Efficacy of Intralesional Candida Antigen Versus Measles, Mumps, and Rubella Vaccine Versus Topical Podophyllin in Treatment of Resistant Genital Warts.

BACKGROUND: No single treatment is ideal for genital warts with high rate of resistance using conventional modalities as topical podophyllin; however, several intralesional immunotherapies are being tested nowadays, with variable results. In this study, we compared the safety and efficacy of treating resistant and recurrent genital warts by 2 intralesional immunotherapies [Candida antigen and measles, mumps, and rubella (MMR) vaccine] and compared them with topical podophyllin. PATIENTS/METHODS: A total of 45 patients with resistant or recurrent genital warts were enrolled in this study. Size and number of warts were detected in each patient, patients were divided into 3 groups. Group A injected with intralesional Candida antigen. Group B with intralesional MMR vaccine. Group C were treated with topical 25% podophyllin. Patients received a session every 2 weeks for 3 treatment sessions. RESULTS: With regard to the reduction in size and number of all warts, the best response was obtained in Candida antigen group where 46.7% showed complete clearance and 40% showed partial response followed by MMR group and the last was the podophyllin group, with no significant difference between them. Complete clearance of mother warts was noticed in 86.7% of Candida group, 53.3% in MMR group, and last 40% in podophyllin group, with a significantly better response in the Candida group (P = .027). CONCLUSION: Both intralesional Candida antigen and MMR vaccine are simple, safe, and effective treatment options with comparable results and better response than topical podophyllin.

Comparative Study of Intralesional Vitamin D3 Injection and Candida Albicans Antigen in Treating Plantar Warts.

BACKGROUND: Warts, or verrucae, are mucosal human papilloma virus (HPV) infections that are very challenging to treat. OBJECTIVE: To compare the safety and efficacy of intralesional injection of vitamin D3 versus intralesional injection of candida albicans antigen for plantar warts. METHODS: Forty patients were included in the study and were divided into two groups (A&B) with 20 patients each. Group A received intralesional vitamin D3 while Group B received intralesional Candida antigen. Injection was done every 3 weeks until clearance of warts or a maximum of three treatments. RESULTS: Nine patients showed complete clearance in group A (45%), while 6 patients (30%) showed partial response and no response in 5 patients (25%) of group (A). As for group (B), complete clearance of the treated warts was observed in 8 patients (40%), partial response in 6 patients (30%) while no response was observed in 6 patients (30%). No superiority of one treatment to the other was observed nor was any statistical significance in both groups’ responses noted. CONCLUSION: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, has an excellent safety profile, with minimal recurrences and statistically equivalent. J Drugs Dermatol. 2021;20(5):546-549. doi:10.36849/JDD.5264.

Intralesional Antigen Immunotherapy in the Treatment of Periungual Warts.

BACKGROUND: Intralesional immunotherapy using different types of antigens is considered an effective and safe treatment option for different types of warts. However, there are few studies that illustrate the use of these antigens in the treatment of periungual warts as a distinct type of warts. OBJECTIVE: To evaluate the efficacy and safety of three antigens: measles, mumps, rubella (MMR) vaccine, Candida antigen, and purified protein derivative (PPD) in the treatment of periungual warts. METHODS: The study included 150 patients who were randomly assigned to 3 groups with 50 patients in each. Each agent was injected intralesionally at a dose of 0.1 mL into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. RESULTS: Complete clearance of warts was observed in 70%, 80%, and 74% in PPD, Candida antigen, and MMR vaccine groups, respectively. There was no statistically significant difference regarding the therapeutic response between the 3 studied groups. Adverse effects were transient and insignificant in the 3 groups. No recurrence of the lesions was reported in any of the studied groups. CONCLUSIONS: Intralesional antigen immunotherapy seems to be an effective therapeutic option for the treatment of periungual warts.

Intralesional Measles, Mumps, and Rubella Vaccine Versus Intralesional Candida Antigen in the Treatment of Common and Plantar Warts.

