Misdiagnosed centipede and scorpion poisoning characterized by delayed hypersensitivity reaction: A case report.

RATIONALE: Traditional Chinese medicine is widely used in China and Asian countries. According to the traditional Chinese medicine theory, centipedes and scorpions have the functions of relaxing spasm, eliminating masses, relieving pain, and dredging meridians and collaterals. Improper medication can lead to serious adverse reactions. PATIENT CONCERNS: One 38-years-old female presented to our hospital because of cough and fever for more than 10 days. Ineffective anti-infection treatment, delayed skin rashes and supplementary medical history guided us to take centipede and scorpion poisoning into consideration. DIAGNOSES: Delayed hypersensitivity caused by centipedes and scorpions. INTERVENTIONS: Anti-allergic therapy with glucocorticoid (methylprednisolone 40 mg/day) and H1 receptor antagonists (loratadine 10 mg/day). OUTCOMES: During the 1 year follow-up revealed, no fever, rash and any discomfort occurred. LESSONS: This case suggests that because oral Chinese medicine poisoning is rare, detailed collection of medical history is particularly important for poisoning diagnosis.

Massive bee envenomation treated by therapeutic plasma exchange.

In the unfortunate event of massive envenomation and precipitation of multiorgan failure, therapeutic plasma exchange (TPE) can be considered as a modality for therapy. We present a patient case where TPE potentially allowed for removal of toxin with subsequent clinical improvement.

Germinated black soybean fermented with Lactobacillus pentosus SC65 alleviates DNFB-induced delayed-type hypersensitivity in C57BL/6N mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhynchosia nulubilis (black soybean) has many applications in oriental medicine. It is traditionally used to treat disease related with high blood pressure, diabetes, inflammation, and osteoporosis. Furthermore, fermented soybean foods have traditionally been used for immunity enhancement in East Asia. However, the anti-inflammatory effects of germinated R. nulubilis (GR) against delayed-type hypersensitivity (DTH) are not fully understood. AIM OF STUDY: This study aimed to investigate the anti-inflammatory effects of germinated Rhynchosia nulubilis (GR) fermented with the lactic acid bacterium Lactobacillus pentosus SC65 (GR-SC65) isolated from pickled burdock. MATERIALS AND METHODS: We investigated the effects of GR-SC65 (300 mg/kg/day) on ear thickness and immune cell infiltration in DNFB-induced DTH in mice. We used dexamethasone (3 mg/kg) as a reference drug. Changes in infiltration of CD4+ and CD8+ T cells and NK cells were examined by immunohistochemistry. In addition, we investigated cytokine and chemokine production related to DTH using reverse transcription-polymerase chain reaction. We also investigated DTH-related cytokine production using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. RESULTS: Two lactic acid bacterial strains (Lactobacillus pentosus SC65 and Pediococcus pentosaceus ON81A) were selected for fermenting GR due to their high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. The total polyphenol contents (TPCs) in GR-SC65 and GR-ON81A were higher than that in unfermented GR (∗∗∗P < 0.001 vs. GR). Content of daidzein, glycitein, and genistein, the deglycosylated form of isoflavonoids, was higher in GR-SC65 than in unfermented GR. The ethanol extracts of GR-SC65 exerted a stronger anti-inflammatory activity than GR by inhibiting pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in LPS-induced RAW264.7 macrophages. GR-SC65 reduced 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced ear swelling and hyperplasia as well as vascular permeability. Fewer infiltrated CD4+ and CD8+ T cells were observed in the ear tissue of the GR-SC65-treated mice than those of the unfermented GR-treated mice. Furthermore, fewer infiltrated NK cells were observed in the GR-SC65 treated mice, than in the GR-treated mice. GR-SC65 significantly diminished the levels of CCL5 and COX-2 mRNAs and increased the level of IL-10 mRNA. CONCLUSIONS: These data suggest that GR-SC65 can be used as a health supplement or a prophylactic against delayed-type hypersensitive inflammatory disease.

