Immunogenicity and safety of RAZI recombinant spike protein vaccine (RCP) as a booster dose after priming with BBIBP-CorV: a parallel two groups, randomized, double blind trial.

BACKGROUND: The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV). METHODS: We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions. RESULTS: We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths. CONCLUSIONS: BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

Effects of intranasal administration of violet oil in dry eye disease.

BACKGROUND: Dry eye disease is a disorder of the tear film. In this study, the effect of Viola odorata L. oily extract was examined for the treatment of patients suffering from dry eye disease. METHODS: A randomised, double-blind, placebo-controlled study was designed. During the trial, Schirmer's test, tear breakup time, Oxford staining and the Ocular Surface Disease Index were assessed. Overall, 105 patients with dry eye symptoms between the ages of 18 and 60 years were allocated to the violet-almond oil, almond oil and placebo (1% w/v hydroxypropyl methylcellulose solution) groups. The treatment and placebo were administered intranasally, two drops three times a day for one month. The patients were followed up for four weeks. A total of 91 patients (32, 29 and 30 in the violet-almond oil, almond oil and placebo groups, respectively) completed the study. RESULTS: At baseline, there was no difference between the three groups in terms of demographic data and the measurement parameters. After the intervention, the results revealed that the Schirmer's score without local anaesthesia and the tear breakup time results significantly improved in the violet-almond oil group. One-way ANOVA indicated a significant improvement in the Schirmer's score, tear breakup time and Ocular Surface Disease Index of the treatment group, as compared with the other groups (p < 0.05). However, the obtained results did not present any significant mean difference between and within the groups of the Oxford staining grade (p > 0.05). CONCLUSIONS: This trial showed that the intranasally administered V. odorata L. oily extract enhances tear production and improves tear film stability.

Synergistic co-delivery of doxorubicin and melittin using functionalized magnetic nanoparticles for cancer treatment: loading and in vitro release study by LC-MS/MS.

In this study, citric acid-functionalized Fe3O4 magnetic nanoparticles (CA-MNPs) were prepared via a coprecipitation method and were fully characterized. Doxorubicin (DOX) and melittin (MEL), as anticancer agents, were loaded onto CA-MNPs surface through electrostatic interactions with the aim to achieve an effective co-delivery system for cancer therapy. The loading efficiency and in vitro release profiles of DOX and MEL were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The MS/MS step was performed in the selected reaction monitoring (SRM) mode which enabled simultaneous quantification of the analytes with high specificity and sensitivity. An excellent loading efficiency of about 100% was achieved for DOX and MEL in a drug to nanocarrier ratio of 1:10. The in vitro release of the drugs from CA-MNPs was evaluated for 8 h at pH 7.4, 5.5 and 4.5. The experimental results revealed that the release behaviour of both of the anticancer agents was strongly pH-dependent and significantly enhanced at pH 4.5. The in vitro MTT assay on MCF-7 breast cancer cell line exhibited a synergistic effect between DOX and MEL which led to substantially greater antitumor efficacy, compared to single administration of these anticancer agents at equivalent doses. The results indicated that the co-delivery system of (DOX/MEL)-loaded CA-MNPs is highly capable to be used in magnetically targeted cancer therapy.