Immunogenicity and safety evaluation of a newly manufactured recombinant Baculovirus-Expressed quadrivalent influenza vaccine in adults 18 years old and Above: An Open-Label, phase III extension study.

In the face of global health threats, there is a growing demand for vaccines that can be manufactured on a large scale within compressed timeline. This study responds to this imperative by delving into the evaluation of FluGuard, a novel recombinant influenza vaccine developed by Nivad Pharmed Salamat Company in Iran. Positioned as a phase 3 extension, the research aimed to evaluate the safety and immunogenicity of FluGuard in volunteers aged 18 and above. The study was conducted as a single-center, open-label clinical trial. All eligible volunteers received FluGuard (2021-2022 Formula) on day 0. Safety assessments occurred at days 1, 4, 7, 14, 28 and 42 post-vaccination. Immunogenicity was measured through seroconversion, seroprotection, and geometric mean titer fold increase in subgroups of 250 volunteers. Among the 4,260 volunteers were screened and assessed for eligibility, 1000 were enrolled. At day 28 post-vaccination, seroconversion rates for A/H1N1, A/H3N2, B/Yamagata, B/Victoria were 53.4 % [95 %CI: 46.7-60], 57.7 % [95 %CI: 51.1-64.3], 54.3 % [95 %CI: 47.7-60.9], and 36.2 % [95 %CI: 29.8-42.6], respectively in volunteers 18 years and above. The most common solicited adverse events were pain at the injection site, malaise, and headache. No suspected unexpected adverse events and adverse events of special interest occurred during the study period. Our findings suggested that FluGuard® exhibits a desirable safety profile and provides sufficient immunogenicity against influenza virus types A and B. However, extended studies are warranted to assess the long-term protective efficacy. Trial Registration: The study protocol was accepted by Iranian registry of clinical trial; https://www.irct.ir; IRCT20201104049265N2.

Evaluation of the safety and efficacy of a biosimilar abobotulinum toxin type A in treating moderate-to-severe glabellar lines: A non-inferiority double blinded randomized controlled trial.

BACKGROUND: Injection of botulinum toxin for cosmetic purposes is a well-established practice. OBJECTIVES: This study was conducted to compare the safety and efficacy of Dyston® (investigational biosimilar abobotulinumtoxinA) with Dysport® (abobotulinumtoxinA, Ipsen) in the treatment of moderate-to-severe glabellar lines. METHODS: Out of 193 screened subjects, 126 volunteers with moderate-to-severe glabellar lines fulfilling eligibility criteria were randomized in a 1:1 ratio to receive either an intramuscular injection of 40-60 units of Dyston® or Dysport® . The primary objective was to test the non-inferiority of Dyston® compared with Dysport® as measured by the percentage of volunteers who achieved no or mild glabellar lines at maximum frown assessed by the physicians based on the Glabellar Line Severity Score (GLSS) at Day 30. Secondary endpoints included the improvement in the glabellar lines at maximum frown and rest states at Days 14, 60, 90, and 120 as well as the side effects of the treatment. RESULTS: Response rates at maximum frown were 75.44% (43/57) in the Dyston® group and 76.67% (46/60) in the Dysport® group on Day 30 (p value: 0.88, 95% CI: -14.24 to 16.70, diff: 1.23) as per-protocol set, and were 75.81% (47/62) and 76.19 (48/63) (p value: 0.96, 95% CI: -14.59 to 15.35, diff: 0.3) in the Dyston® and the Dysport® groups, respectively, based on modified intention to treat population. Adverse events were similar in both groups and mostly mild and well-tolerated. CONCLUSION: Treatment of moderate-to-severe glabellar lines with Dyston® was effective, tolerable, and non-inferior compared with Dysport® .

Immunogenicity and safety of a bivalent, adjuvant system 04-adjuvanted human papillomavirus vaccine in healthy female volunteers aged 15-25: a randomized, double-blind, phase III, noninferiority clinical trial.