Jianqu fermentation with the isolated fungi significantly improves the immune response in immunosuppressed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianqu, a classical formula of traditional Chinese medicine, is used clinically to treat symptoms like chill and fever headache, diarrhea and loss of appetite and act on patients with low immunity. However, the quality control of Jianqu fermentation is not well established, and its function in regulating the body's immunity still remains unclear. AIM OF THE STUDY: The present study firstly assesses the structure and diversity of fungal community during Jianqu fermentation and then investigates the immune regulating function of Jianqu extract in mouse model. MATERIALS AND METHOD: The high-throughput sequencing is conducted to analyze the diversity and distribution of fungal community during the fermentation process of Jianqu, and then fungi with a high frequency and relative abundance are isolated. The immunosuppressed mice are induced by using cyclophosphamide (CTX) and used to evaluate the immune regulating function of Jianqu extract from natural fermentation or directed fermentation, respectively. RESULTS: With the fermentation, the diversity and distribution of fungal community significantly changed. The number of OTU (operational taxonomic unit) was gradually decreased from 223 ± 1 in the early phase to 201 ± 11 in the middle phase and to 175 ± 32 in the later phase of Jianqu fermentation. Generally, in genus level, Millerozyma, Debaryomyces and Rhizomucor showed a significant increase and became dominant in the mid or later phase of fermentation, while the Aspergillus displayed a decrease following the fermentation. However, Saccharomycopsis is a dominate species in surveyed samples. Next, six fungi strains with a high frequency and relative abundance, including Saccharomycopsis fibuligera, Millerozyma farinose, Hyphopichia burtonii, Rhizomucor pusillus, Lichtheimia ramosa, and Monascus purpureus, are isolated successfully. Interestingly, directed fermentation for Jianqu with the six isolated fungi strains could achieve similar morphological characteristics with the natural fermentation. Consistently, Jianqu extract from directed fermentation demonstrated a similar therapeutic effect on immune response as that of naturally fermented Jianqu. CONCLUSIONS: We firstly showed the significant change of structural profiles of fungal communities during Jianqu fermentation, and successfully isolated six dominate fungi strains in Jianqu. Interestingly, directed fermentation for Jianqu with these isolated strains could achieve a similar morphological characteristics and immune-modulating function as natural fermentation. It was suggested that Jianqu fermentation with functional fungi instead of natural microbes provide a new approach for the improvement of the production and quality control of the traditional Chinese medicine of Jianqu.

Jellyfish anaphylaxis: A wide spectrum of sensitization routes.

Background: Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. Objective: The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. Methods: We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words "jellyfish" associated with "anaphylaxis" or "anaphylactic shock." Results: The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Conclusion: Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by cross-reactivity.

Increase in concentration of patch test allergen reduces patch test occlusion time to 12 hours without affecting patch test reactivity in patients with parthenium dermatitis.

BACKGROUND: Patch testing is the standard method to diagnose contact allergy. Patches are applied for 48 hours, which is inconvenient to patients in tropical weather. Therefore, we evaluated different patch test occlusion times with increased concentrations of an allergen to determine if occlusion time can be reduced without compromising patch test reactivity. METHODS: Patch test positive patients with parthenium dermatitis were enrolled and patch tested using five different concentrations (10%, 4%, 2%, 1%, and 0.5%) of parthenium extract. The patches were applied in triplicate. The first set was removed after 12 hours, whereas the second and third sets were removed after 24 and 48 hours, respectively. Readings were performed at 24, 48, and 96 hours. RESULTS: Fifty patients with parthenium dermatitis were included. The positive patch test reaction rates were comparable in all three sets at 24- and 48-hour readings irrespective of the occlusion time. All were positive, with 10%, 4%, and 2% concentrations at 96-hour reading with an occlusion time of 12 hours. CONCLUSION: An occlusion time of 12 hours seems adequate to elicit positive patch test reaction at a 96-hour reading if the concentration of patch test allergen can be increased, that is, from 1% to 2% in these patients.

Enhancement of adaptive immune responses of aged mice by dietary intake of ß-glucans, with special emphasis on anti-aging activity.

The naturally occurring polysaccharide, ß-1,3-glucans, a well-known immunostimulant, has been highly valued for many years for their health-promoting and anti-aging properties, but its mode of action is poorly understood. In this study, we first showed that oral administration of ß-1,3-glucans did not affect the general condition and physiology of male mice throughout the trial period. We then showed that dietary intake of ß-1,3-glucans induced a significant increase in T helper cells (CD4+) in young, middle-aged and aged male mice. We also showed that ß-1,3-glucans supplementation considerably increased the delayed-type hypersensitivity (DTH) response, a T cell-mediated immune response, in young and aged mice. In addition, we found that ß-1,3-glucans supplementation remarkably promoted the production of total anti-keyhole limpet hemocyanin (KLH) immunoglobulin G (IgG), anti-KLH IgG1, and anti-KLH IgG2a in young and aged mice without disturbing immune homeostasis. These data together indicate that oral administration of ß-1,3-glucans enhanced the adaptive immune responses of aged mice without disturbing their general condition and physiology, supporting the idea that ß-1,3-glucans are capable of counteracting the immunosenescence in mice. They also suggest that ß-1,3-glucans can be clinically useful to help the elderly generate an improved response to vaccine with stronger humoral and cell-mediated immune responses.

