Current Approaches to Develop a Live Vaccine against Leishmania major

Leishmaniasis is an infectious disease that is endemic in 88 countries. Most of the patients after recovery from the infection develop a long-lived natural immunity against re-infection. Reactivation of leishmaniasis subsequent to suppression of the immune system due to HIV infection or administration of systemic immunosuppressive drugs, underscores the importance of developing new drugs and effective vaccine. Despite the many efforts that have been done, there is still no effective vaccine. Up to now, many candidate vaccines from three generations of the vaccine, including Live/killed vaccines, subunit vaccines, and DNA vaccines have been developed and studied. However the sophisticated vaccines, such as prime-boost DNA vaccines are introduced, the best results are obtained from live vaccines. As safety is the most important obstacle to the use of live vaccines, many different approaches have been used to enhance the safety of live vaccine candidates. In this short review, these approaches are summarized

The effect of fasting on the functioning of the immune system based on the measurement of plasma granulysin level

For downloading the full-text of this article please click here.Background and Objectives: Plasma granulysin levels as a biomarker of the immune system are currently being considered. NK cells are a major source of plasma granulysin. Plasma granulysin levels can reflect the total population of NK cell activity in the body. The effect of Ramadan fasting on the immune system function based on the measurement of plasma granulysin levels  have not been studied yet.Materials and Methods: A total of 44 male volunteers with a mean age of 41.15±13.6 years were selected for the study. Blood samples were obtained on the 29th days of fasting and also four month after Ramadan. Plasma Granulysin, triglyceride (TG), cholesterol (Chol), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), FBS, Uric acid and CRP were investigated.Results: It was observed that the mean concentrations of serum CRP on the 29th day of Ramadan were significantly lower than those recorded four months after Ramadan. Mean concentrations of serum LDL on the 29th day of Ramadan were significantly higher than those recorded four months after Ramadan. There was no difference between fasting and non-fasting groups in plasma granulysin levels.Conclusion: Fasting caused modulation in the CRP level, but did not affect plasma granulysin levels.Keywords:  Ramadan fasting; Granulysin; ImmunomodulationFor downloading the full-text of this article please click here

YKL-40 Gene Expression and Plasma Levels of CD30 are not Affected by Isoflurane or Propofol: Pilot Study

Background: It has been hypothesized that the body's response to anesthesia techniques can increase risk of cancer recurrence and metastatic disease after surgery and also can modulate immune responses. Some acute inflammatory markers have been measured to survey the immunomodulatory effect of anesthesia, but in this research, we studied the plasma level of CD30 and YKL-40 gene expression which can present major changes of the immune system.Materials and Methods: Our study was a controlled before and after study. 34 women with biopsy-proven breast cancer were randomized to receive either propofol general anesthesia (n=17) or standard isoflurane general anesthesia (n=17). There were no significant differences between the two patient groups in age, body weight, and height, length of general anesthesia, operative time and group of surgery. The blood samples were collected in two different sets, before anesthesia and 72-h postoperatively. Soluble CD30 (sCD30) plasma level was measured by ELISA and YKL-40/CHI3L1 gene expression was evaluated by real-time-PCR.Results: The results showed that the anesthetics, propofol and isoflurane, have no effect on the expression of YKL-40. Despite increased in the expression of YKL-40 that was observed in patients receiving isoflurane, this increase was not statistically significant. There was no significant increase or decrease in plasma concentrations of sCD30.Conclusion: YKL-40 and sCD30 are not affected by isoflurane or propofol.  So, in immunological perspective, there is no preference in use of isoflurane or propofol in breast cancer patients

اثرات تعدیل ایمنی روزه داری ماه رمضان بر میزان پلاسمایی گرانولایزین

Background and Objectives: Plasma granulysin levels as a biomarker of the immune system are currently being considered. NK cells are a major source of plasma granulysin. Plasma granulysin levels can reflect the total population of NK cell activity in the body. The effect of Ramadan fasting on the immune system function based on the measurement of plasma granulysin levels  have not been studied yet. Materials and Methods: A total of 44 male volunteers with a mean age of 41.15±13.6 years were selected for the study. Blood samples were obtained on the 29th days of fasting and also four month after Ramadan. Plasma Granulysin, triglyceride (TG), cholesterol (Chol), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), FBS, Uric acid and CRP were investigated. Results: It was observed that the mean concentrations of serum CRP on the 29th day of Ramadan were significantly lower than those recorded four months after Ramadan. Mean concentrations of serum LDL on the 29th day of Ramadan were significantly higher than those recorded four months after Ramadan. There was no difference between fasting and non-fasting groups in plasma granulysin levels. Conclusion: Fasting caused modulation in the CRP level, but did not affect plasma granulysin levels.سابقه و اهداف: میزان پلاسمایی گرانولایزین که می‌تواند بیومارکری باشد برای بیان وضعیت فعالیت سیستم ایمنی، در حال حاضر بسیار مورد توجه است. سلول‌هایNK ، منبع اصلی گرانولایزین پلاسما محسوب می‌شوند، بنابراین میزان پلاسمایی گرانولایزین می‌تواند انعکاسی از  فعالیت جمعیت کلی سلول‌های NK بدن باشد. تاکنون مطالعه‌یی در زمینه‌ی تأثیر روزه‌داری بر کارکرد سیستم ایمنی، بر مبنای اندازه‎‌گیری گرانولایزین پلاسمایی انجام نشده است. مواد و روش‌ها: در مجموع 44 داوطلب مرد با میانگین سنی 6/13 ± 15/41 سال برای مطالعه انتخاب شدند. در بیست و نهمین روز ماه رمضان و 4 ماه پس از ماه رمضان، خون‌گیری صورت گرفت و غلظت پلاسمایی گرانولایزین، CRP، تری گلیسرید، کلسترول، اسید اوریک و قند خون اندازه‌گیری شد. یافته‌ها: غلظت سرمی CRP پس از 29 روز روزه‌داری به‌طور قابل توجهی کم‌تر از مقدار آن در ماه چهارم پس از روزه‌داری بود. متوسط غلظت LDL در روز 29 روزه‌داری، بیش از ماه چهارم پس از روزه داری بود. تفاوتی در میانگین غلظت گرانولایزین در شرایط روزه‌داری در مقایسه با غیر روزه‌داری دیده نشد. نتیجه‌گیری: روزه‌داری تعدیل CRP را سبب می‌شود ولی بر سطح پلاسمایی گرانولایزین اثر ندارد.&nbsp

