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Botulinum neurotoxins (BoNTs) are the most potent toxins on Earth and are classified as Category A biological agents. BoNTs lead to paralysis in humans and cause botulism. Antibody therapeutics can effectively treat toxin-mediated infectious diseases. In this study, we generated a pharmaceutical humanized monoclonal antibody (HZ45 mAb) to prevent or treat botulism. HZ45 binds to the heavy chain receptor (HCR) domain of the toxin, preventing the toxin from entering the cell. The mAb was produced using hybridoma technology and phage display. We evaluated HZ45 mAb for the neutralization of BoNT serotype A (BoNT/A) in mice and rabbits. The survival results showed that pretreatment with HZ45 mAb provided 100% protection at a dose of 0.1 mg per mouse against a maximum of 100 LD50 of BoNT/A. To assess the therapeutic efficacy of HZ45 mAb in New Zealand white rabbits (NZWs), a 5 mg dose was administered 4 or 8 h after challenge with 10 LD50. The results indicated that 5 mg of HZ45 could treat the NZWs within 8 h after exposure to 10 LD50 botulinum. Consequently, in an in vivo context, including mice and rabbits, HZ45 mAb could protect against botulinum type A intoxication.

Potential threat of smallpox bioterrorism and concerns related to the adverse effects of currently licensed live-virus vaccines suggest the need to develop novel vaccines with better efficacy against smallpox. Use of DNA vaccines containing specific antigen-encoding plasmids prevents the risks associated with live-virus vaccines, offering a promising alternative to conventional smallpox vaccines. In this study, we investigated the efficiency of toll-like receptor (TLR) ligands in enhancing the immunogenicity of smallpox DNA vaccines. BALB/c mice were immunized with a DNA vaccine encoding the vaccinia virus L1R protein, along with the cytosine–phosphate–guanine (CpG) motif as a vaccine adjuvant, and their immune response was analyzed. Administration of B-type CpG oligodeoxynucleotides (ODNs) as TLR9 ligands 24 h after DNA vaccination enhanced the Th2-biased L1R-specific antibody immunity in mice. Moreover, B-type CpG ODNs improved the protective effects of the DNA vaccine against the lethal Orthopoxvirus challenge. Therefore, use of L1R DNA vaccines with CpG ODNs as adjuvants is a promising approach to achieve effective immunogenicity against smallpox infection.

A small interfering RNA (siRNA) inhibitors have demonstrated the novel modality for suppressing infectious diseases. Sixty-one siRNA molecules, predicted by the bioinformatics programs, were screened for the possibility of treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in vitro plaque assay. Among six siRNA leads with the efficacy of reducing plaque number, the siRNA targeting RNA-dependent RNA polymerase (RdRp) showed a reduction in SARS-CoV-2 infection-induced fever and virus titer in the Golden Syrian hamster and rhesus macaque. These results suggest the potential for RdRp targeting siRNA as a new treatment for the coronavirus disease 2019 (COVID-19). Competing Interest Statement The authors have declared no competing interest.

Introduction Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. Objective We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017–31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. Methods Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. Results In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55–0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28–8.12]). Conclusions We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.