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.

Mortality rate of people exposed to Mustard Gas during Iran-Iraq war in Sardasht, Iran: a 32 years retrospective cohort study.

BACKGROUND: Mustard gas (MG) is one of the most widely used chemical weapons in the past century. However, little information exists concerning long-term mortality from MG exposure. In this study, we investigated mortality rate among civilian people exposed to MG during Iran-Iraq war in Sardasht in Iran after 32 years.  METHODS: In this retrospective cohort study, data of people exposed to MG in Sardasht in 1987 were extracted from the Veterans and Martyr Affair Foundation of Iran up to March 20, 2019. Mortality rate, cumulative mortality and standardized mortality ratio with 95% confidence interval were calculated to explain mortality in the cohort, and then compared with general Iranian population. Cox regression analysis was used to indicate factor affecting the risk of death in the cohort.  RESULTS: Out of 1,203 exposed people at the beginning of the period, 148 people died by the end of the study, with an average age of 66.42 at the time of death. Total person-years of the people up to end of the study were 38,198.63 and mortality rate was equal to 387 per 100,000 persons-years. Total number of observed deaths was less than expected death and the all-cause standardized mortality ratio (SMR) was determined as 0.680 (95% CI: 0.574 - 0.798). Cause-specific SMR showed that observed death due to respiratory diseases was higher than expected (SMR: 1.75) (95% CI: 1.145 - 2.569). The results of univariate and multivariate cox regression analysis showed that increasing age and having severe late complications in lung were associated with increased risk of death among people in the cohort. CONCLUSION: In general, this result indicated that acute exposure to MG, even without wearing protective clothing and masks, could not increase all-cause mortality after 32 years if accompanied by special and ongoing care for those exposed.