OBJECTIVE: Vaccination is proven to significantly reduce the risk of human papillomavirus (HPV)-related complications, especially cervical cancer. This study aimed to assess the immunogenicity and safety of the investigational bivalent HPV vaccine (16/18), named Papilloguard (Noyan Pajouhan Biopharma, Tehran, Iran), in comparison with the reference product (Cervarix, bivalent HPV vaccine (16/18) manufactured by GlaxoSmithKline, Rixensart, Belgium) in a three-dose regimen. METHODS: This trial was a randomized, controlled, double-blind, phase III study of two HPV vaccines in healthy female volunteers aged 15-25. The primary endpoint was to test the noninferiority of Papilloguard (Noyan Pajouhan Biopharma) to Cervarix (GlaxoSmithKline) as measured by the geometric mean titer (GMT) ratios of HPV-16 and HPV-18 7 months after the first vaccination. Secondary endpoints were the proportion of local and systemic solicited and unsolicited events, and the number of females with seroconversion against HPV-16 and HPV-18 7 months after the first vaccination. RESULTS: Out of 504 screened women, 218 were enrolled. Seven months after the first vaccination, GMT ratios of HPV-16 and HPV-18 were 0.59 and 0.93, respectively. The seroconversion rates of both Papilloguard (Noyan Pajouhan Biopharma) and Cervarix (GlaxoSmithKline) were more than 96%. Both vaccinated groups had a generally good profile of solicited and unsolicited adverse events (AEs). The most common AE was discomfort at the injection site, which was well tolerated. CONCLUSION: The result analysis of this study supports the noninferiority of Papilloguard (Noyan Pajouhan Biopharma) to Cervarix (GlaxoSmithKline) in terms of safety and immunogenicity based on the GMT ratio. However, long-term comparative studies to evaluate the sustainability of GMT response and risk of cervical intraepithelial neoplasia grades 2-3 are needed.

Effect of heat treatment on the structure and stability of Grass pea (Lathyrus sativus) protein isolate/Alyssum homolocarpum seed gum nanoparticles.

In the present study, Grass pea protein isolate (GPPI)- Alyssum homolocarpum seed gum (AHSG) complex nanoparticles were formed through two fabrication methods and their physicochemical properties, structure and stability against sodium chloride and different pHs were investigated. Type 1 particles were formed by creating GPPI nanoparticles, and then coating them with AHSG; while Type 2 particles were fabricated through the heat treatment of GPPI-AHSG complexes at 85 °C for 15 min. The preparation methods did not influence the magnitude of electrical charges on biopolymer particles. The particle size analysis revealed that Type 2 particles had lower mean diameter (d = 360.20 nm) compared to Type 1 particles (d = 463.22 nm). Structural properties of Type 1 and Type 2 particles were determined using Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), Differential scanning calorimetry (DSC), Atomic force microscopy (AFM), and transmission electron microscopy (TEM). Hydrogen bonding, electrostatic and hydrophobic interactions were the main driving forces contributed to the formation of both GPPI-AHSG complex particles. Assessments of morphological and structural properties also indicated that both Type 1 and 2 particles had spherical shapes and heat treatment increased the ordered intermolecular structures in biopolymer particles. Type 2 particles had higher denaturation temperature and better pH and salt stability when compared to Type 1 particles. These results indicate that thermal treatment was effective for the fabrication of stable GPPI-AHSG complex nanoparticles.

Progressive collapse potential of different types of irregular buildings located in diverse seismic sites.