Cysteine-type cathepsins promote the effector phase of acute cutaneous delayed-type hypersensitivity reactions.

Cysteine-type cathepsins such as cathepsin B are involved in various steps of inflammatory processes such as antigen processing and angiogenesis. Here, we uncovered the role of cysteine-type cathepsins in the effector phase of T cell-driven cutaneous delayed-type hypersensitivity reactions (DTHR) and the implication of this role on therapeutic cathepsin B-specific inhibition. Methods: Wild-type, cathepsin B-deficient (Ctsb-/-) and cathepsin Z-deficient (Ctsz-/-) mice were sensitized with 2,4,6-trinitrochlorobenzene (TNCB) on the abdomen and challenged with TNCB on the right ear to induce acute and chronic cutaneous DTHR. The severity of cutaneous DTHR was assessed by evaluating ear swelling responses and histopathology. We performed fluorescence microscopy on tissue from inflamed ears and lymph nodes of wild-type mice, as well as on biopsies from psoriasis patients, focusing on cathepsin B expression by T cells, B cells, macrophages, dendritic cells and NK cells. Cathepsin activity was determined noninvasively by optical imaging employing protease-activated substrate-like probes. Cathepsin expression and activity were validated ex vivo by covalent active site labeling of proteases and Western blotting. Results: Noninvasive in vivo optical imaging revealed strong cysteine-type cathepsin activity in inflamed ears and draining lymph nodes in acute and chronic cutaneous DTHR. In inflamed ears and draining lymph nodes, cathepsin B was expressed by neutrophils, dendritic cells, macrophages, B, T and natural killer (NK) cells. Similar expression patterns were found in psoriatic plaques of patients. The biochemical methods confirmed active cathepsin B in tissues of mice with cutaneous DTHR. Topically applied cathepsin B inhibitors significantly reduced ear swelling in acute but not chronic DTHR. Compared with wild-type mice, Ctsb-/- mice exhibited an enhanced ear swelling response during acute DTHR despite a lack of cathepsin B expression. Cathepsin Z, a protease closely related to cathepsin B, revealed compensatory expression in inflamed ears of Ctsb-/- mice, while cathepsin B expression was reciprocally elevated in Ctsz-/- mice. Conclusion: Cathepsin B is actively involved in the effector phase of acute cutaneous DTHR. Thus, topically applied cathepsin B inhibitors might effectively limit DTHR such as contact dermatitis or psoriasis. However, the cathepsin B and Z knockout mouse experiments suggested a complementary role for these two cysteine-type proteases.

Rotavirus Double Infection Model to Study Preventive Dietary Interventions.

Rotaviruses are the main cause of acute diarrhea among young children worldwide with an increased frequency of reinfection. Several life style factors, such as dietary components, may influence such processes by affecting the outcome of the first rotavirus infection and therefore having a beneficial impact on the anti-rotavirus immune responses during any subsequent reinfections. The aim of this research was to develop a double-infection model in rat that mimics real-life clinical scenarios and would be useful in testing whether nutritional compounds can modulate the rotavirus-associated disease and immune response. Three experimental designs and a preventive dietary-like intervention were conducted in order to achieve a differential response in the double-infected animals compared to the single-infected ones and to study the potential action of a modulatory agent in early life. Diarrhea was only observed after the first infection, with a reduction of fecal pH and fever. After the second infection an increase in body temperature was also found. The immune response against the second infection was regulated by the preventive effect of the dietary-like intervention during the first infection in terms of specific antibodies and DTH. A rotavirus-double-infection rat model has been developed and is suitable for use in future preventive dietary intervention studies.

Improvement of glucocorticoid-impaired thymus function by dihydromyricetin via up-regulation of PPARγ-associated fatty acid metabolism.

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. In the current study, we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T cell numbers in thymus which was effectively improved by co-treatment with DMY. Quantification of signal joint TCR delta excision circles (TRECs) and Vß TCR spectratyping analysis were employed to determine the thymus function with indicated treatments. The results showed that DEX-impaired thymus output and decreased TCR cell diversity which was ameliorated by co-treatment with DMY. iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of mice treated with or without indicated agents, followed by informatics analysis to identify the correlated signaling pathway. After validated by Western blotting and Real-time PCR, we found that PPARγ-associated fatty acid metabolism was increased in the thymic tissues of the animals treated with DMY plus DEX than the animals treated with DEX alone. The agonist and antagonist of PPARγ were further employed to verify the role of PPARγ in the present study. Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX on suppressing inflammation in vivo. Collectively, DMY relieved thymus function damaged by DEX via regulation of PPARγ-associated fatty acid metabolism. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate adjuvant natural agents through up-regulation of PPARγ-associated fatty acid metabolism.

