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.

Safety and efficacy of the FAKHRAVAC compared with BBIBP-Corv2 against SARS-CoV-2 in adults: a non-inferiority multi-center trial.

BACKGROUND: We compared Fakhravac and BBIBP-Corv2 vaccines in a phase III trial. METHOD: We conducted a multicenter, parallel-group, active-control, non-inferiority clinical trial with pragmatic considerations assessing the safety and efficacy of Fakhravac and BBIBP-Corv2 vaccines. We started with two randomized double-blind arms and added two non-randomized open-label arms (based on participant preference) because of slow recruitment. The adult population received 0.5 ml (10 µg per dose) intramuscular injections of Fakhravac or BBIBP-Corv-2 vaccines 21 days apart. The primary outcome was the occurrence of PCR-positive symptomatic Covid-19 disease 14 days or more after the second injection. A 10% non-inferiority margin to the reported 72.8% efficacy of BBIBP-Corv2 was assumed. Cox proportional hazard modeling was used to estimate hazard ratios and their 95% confidence intervals. RESULT: We enrolled 24,056 adults in four groups (randomized-Fakhravac: 824, randomized-BBIBP-Corv2: 832; Non-randomized-Fakhravac: 19,429, Non-randomized-BBIBP-Corv2: 2971). All observed local and systemic adverse reactions were generally self-limited and resolved completely. We observed similar Serious Adverse Event (SAE) rates in the BBIBP-Corv2 (2.57, 95% CI 1.33-4.49) and Fakhravac (2.25, 95% CI 1.72-2.89) groups; none of which were related to the vaccines received. We recorded 9815 Medically Attendant Adverse Events (MAAE), 736 of which were categorized as somehow related. The rate of related MAAE in the Fakhravac was similar to the BBIBP-Corv2 groups (0.31 and 0.26 per 1000 person-day) in the randomized and considerably higher (0.24 and 0.07 per 1000 person-day) in the non-randomized arms. We observed 129 (35% of the 365 required by target sample size) events of PCR + symptomatic Covid-19 during four months of active follow-up in the randomized arm, demonstrating that those receiving the Fakhravac vaccine were significantly less likely (HR = 0.69; 95% CI 0.49-0.98) to be diagnosed with PCR + symptomatic Covid-19 compared with those receiving BBIBP-Corv2 vaccine. After adjusting for type I error using the O'Brien Fleming method, the Fakhravac vaccine was non-inferior to the BBIBP-Corv2 (assuming a 10% non-inferiority margin to the reported 72.8% BBIBP-Corv2 vaccine efficacy; HR < 1.35) (One-way test: HR = 0.66; 99.8% CI 0.38-1.15). In the non-randomized arm, the results were inconclusive (HR = 1.23; 95% CI 0.96-1.61). We observed 5 cases of hospitalized Covid-19 in the randomized arm, none of which occurred in the Fakhravac vaccine group. Those receiving the Fakhravac vaccine were four times less likely to go to the hospital because of a Covid-19 diagnosis (HR = 0.24; 95% CI 0.10-0.60). The vaccine efficacy of the Fakhravac vaccine is estimated to be 81.5% (95% CI 81-82.4%). CONCLUSION: Fakhravac inactivated SARS-CoV-2 vaccine has comparable safety and efficacy to the BBIBP-Corv2 vaccine. Trial registration This study was registered with the Iranian Registry of Clinical Trials ( www.irct.ir : IRCT20210206050259N3).

Geographic distribution and time trends of water-pipe use among Iranian youth and teenage students: A meta-analysis and systematic review.

Water-pipe tobacco smoking is harmful to health, yet its rate of prevalence remains uncertain. Recent evidence has shown that the prevalence of water-pipe smoking among students is higher than in the general population. In this study, a systematic review of related literature on water-pipe use was conducted, and for this purpose, 76 articles were examined in the study. In this vein, geographic distribution and time trends of water-pipe consumption in Iran were considered. The results of this study showed that lifetime, last-year, and last-month prevalence of water-pipe smoking use among Iranian students were 28.78 (25.07-32.49), 20.84 (16.01-25.66), and 16.36 (11.86-20.85), respectively. The results also showed a wide variation by the region and sex in Iran. This study has shown the importance of addressing public prevention and alerting programs in schools and universities.

Cardio-metabolic and socio-demographic risk factors associated with dependency in basic and instrumental activities of daily living among older Iranian adults: Bushehr elderly health program.

BACKGROUND: Iran's population is aging. Disability is a major public health problem for older adults, not only in Iran but all over the world. The purpose of this study was to investigate the relationship between cardio-metabolic and socio-demographic risk factors and disability in people 60 years and older in Iran. METHODS: The baseline (cross-sectional) data of 2426 samples from the Bushehr Elderly Health (BEH) program was included in the analysis. The participants were selected through multi-stage random sampling in Bushehr, southern Iran. Socio-demographic characteristics, as well as the history of diabetes and other chronic diseases, and smoking were measured using standardized questionnaires. Anthropometric measurements and laboratory tests were performed under standard conditions. Dependency was determined by the questionnaires of basic activities of daily living (BADL) and instrumental activities of daily living (IADL) using Barthel and Lawton scales respectively. Multiple logistic regression was used in the analysis. RESULTS: Mean (Standard Deviation) of the participants' age was 69.3 (6.4) years (range: 60 and 96 years), and 48.1% of the participants were men. After adjusting for potential confounders, being older, being female (OR (95%CI): 2.3 (1.9-2.9)), having a lower education level, a history of diabetes mellitus (OR: 1.4 (1.2-1.7)) and past smoking (OR: 1.3 (1.0-1.6)), and no physical activity (OR: 1.5 (1.2-1.9)) were significantly associated with dependency in IADL. Also, being older and female (OR: 2.4 (1.9-3.0)), having a lower education level, no physical activity (OR: 2.2 (1.6-2.9)) and daily intake of calories (OR: 0.99 (0.99-0.99)) were associated with dependency in BADL. CONCLUSION: Dependency in older adults can be prevented by increasing community literacy, improving physical activity, preventing and controlling diabetes mellitus, avoiding smoking, and reducing daily calorie intake.