BACKGROUND: Intralesional immunotherapy has been effectively used in the treatment of warts; however, comparative studies between different antigens are limited. OBJECTIVE: To evaluate the efficacy and safety of intralesional measles, mumps, and rubella (MMR) vaccine compared with intralesional Candida antigen for the treatment of multiple common and plantar warts. METHODS: Sixty-eight adult patients with multiple common and plantar warts were randomly assigned into two groups, each containing 34 patients. The first group received intralesional MMR vaccine, while the second group received intralesional Candida antigen. Each treatment was injected into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. RESULTS: The overall therapeutic response was higher in the Candida antigen group (73.5%) compared with the MMR group (67.7%); however, the difference was not statistically significant. Complete clearance of common warts was higher in the Candida antigen group, while that of plantar warts was higher in the MMR group. Adverse effects were transient and well tolerated in both groups. No recurrence was detected during the 6-month follow-up period. CONCLUSION: Intralesional MMR and intralesional Candida antigen showed comparable efficacy and safety in the treatment of common and plantar warts.

Clinical outcomes in ocular pythiosis patients treated with a combination therapy protocol in Thailand: A prospective study.

Ocular pythiosis is the second most common form of human pythiosis, and the rates of evisceration/enucleation in Thailand are 55-79%. This prospective study was conducted to evaluate treatment outcomes of the combination therapy protocol and the potential use of serum (1→3)-ß-glucan (BG) and Pythium insidiosum-specific antibody (Pi-Ab) as an aid to diagnosis and monitoring of ocular pythiosis. Thirty patients were enrolled in the study and 14 (non-globe salvage) required evisceration/enucleation. The globe salvage group was significantly younger, and first ocular surgeries were performed significantly sooner than in the non-globe salvage group. Serum BG and Pi-Ab levels were similar among the 2 groups over time. In vitro susceptibility testing of antifungal agents revealed relatively high minimum inhibitory concentrations and lack of synergistic effect. Serum BG and Pi-Ab would not be useful in diagnosis and monitoring of ocular pythiosis. Until effective antimicrobial agents are discovered, ocular surgeries are still the mainstay therapy in Thailand.

Intralesional vitamin D3 versus Candida antigen immunotherapy in the treatment of multiple recalcitrant plantar warts: A comparative case-control study.

Intralesional immunotherapy is one of the therapeutic tools of warts. Intralesional Candida antigen was reported as successful treatment of warts. Topical and intralesional vitamin D have been used recently for wart treatment. We aim to evaluate the efficacy and safety of intralesional injection of vitamin D3 in treatment of multiple recalcitrant plantar warts in comparison with intralesional Candida antigen. Sixty patients were divided into three groups: Group I received intralesional vitamin D3, Group II intralesional Candida antigen, and Group III intralesional saline (control group). Injection was done every 3 weeks until clearance of warts or a maximum of three treatments. There was a statistically significant more reduction of warts numbers after treatment in Group I than in the other groups (p < .05). Group I showed better clinical response than Group II (p = .021). In both Groups I and II, clinical response was less favorable in patients with longer disease duration (p = .026). There was also limitation as it is a small study population. Intralesional vitamin D3 injection in multiple recalcitrant plantar warts is a simple, safe, cost effective treatment modality with minimal side effects, and superior results compared with intralesional injection of Candida antigen.

Peripheral blood toll-like receptor 4 correlates response to candida immunotherapy of warts.

Human papilloma virus infection may be self-limiting; however, some cases may spread. There are no factors predicting the prognosis of such infections. The present study aimed to evaluate the significance of TLR4 expression in predicting the response of warts to candida immunotherapy. A total of 60 patients with different types of warts were included in the present study. A total volume of 2 ml venous blood was collected and real-time polymerase chain reaction was used to determine expression of TLR4. Patients were subjected to intralesional injection of Candida antigen into the largest wart at 2-week intervals until complete clearance or for a maximum of six sessions. Of the total 58 patients available for analysis of study results, 44 patients (75.9%) showed complete resolution with better response in younger ages. The TLR4 expression in patients with complete and partial response was significantly higher than that in patients who had no response (p = .006). Among our patients, 48.3% showed no side effects, 44.8% showed local reactions, and 6.9% showed systemic side effects. Only four patients showed recurrence after 6 months. Using receiver operating characteristic curve analysis, at cutoff of expression level >12 is accompanied by 100% specificity of TLR4 in predicting treatment response to candida immunotherapy. Candida immunotherapy is an effective warts treatment, especially in young patients. Higher PMBC TLR4 levels can predict response to candida immunotherapy.

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii.

Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4+ T cells were depleted, and the mice were exposed to Pneumocystis murina Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii Potential orthologs of Pca1 have been identified in P. jirovecii Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.

Uveitis Following Treatment of Verruca Vulgaris with Intralesional Candida Antigen.