Downregulating the Expression of CHID1 by Chitin Microparticles Mixed Leukocyte Culture

Abstract Background: chitin and its derivates microparticles (MPs) have immunomodulatory activities. In this study, we examined the effect of size, purity and acetylation degree of chitin MPs on CHID1- encoding SI-CLP, involved in inflammation- gene expression in mixed leukocyte culture. Materials and Methods: Small (<40) and medium(40-70) sized chitin MPs were prepared by sonication, and they were used in treatment of leukocyte mixed culture in comparison with chitosan and also shrimp shell small-sized MPs. Neutral red uptake assay and microscopic examination of apoptosis were used to assess cytotoxicity of MPs. Finally, following cell treatment with MPs (100 μg/mL) for 48h, expression levels of CHID1 gene were determined by Real Time PCR. Results: Different concentrations of chitinous MPs hadn’t any cytotoxic effects. In gene expression analysis, small-sized chitin MPs (<40 µ) resulted in down regulation of CHID1 gene expression (p=0.004), while other MPs didn’t change it significantly. Conclusion: Size, purity and acetylation degree of chitin MPs influence their interference in immune cells interactions and it seems small-sized chitin MPs can potentially modulate immune responses through decreasing CHID1 gene expression. Using small-sized chitin MPs may be effective to treat allergies which their treatment strategies rely on modulating the immune responses

Immune Responses Elevation by Intranasal Administration of Chitosan Microparticles Adjuvanted Poly-Epitope against Streptococcus pneumoniae in BALB/c Mice: Immune responses elevation against S. pneumoniae mice

Background: Designing inhaled vaccine formulations against respiratory pathogens like Streptococcuspneumoniae (S. pneumoniae) lead to more effective mucosal and local immunity in the upper respiratory tract.Choosing chitosan (the chitin de-acetylated derivative) as a biocompatible, biodegradable, and non-toxicbiopolymer and a suitable mucosal adjuvant can help to stimulate both systemic cellular and humoral immunity,as well as local protection, is valuable. The purpose of this study is the determination the ability of the designedpneumococcal immunogenic polytope to evoke a bactericidal response when adjuvanted with chitosanmicroparticles.Materials and Methods: We chose virulence proteins from S. pneumoniae (Pneumolysin, Neuraminidase, ZinkMetalloproteinase, Hydrolase) and designed a new multi-epitope construct by linking their individual predictedT and B cell epitopes. Intranasal immunization with PNEU protein and chitosan microparticle administered inBALB/c mice.Results: Our formulation showed enhanced systemic IgG-2a, IgA, and mucosal IgA antibody concentrations,revealing significant humoral responses to the polytope. The polytope increases the number of IFN-γ-producing cells in the re-stimulation of splenocytes in the culture medium and a rise in the concentrations ofIL-6, IL-17, and TNF-α along with the regulatory responses of IL-10 presented the capacity of the formulationto provoke immune responses. The bactericidal test ultimately confirmed the high efficacy of the vaccine ininhibiting the bacteria.Conclusion: Immunological responses were significantly induced after intranasal administration of the S.pneumoniae computational predicted polytope accompanied by chitosan microparticles as a potent mucosaladjuvant. Bactericidal assay confirmed effective immune responses in S. pneumoniae inhibition

Designing and Expression of an Immunogenic Poly-Epitope Protein from Streptococcus pneumoniae: An immunogenic protein from S. pneumoniae

A well-designed vaccine against Streptococcus pneumonia, a respiratory pathogen, by immunoinformatics approaches can lead to an effective mucosal and local immunity in the upper respiratory tract. In this study, we chose virulence proteins from different strains of S. pneumonia (Pneumolysin, Neuraminidase, Zink-Metalloproteinase, and Hydrolase) and designed a new multi-epitope construct by properly linking the individual predicted T and B cell specific epitopes. Then, the polytope, named PNEU, was expressed in Escherichia coli as a prokaryotic system. Through computational calculations, PNEU polypeptide with 216 aa has the theoretical pI 8.04 and instability index 33.63, which show that it is a stable and soluble protein. Also, the 3D structure of PNEU was predicted by Phyre2 server with 96.0% confidence. In conclusion, PNEU protein can be considered as a stable and soluble immunogenic protein, which may be efficiently used for immunity stimulation in laboratory animals, investigated in future studies. Highlights The poly epitope PNEU protein is a vaccine candidate for Streptococcus pneumonia. PNEU is a stable and soluble protein. PNEU shows a proper folding through in silico 3D structure prediction. PNEU protein expression in prokaryotic systems was confirmed. &nbsp