This paper evaluates the effects of severity of Torsional Irregularity (TI) and In-plane Discontinuity in Vertical Lateral force-resisting element Irregularity (IDVLI) together with seismic strength of the building on the progressive collapse potential of steel Special Moment-Resisting Frames (steel SMRFs), which were designed based on common seismic codes. In order to investigate the progressive collapse potential according to GSA 2013 guidelines, an interior or exterior column is removed in 3D modeled building using nonlinear dynamic analysis. Various TIs by defining the ratio of maximum relative lateral displacement of the story to average relative lateral displacement of the story between 1 to 1.6 and IDVLIs by disconnecting one or two columns in the first and second stories are selected. Buildings are 3, 6 and 9 stories high, and Los Angeles, California andGeorgia sites with high, moderate and low levels of seismicity, respectively, are considered. All corresponding buildings have similar seismic mass and are designed for approximately equal values of earthquake base shear, so the comparison process can be possible due to the comparison of equivalent-designed buildings. Gravity and seismic loads of buildings are applied based on ASCE 7-05, and steel design is carried out based on AISC 2010. The results show that buildings designed with greater TI have greater resistance to the progressive collapse phenomenon. Furthermore, buildings in a site with higher seismicity level have less progressive collapse potential. In IDVLI, the buildings located in a site with low seismicity are always rejected against progressive failure based on GSA 2013, whereas buildings located in a site with high seismicity are always acceptable. In addition, in a system with IDVLI, the scenario of external column removal always creates more critical conditions. Results toward the combined effects of irregularity and seismicity level of sites are presented.

Effect of decapitation and exogenous application of gibberellic acid (GA3) and cytokinin (CK) on some physiological characteristics of stevia.

Stevia (Stevia rebaudiana B.) has auxiliary buds that often remain dormant for a long time and sometimes remain dormant until the plants change at the reproductive stage. This study was designed out to investigate whether decapitation and exogenous application of plant growth regulators enhance the productivity of stevia through breaking the apical dominance and increasing physiological characteristics. Experiment was carried out as a factorial in randomized complete block design with three replications. Factors were consisted two agricultural practices (Decapitation and No-decapitation) and eight foliar spray including without spray as control, water spray, GA3 (300, 600 and 900 µm) and CK (100, 200 and 400 µm). The results of the present investigation indicated a positive response on number of branches and leaves, leaves and stem fresh weight and total dry weight, in both harvests not only from the decapitation of apical buds but also from foliar application of CK (400 µM). Thus, it can be concluded that the decapitation practices in conjunction with foliar application of CK (400 µM) could be used to increase the dry-leaf yield of stevia. However, further studies are required to standardize the dose of CK (400 µM) to improve the yield and quality of stevia.

Effect of waterlogging at different growth stages on some morphological traits of wheat varieties.

Excess rainfalls may be the cause of waterlogging in soil, which affects the growth and development of wheat. Therefore, the objectives of this study were to examine the effects of waterlogging on shoot and root growth and physiological characteristics of wheat. Three experiments were conducted: experiment 1 (E1): evaluation of seedling growth on ten Iranian winter wheat varieties with waterlogging periods (1-4, 4-8, 8-12, and 12-16 days starting from seed germination). Seminal roots and plumule were investigated at seedling. The others are E2: pretreatment of waterlogging (15 days) at tillering and stem elongation stages and its effects on shoot and root growth at anthesis stage and experiment 3 (E3): pretreatment of waterlogging (15 days) at tillering and jointing stages and its effects on yield and yield components and also evaluation of stress tolerance indexes. The results of the seedling growth test (E1) showed that 1-4- and 4-8-day waterlogging severity reduced seminal root length (94.5 to 93.7 %) and plumule length (86.2 to 50.0 %) compared to control. Results of E2 indicated that waterlogging stress decreased shoot dry weight, root dry weight, total secondary root length, and chlorophyll a + b content of flag leaf by 28-31, 44-35, 20-31, and 28-35 %, respectively. Also, result of E3 showed that the grain yields of wheat varieties at two conditions of stress were different in base tolerance indexes. In general, the responses of wheat varieties to waterlogging were different at the three experiments. The varieties that had the most of dry weight and length of the root were tolerant. Thus, it is possible to use these characteristics as an index for selecting the varieties with tolerance to waterlogging.