This is a first literature report of a case of uveitis along with severe systemic symptoms following verruca vulgaris treatment with intralesional Candida antigen. We believe the Candida injection was causative.

[THE CORRECTION OF THE LOCAL IMMUNE RESPONSE AT THE PATIENTS WITH HELICOBACTER PYLORI INFECTION].

INTRODUCTION: Helicobacter pylori infection is due to the high prevalence in population attracts the clinical interest of researchers in the whole World. It is well known that this microorganism not only resides in the mucosa of the gastrointestinal tract, but is also defined in the periodontal pocket of the oral cavity. THE AIM OF INVESTIGATION: to evaluate Helicobacter pylori diagnostics in the mouth and prove a method of relief of the inflammatory process by applying immunomodulator Imudon. RESULTS. On the basis of obtained results it was found that the inclusion of topical immunomodulator Imudon in the complex therapy of Helicobacter pylori-associated diseases leads to reduction of inflammatory potential through the decrease of the TNFα, IL-6 activity in saliva and to increase the protective properties of saliva as a result of increased levels of mucin, significantly reduces the frequency of relapses in the one year after therapy. CONCLUSION: It is practically important to determine the effectiveness of eradication therapy by the study of the contents of the tooth-gingival pocket for the detection of genetic material of Helicobacter pylori, as well as to include in the complex therapy of Helicobacter pylori-associated diseases of the immune modulator Imudon.

Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model.

BACKGROUND: In susceptible individuals, exposure to Aspergillus fumigatus can lead to the development of atopic lung diseases such as allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). Protease allergens including Asp f 5 and Asp f 13 from Aspergillus fumigatus are thought to be important for initiation and progression of allergic asthma. OBJECTIVE: To assess the importance of secreted protease allergens Asp f 5 (matrix metalloprotease) and Asp f 13 (serine protease) in Aspergillus fumigatus-induced inflammation, airway hyperactivity, atopy and airway wall remodelling in a murine model following chronic exposure to secreted allergens. METHODS: BALB/c mice were repeatedly intranasally dosed over the course of 5 weeks with culture filtrate from wild-type (WT), Asp f 5 null (∆5) or Asp f 13 null (∆13) strains of Aspergillus fumigatus. Airway hyper-reactivity was measured by non-invasive whole-body plethysmography, Th2 response and airway inflammation by ELISA and cell counts, whilst airway remodelling was assessed by histological analysis. RESULTS: Parent WT and ∆5 culture filtrates showed high protease activity, whilst protease activity in ∆13 culture filtrate was low. Chronic intranasal exposure to the three different filtrates led to comparable airway hyper-reactivity and Th2 response. However, protease allergen deleted strains, in particular ∆13 culture filtrate, induced significantly less airway inflammation and remodelling compared to WT culture filtrate. CONCLUSION: Aspergillus fumigatus-secreted allergen proteases, Asp f 5 and Asp f 13, are important for recruitment of inflammatory cells and remodelling of the airways in this murine model. However, deletion of a single allergen protease fails to alleviate airway hyper-reactivity and allergic immune response. Targeting protease activity of Aspergillus fumigatus in conditions such as SAFS or ABPA may have beneficial effects in preventing key aspects of airway pathology.

Synthesis and immunological studies of linear oligosaccharides of ß-glucan as antigens for antifungal vaccine development.

Antifungal vaccines have recently engendered considerable excitement for counteracting the resurgence of fungal infections. In this context, ß-glucan, which is abundantly expressed on all fungal cell surfaces, functionally necessary for fungi, and immunologically active, is an attractive target antigen. Aiming at the development of effective antifungal vaccines based on ß-glucan, a series of its oligosaccharide derivatives was designed, synthesized, and coupled with a carrier protein, keyhole limpet hemocyanin (KLH), to form new semisynthetic glycoconjugate vaccines. In this article, a convergent and effective synthetic strategy using preactivation-based iterative glycosylation was developed for the designed oligosaccharides. The strategy can be widely useful for rapid construction of large oligo-ß-glucans with shorter oligosaccharides as building blocks. The KLH conjugates of the synthesized ß-glucan hexa-, octa-, deca-, and dodecasaccharides were demonstrated to elicit high titers of antigen-specific total and IgG antibodies in mice, suggesting the induction of functional T cell-mediated immunity. Moreover, it was revealed that octa-, deca-, and dodeca-ß-glucans were much more immunogenic than the hexamer and that the octamer was the best among these. The results suggested that the optimal oligosaccharide sequence of ß-glucan required for exceptional immunogenicity was a hepta- or octamer and that longer glucans are not necessarily better antigens, a finding that may be of general importance. Most importantly, the octa-ß-glucan-KLH conjugate provoked protective immunity against Candida albicans infection in a systemic challenge model in mice, suggesting the great potential of this glycoconjugate as a clinically useful immunoprophylactic antifungal vaccine.

