Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial.

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Safety and Efficacy of Combined Intramuscular/Intranasal RAZI-COV PARS Vaccine Candidate Against SARS-CoV-2: A Preclinical Study in Several Animal Models.

Several vaccine candidates for COVID-19 have been developed, and few vaccines received emergency approval with an acceptable level of efficacy and safety. We herein report the development of the first recombinant protein-based vaccine in Iran based on the recombinant SARS-CoV-2 spike protein in its monomeric (encompassing amino acid 1-674 for S1 and 685-1211 for S2 subunits) and trimer form (S-Trimer) formulated in the oil-in-water adjuvant system RAS-01 (Razi Adjuvant System-01). The safety and immunity of the candidate vaccine, referred to as RAZI-COV PARS, were evaluated in Syrian hamster, BALB/c mice, Pirbright guinea pig, and New Zeeland white (NZW) rabbit. All vaccinated animals received two intramuscular (IM) and one intranasal (IN) candidate vaccine at 3-week intervals (days 0, 21, and 51). The challenge study was performed intranasally with 5×106 pfu of SARS-CoV-2 35 days post-vaccination. None of the vaccinated mice, hamsters, guinea pigs, or rabbits showed any changes in general clinical observations; body weight and food intake, clinical indicators, hematology examination, blood chemistry, and pathological examination of vital organs. Safety of vaccine after the administration of single and repeated dose was also established. Three different doses of candidate vaccine stimulated remarkable titers of neutralizing antibodies, S1, Receptor-Binding Domain (RBD), and N-terminal domain (NTD) specific IgG antibodies as well as IgA antibodies compared to placebo and control groups (P<0.01). Middle and high doses of RAZI-COV PARS vaccine significantly induced a robust and quick immune response from the third-week post-immunization. Histopathological studies on vaccinated hamsters showed that the challenge with SARS-CoV-2 did not induce any modifications in the lungs. The protection of the hamster was documented by the absence of lung pathology, the decreased virus load in the lung, rapid clearance of the virus from the lung, and strong humoral and cellular immune response. These findings confirm the immunogenicity and efficacy of the RAZI-COV PARS vaccine. Of the three tested vaccine regimens, the middle dose of the vaccine showed the best protective immune parameters. This vaccine with heterologous prime-boost vaccination method can be a good candidate to control the viral infection and its spread by stimulating central and mucosal immunity.

Shirazi thyme (Zataria multiflora) extract can alleviate allergic rhinitis: a randomized clinical trial.

INTRODUCTION: Atopic diseases are global concerns in the today's industrialized world. Allergic rhinitis is the most common allergic condition affecting 20% of individuals. This disorder is associated with remarkable morbidity and rising healthcare expenditure. AIM: Considering the anti-inflammatory properties of a plant Zataria multiflora (ZM) with the common name of Shirazi thyme, a randomized clinical trial was designed to evaluate the alleviation of the symptoms of allergic rhinitis. MATERIAL AND METHODS: A total of 30 allergic rhinitis patients were randomly and equally assigned to experimental and control groups. Afterwards, the case group was treated with an extract of ZM and the control group with placebo for 2 months. Finally, the clinical signs and symptoms before and after the treatment according to the SNOT22 questionnaire were analysed. RESULTS: Comparing the symptoms of allergic rhinitis and an average score of SNOT22 questionnaire between the two groups before the intervention provided some difference, which was significantly greater after the treatment. Based on this questionnaire, our patients in the ZM syrup group had lower grades than before the treatment and experienced amelioration. CONCLUSIONS: Regarding the significant effect of the ZM syrup in reducing symptoms of allergic rhinitis, its use is highly recommended. Since allergic rhinitis is a multifactorial condition, the use of herbal antioxidants along with conventional treatment would result in a more effective improvement of the disease.

Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker.

SARS-CoV-2 infections cause the current coronavirus disease (COVID-19) pandemic and challenge the immune system with ongoing inflammation. Several redox-relevant micronutrients are known to contribute to an adequate immune response, including the essential trace elements zinc (Zn) and selenium (Se). In this study, we tested the hypothesis that COVID-19 patients are characterised by Zn deficiency and that Zn status provides prognostic information. Serum Zn was determined in serum samples (n = 171) collected consecutively from patients surviving COVID-19 (n = 29) or non-survivors (n = 6). Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study were used for comparison. Zn concentrations in patient samples were low as compared to healthy subjects (mean ± SD; 717.4 ± 246.2 vs 975.7 ± 294.0 µg/L, P < 0.0001). The majority of serum samples collected at different time points from the non-survivors (25/34, i.e., 73.5%) and almost half of the samples collected from the survivors (56/137, i.e., 40.9%) were below the threshold for Zn deficiency, i.e., below 638.7 µg/L (the 2.5th percentile in the EPIC cohort). In view that the Se status biomarker and Se transporter selenoprotein P (SELENOP) is also particularly low in COVID-19, we tested the prevalence of a combined deficit, i.e., serum Zn below 638.7 µg/L and serum SELENOP below 2.56 mg/L. This combined deficit was observed in 0.15% of samples in the EPIC cohort of healthy subjects, in 19.7% of the samples collected from the surviving COVID-19 patients and in 50.0% of samples from the non-survivors. Accordingly, the composite biomarker (SELENOP and Zn with age) proved as a reliable indicator of survival in COVID-19 by receiver operating characteristic (ROC) curve analysis, yielding an area under the curve (AUC) of 94.42%. We conclude that Zn and SELENOP status within the reference ranges indicate high survival odds in COVID-19, and assume that correcting a diagnostically proven deficit in Se and/or Zn by a personalised supplementation may support convalescence.

