safe, well-tolerated adjuvant for i.d. vaccination in humans and results in significant cutaneous immune cell trafficking.-Gelfand, J. A., Nazarian, R. M., Kashiwagi, S., Brauns, T., Martin, B., Kimizuka, Y., Korek, S., Botvinick, E., Elkins, K., Thomas, L., Locascio, J., Parry, B., Kelly, K. M., Poznansky, M. C. A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.