TLR9-dependent IL-23/IL-17 is required for the generation of Stachybotrys chartarum-induced hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that develops after repeated exposure to inhaled particulate Ag. Stachybotrys chartarum is a dimorphic fungus that has been implicated in a number of respiratory illnesses, including HP. In this study, we have developed a murine model of S. chartarum-induced HP that reproduces pathology observed in human HP, and we have hypothesized that TLR9-mediated IL-23 and IL-17 responses are required for the generation of granulomatous inflammation induced by inhaled S. chartarum. Mice that undergo i.p. sensitization and intratracheal challenge with 10(6) S. chartarum spores developed granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of T cells. S. chartarum sensitization and challenge resulted in robust pulmonary expression of IL-17 and IL-23. S. chartarum-mediated granulomatous inflammation required intact IL-23 or IL-17 responses and required TLR9, because TLR9(-/-) mice displayed reduced IL-17 and IL-23 expression in whole lung associated with decreased accumulation of IL-17 expressing CD4(+) and γδ T cells. Compared with S. chartarum-sensitized dendritic cells (DC) isolated from WT mice, DCs isolated from TLR9(-/-) mice had a reduced ability to produce IL-23 in responses to S. chartarum. Moreover, shRNA knockdown of IL-23 in DCs abolished IL-17 production from splenocytes in response to Ag challenge. Finally, the intratracheal reconstitution of IL-23 in TLR9(-/-) mice recapitulated the immunopathology observed in WT mice. In conclusion, our studies suggest that TLR9 is critical for the development of Th17-mediated granulomatous inflammation in the lung in response to S. chartarum.

Intralesional Candida Antigen Immunotherapy for the Treatment of Recalcitrant and Multiple Warts in Children.

BACKGROUND: Intralesional injection of Candida antigen appears to be an effective alternative for the treatment of warts. AIM: To determine the efficacy and safety of this treatment. METHODS: We retrospectively reviewed records of all children who received intralesional injection of Candida antigen at our center from January 2008 to July 2013. RESULTS: From a total of 220 patients, 156 (70.9%) had a complete response, 37 (16.8%) had a partial response, and 27 (12.2%) had no improvement. An average of 2.73 treatments was needed. Forty-seven of the patients with more than one wart (21.3%) also noted at least partial resolution of untreated warts at distant sites. Twenty-seven of the 47 patients (57.4%) had complete resolution. All treated patients experienced some discomfort at the time of the injection, but no serious side effects were reported. DISCUSSION: We report our results using this approach in a large group of children. CONCLUSION: Intralesional injection of Candida antigen is an effective and safe therapy for children with multiple and recalcitrant cutaneous warts.

Distinct and complementary roles for Aspergillus fumigatus-specific Tr1 and Foxp3+ regulatory T cells in humans and mice.

Unlike induced Foxp3(+) regulatory T cells (Foxp3(+) iTreg) that have been shown to play an essential role in the development of protective immunity to the ubiquitous mold Aspergillus fumigatus, type-(1)-regulatory T cells (Tr1) cells have, thus far, not been implicated in this process. Here, we evaluated the role of Tr1 cells specific for an epitope derived from the cell wall glucanase Crf-1 of A. fumigatus (Crf-1/p41) in antifungal immunity. We identified Crf-1/p41-specific latent-associated peptide(+) Tr1 cells in healthy humans and mice after vaccination with Crf-1/p41+zymosan. These cells produced high amounts of interleukin (IL)-10 and suppressed the expansion of antigen-specific T cells in vitro and in vivo. In mice, in vivo differentiation of Tr1 cells was dependent on the presence of the aryl hydrocarbon receptor, c-Maf and IL-27. Moreover, in comparison to Tr1 cells, Foxp3(+) iTreg that recognize the same epitope were induced in an interferon gamma-type inflammatory environment and more potently suppressed innate immune cell activities. Overall, our data show that Tr1 cells are involved in the maintenance of antifungal immune homeostasis, and most likely play a distinct, yet complementary, role compared with Foxp3(+) iTreg.