A Biographical History of Some Iranian Pioneers in Medical Immunology and Allergy.

The oldest literature that mentioned the immunity was related to the plague of Athens in 430 BC. The germ theory had more influence on the description of the discrimination between self and non-self which is the core concept of immunology. Allergic diseases were known from 2,000 years ago while Rhazes wrote the first medical monograph about seasonal allergic rhinitis. In Iran, Dr. Mohammad Kermanshahi introduced the basic concepts of serology in 1900. The first Department of Serology was established at Tehran University, Faculty of Medicine in 1951 by Prof. Dr. Hassan Mirdamadi. After that, immunology entered into the cellular and molecular period. Prof. Mohammad Ali Maleki established the first Iranian Society of Allergy and then Prof. Abolhassan Farhoodi found the first Department of Clinical Immunology and Allergy at Tehran University. In this paper, we review the role of famous Iranian scientists and physicians in the progress of modern immunology and allergy from a historical perspective.

Oral Administration of Zataria multiflora Extract Decreases IL-17 Expression in Perennial Allergic Rhinitis.

BACKGROUND: Rhinitis, which occurs most commonly as allergic rhinitis and affects 20% of the world's population, is a major health care burden causing significant morbidity. Considering the high prevalence of allergic rhinitis and anti-inflammatory effects of thyme, a favorite condiment, we performed a randomized clinical trial to determine whether thyme can relieve allergic rhinitis symptoms and affect the expression of TH17- and T-regulatory cell- (Treg) related cytokines IL-17, TGF-ß, FOXP3, and IL-10. METHODS: Thirty patients with allergic rhinitis symptoms and positive skin prick test for common aero allergens were randomly assigned to experimental or control groups. The experimental group received thyme or Zataria multiflora (ZM) extracts and the control group received placebo for two months. Expression of IL-17, TGF-ß, FOXP3, and IL-10 was evaluated in all subjects by real-time PCR before and after intervention. RESULTS: After treatment IL-17 expression was significantly less in the ZM group than in controls (p<0.05), while TGF-ß, FOXP3, and IL-10, expression were not significantly changed. CONCLUSION: Given the significant effect of thyme in reducing symptoms of allergic rhinitis and decrease IL-17 gene expression and because allergic rhinitis is a multifactorial disease, the administration of thyme extract along with conventional treatments may benefit allergic rhinitis sufferers.

Serum Levels of TNF-, IL-6, and Selenium in Patients with Acute and Chronic Coronary Artery Disease.

BACKGROUND: Selenium (Se) is part of the glutathione peroxidase enzyme complex (GSH-PX) that plays an important role in antioxidant mechanisms in body, also it has been demonstrated that populations with low Se intake have 2-3 times greater risk of ischemic heart disease. OBJECTIVE: To determine the circulating levels of IL- 6, TNF-alpha, Cu, Zn, and Se in patients with chronic coronary artery disease (CCAD), acute myocardial infarction (AMI), and normal individuals. METHODS: Patients were divided into two groups: 25 subjects with CCAD and 25 patients with AMI. The control group included 50 normal individuals who did not have any history of ischemic heart disease, and were sex and age matched with the patients. Blood samples were collected during the first hours after the onset of chest pain in AMI group. Serum concentration of Se, Cu, and Zn were determined by atomic absorption spectrometry and TNF-alpha and IL-6 levels were measured using ELISA method. RESULTS: In both groups of patients there was a significant reduction in serum Se levels (82.36 + 11.31 g/L in CCAD, 74.08+11.31g/L in AMI, and 105+32.52g/L in the control group, p=0.03). TNF-alpha titers were increased in AMI patients compared with CCAD and control group. Mean TNF-alpha levels were 37.44 pg/ml in CCAD, 914.32 pg/ml in AMI, and 4.80 pg/ml in the control group (p=0.01). Serum levels of IL-6 in CCAD and AMI patients were 3.28 15.55 pg/ml and 472207.88 pg/ml, respectively, and 1.28 pg/ml in the control group (p=0.001). CONCLUSION: These findings confirm previous studies and demonstrate that patients suffering from AMI exhibit lower plasma concentrations of Se and higher concentrations of pro-inflammatory cytokines of TNF-alpha and IL-6.