Immunological In Vivo and In Vitro Investigations of Aqueous Extract of Stem Bark of Pterocarpus erinaceus Poir (Fabaceae).

BACKGROUND: Macrophages are the first cells to recognize invading foreign bodies and are central to cell mediated and humoral immunity. Therefore, the activation of macrophages is a key event for effective innate and adaptive immunity. Pterocarpus erinaceus has been reported to control infectious diseases, but the mechanism remains to be elucidated. In this study, we demonstrated the immune-modulatory effect of aqueous extract of P. erinaceus using human macrophages and lymphocytes, as well as mice. METHODS: Hot water was used to extract P. erinaceus from the stem bark. Its effect on lymphocytes was measured by evaluating proliferative response and delayed hypersensitivity. Phagocytic activity of macrophages were measured based on neutral red uptake assay, nitric oxide production and myeloperoxidase and phosphatase acid activity. Hematopoietic and infectious activities were analyzed using the effect on infectious stress and chloramphenicol-induced leucopenic mice model. RESULTS: Aqueous extract showed stronger stimulatory effects on the neutral red uptake, production of nitric oxide and phosphatase acid activity in lipopolysaccharide-activated macrophages. In addition, aqueous extract significantly stimulated the proliferation of phytohemagglutinin-activated lymphocytes, enhanced delayed hypersensitivity response to erythrocytes and attenuated infection-induced fever. Furthermore, aqueous extract also significantly increased the rate of recovery of white blood cell levels in chloramphenicol-induced leucopenia mice. CONCLUSIONS: The results suggest that aqueous extract of P. erinaceus stem bark is able to modulate the immune system and has potential effects in clinical conditions when an immune-enhancing and anti-infectious effect is desired.

The Incidence of Delayed-Type Hypersensitivity Reactions to Apples Among Patients Allergic to Birch Pollen

The major apple allergen Mal d 1 cross-reacts with the homologous birch pollen allergen Bet v 1 and causes immunoglobulin E (IgE)-mediated immediate-type allergic reactions. In some patients, delayed-type hypersensitivity to apples may develop within 72 hours without evidence of specific IgE or a positive skin prick test (SPT). The aim of the study was to evaluate the concomitance of delayed-type hypersensitivity reactions and immediate IgE-mediated reactions against high- and low-allergenic apple cultivars in patients with birch pollen allergy. Data were obtained from 45 adults with clinical symptoms of birch pollen allergy. Patients were exposed to apple pulp via atopy patch tests (APTs) and SPTs. Levels of IgE specific to Bet v 1 and Mal d 1 were measured with a radioallergosorbent test. Patients allergic to birch pollen showed the highest rate of positive SPT responses to Golden Delicious apples and the lowest rate to low-allergenic cultivar Grey French Reinette. Among these patients, 9% developed delayed hypersensitivity reactions to either Golden Delicious or Grey French Reinette apples; these reactions manifested clinically as erythema with papules (class ++). Fifty percent of APT-positive patients were concomitantly SPT-negative. Here, we show for the first time the clinical relevance of T cell-driven allergic reactions to apples. APTs may reveal type IV sensitization in patients who are negative for the corresponding type I sensitization tests. Thus, utilization of the APT procedure with fresh apple appears to be a valuable tool for the diagnosis of apple allergy and may improve the accuracy of food allergy diagnoses.

Polymorphous Light Eruption.

Polymorphous light eruption (PLE) is the commonest immuno-mediated photodermatosis. It occurs after solar or artificial UV-light exposure and affects only the sun-exposed areas with preference of the V-area of the chest, of arms and forearms, legs, upper part of the back, and rarely the face. The lesions are itching or burning, and vary morphologically from erythema to papules, vesico-papules and occasionally blisters, plaques, sometimes erythema multiforme-like, insect bite-like wheals and purpura. The clinical manifestations befall within a few hours to days from light exposure, last a few days, and subside in about a week without sequelae. Its diagnosis is based on history, morphology and phototests. PLE is considered as a delayed hypersensitivity response to newly UV induced, but still unidentified, antigen(s). Usually, MED is normal, but the provocative phototests with UVA or UVB reproduce the spontaneous lesions in about 50% of the patients. Broad spectrum sunscreens and antioxidants, photohardening with PUVA or narrow band UVB may be beneficial to prevent the disease. Therapy is based mainly on topical or systemic corticosteroids.