µ-chain-deficient mice possess B-1 cells and produce IgG and IgE, but not IgA, following systemic sensitization and inhalational challenge in a fungal asthma model.

Allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. This study assessed the requirement for B cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. C57BL/6 and µMT mice (assumed to lack peripheral B cells) were sensitized with Aspergillus fumigatus extract and challenged with two inhalation exposures of live conidia to induce airway disease. Airway hyperresponsiveness after methacholine challenge, peribronchovascular inflammation, goblet cell metaplasia, and fibrotic remodeling of the airways was similar between µMT mice and their wild-type counterparts (C57BL/6). Surprisingly, even in the absence of the µ-chain, these µMT mice produced IgE and IgG Abs, although the Abs induced did not have specificity for A. fumigatus Ags. In contrast, IgA was not detected in either the lavage fluid or serum of µMT mice that had been exposed to A. fumigatus. Our findings also reveal the existence of CD19(+)CD9(+)IgD(+) B-1 cells in the lungs of the µMT animals. These data show the µMT mice to have a developmental pathway independent of the canonical µ-chain route that allows for their survival upon antigenic challenge with A. fumigatus conidia, although this pathway does not seem to allow for the normal development of Ag-specific repertoires. Additionally, this study shows that IgA is not required for either clearance or containment of A. fumigatus in the murine lung, as fungal outgrowth was not observed in the µMT animals after multiple inhalation exposures to live conidia.

Bronchial inflammation in hypersensitivity pneumonitis after antigen-specific inhalation challenge.

BACKGROUND AND OBJECTIVE: The aim of this study is to compare the inflammatory profile before and after specific inhalation challenge (SIC) in induced sputum from patients with hypersensitivity pneumonitis (HP) and to investigate whether different causal antigens define the resulting profile. METHODS: A prospective study was conducted in 27 patients with HP: 15 patients due to exposure to birds (BHP) and 12 due to exposure to fungi (FHP), confirmed by SIC. Induced sputum was obtained before and/or 24 h after SIC. Cell types were determined by differential cell count using optical microscopy. Interferon-γ, interleukin (IL)-12p70, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1ß, tumour necrosis factor (TNF)-α and TNF-ß levels were measured in the supernatants. RESULTS: Following SIC, higher sputum neutrophilia levels (P = 0.048) and an increase in IL-8 levels (P = 0.017) were found in patients with FHP than in those with BHP. FHP patients also showed increased IL-1ß, IL12-p70 and IL5 levels (P = 0.011, P = 0.036 and P = 0.018, respectively) after SIC. In BHP, a trend towards increases in sputum eosinophils and TH2 cytokines (IL4, IL5) was seen following SIC (P = 0.059, P = 0.068 and P = 0.075 respectively). CONCLUSIONS: This study shows that bronchial inflammation is present in patients with HP evidenced by increases in sputum neutrophils and eosinophils following exposure to the offending antigen during SIC.

Immunization with P10 peptide increases specific immunity and protects immunosuppressed BALB/c mice infected with virulent yeasts of Paracoccidioides brasiliensis.

Paracoccidioidomycosis is a systemic granulomatous disease caused by Paracoccidioides spp. A peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4(+) helper-1 immune response in mice and protects against intratracheal challenge with virulent P. brasiliensis. Previously, we evaluated the efficacy of the P10 peptide alone or combined with antifungal drugs in mice immunosuppressed and infected with virulent isolate of P. brasiliensis. In the present work, our data suggest that P10 immunization leads to an effective cellular immune response associated with an enhanced T cell proliferative response. P10-stimulated splenocytes increased nitric oxide (NO) production and induced high levels of IFN-γ, IL-1ß and IL-12. Furthermore, significantly increased concentrations of pro-inflammatory cytokines were also observed in lung homogenates of immunized mice. P10 immunization was followed by minimal fibrosis in response to infection. Combined with antifungal drugs, P10 immunization most significantly improved survival of anergic infected mice. Administration of either itraconazole or sulfamethoxazole/trimethoprim together with P10 immunization resulted in 100 % survival up to 200 days post-infection, whereas untreated mice died within 80 days. Hence, our data show that P10 immunization promotes a strong specific immune response even in immunocompromised hosts and thus P10 treatment represents a powerful adjuvant therapy to chemotherapy.