Latex proteins from Calotropis procera: Toxicity and immunological tolerance revisited.

Many thousands of plants are disseminated worldwide in traditional and folk medicines based on the belief that their leaves, roots, seeds, bark or secretions, when adequately handled, can treat, alleviate or ameliorate numerous disease symptoms. Calotropis procera (Apocynaceae) is a popular medicinal plant and the claims of this shrub's phytomedicinal properties have been scientifically validated. In this study, further prospects towards the in vivo toxicity and oral immunological tolerance of phytomodulatory proteins isolated from the latex of C. procera are reported. Acute toxicity was determined in mice by oral and intraperitoneal administration of latex proteins (LP) and was followed behavioral, hematological and histological analyses. Oral immunological tolerance to LP was assessed by intraperitoneal immunization in mice that had received LP orally before. Animals given 5000 mg/kg orally exhibited only discrete behavioral alterations and augmentation of monocytes. Death was not notified 14 days after exposure. However, all animals receiving LP 150 mg/kg by i.p. died in 1 h. Death (20%) was documented when LP (75 mg/kg) was given in the peritoneum and signs of harmful effects were observed in the survivors (80%). Oral immunological tolerance was observed in animals previously given LP orally, when they were further immunized/challenged with peritoneal exposure to different doses of LP. This was confirmed by the lowering of IgE and IgG in the serum, IL-4 and IFN-γ in spleen homogenates and the absence of anaphylaxis signs. It is therefore concluded that LP exhibited quite discrete adverse effects when orally administrated at higher concentrations and this route of administration did not stimulate adverse immunological reactions. Instead it was observed immunological tolerance. The present study contributes very important information concerning the safe use of C. procera as a phytotherapeutic agent.

Primary Cell Phenotypic Screening Illuminates ADRs and AOPs.

Preclinical, in vitro screening for adverse drug reactions continues to present challenges in the field of drug development. In this issue of Cell Chemical Biology, Shah et al. (2017) employ a phenotypic screening strategy using a panel of human primary cells to define a signature response and an adverse outcome pathway for delayed type IV skin hypersensitivity.

Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog.

Effector memory T lymphocytes (TEM cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The Kv1.3 potassium channel is a key regulator of CCR7- TEM cell activation. Blocking Kv1.3 inhibits TEM cell activation and attenuates inflammation in autoimmunity, and as such, Kv1.3 has emerged as a promising target for the treatment of TEM cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent Kv1.3 blockers and HsTX1[R14A] is selective for Kv1.3 over closely-related Kv1 channels. PEGylation of HsTX1[R14A] to create a Kv1.3 blocker with a long circulating half-life reduced its affinity but not its selectivity for Kv1.3, dramatically reduced its adsorption to inert surfaces, and enhanced its circulating half-life in rats. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7- TEM cell proliferation, leaving CCR7+ naïve and central memory T cells able to proliferate. It reduced inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduced inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases. PEG-HsTX1[R14A] has the additional advantages of reduced non-specific adsorption to inert surfaces and enhanced circulating half-life.

Immunomodulatory Study of Different Solvent Extract of Elephantopus scaber Linn.

The aim and objective of present study is that to provide a scientific evidence for the immunomodulatory potential of Elephantopus scaber in vivo. The immunomodulatory activity was performed in petroleum ether, solvent ether, methanol and aqueous extract of aerial part and root of E. scaber by using models such as delayed type hypersensitivity, humoral antibody response to SRBC and carbon clearance test for phagocytic activity in Wistar rat. The observation and results of present study suggested that among the total 8 extract, only the petroleum ether and solvent ether aerial part extract of E. scaber significantly decreased in delayed type hypersensitivity (DTH), humoral antibody (HA) titre and phagocytic index thereby indicating significant immunosuppressant activity in experimental animals.

A novel preservative-free seasonal influenza vaccine safety and immune response study in the frame of preclinical research.

The paper describes the results of preclinical testing of the preparation "Vaccine allantoic split-virus inactivated against seasonal influenza." Acute toxicity and local irritating effect, anaphylactic reactions to different antigens (vaccine and ovalbumin), delayed-type hypersensitivity to ram erythrocytes, humoral immune response in hemaggtination reaction, immunogenic activity was studied in laboratory animals of various species (mice, rats, guinea pigs). Comparative analysis of the results from testing immunogenic activity of the preparation under study and the commercial influenza vaccines was performed. The preclinical testing has demonstrated safety and immune response of the seasonal split influenza vaccine, so it may be recommended for clinical study on limited contingent of volunteers.