ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic is still ongoing. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) are circulating worldwide, making it resistant to existing vaccines and antiviral drugs. Therefore, the evaluation of variant-based expanded spectrum vaccines to optimize the immune response and provide broad protectiveness is very important. In this study, we expressed spike trimer protein (S-TM) based on the Beta variant in a GMP-grade workshop using CHO cells. Mice were immunized twice with S-TM protein combined with aluminum hydroxide (Al) and CpG Oligonucleotides (CpG) adjuvant to evaluate its safety and efficacy. BALB/c immunized with S-TM + Al + CpG induced high neutralizing antibody titers against the Wuhan-Hu-1 strain (wild-type, WT), the Beta and Delta variants, and even the Omicron variant. In addition, compared with the S-TM + Al group, the S-TM + Al + CpG group effectively induced a stronger Th1-biased cell immune response in mice. Furthermore, after the second immunization, H11-K18 hACE2 mice were well protected from challenge with the SARS-CoV-2 Beta strain, with a 100% survival rate. The virus load and pathological lesions in the lungs were significantly reduced, and no virus was detected in mouse brain tissue. Our vaccine candidate is practical and effective for current SARS-CoV-2 VOCs, which will support its further clinical development for potential sequential immune and primary immunization. IMPORTANCE Continuous emergence of adaptive mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the use and development of existing vaccines and drugs. The value of variant-based vaccines that are capable of inducing a higher and broader protection immune response against SARS-CoV-2 variants is currently being evaluated. This article shows that a recombinant prefusion spike protein based on a Beta variant was highly immunogenic and could induced a stronger Th1-biased cell immune response in mice and was effectively protective against challenge with the SARS-CoV-2 Beta variant. Importantly, this Beta-based SARS-CoV-2 vaccine could also offer a robust humoral immune response with effectively broad neutralization ability against the wild type and different variants of concern (VOCs): the Beta, Delta, and Omicron BA.1 variants. To date, the vaccine described here has been produced in a pilot scale (200L), and the development, filling process, and toxicological safety evaluation have also been completed, which provides a timely response to the emerging SARS-CoV-2 variants and vaccine development.
ABSTRACT
Background: The spread of COVID-19 poses a challenge for obstetrics and gynecology (O&G) residents. In order to improve the theoretical knowledge and practical skills of residents in epidemic prevention and control, reduce work pressure and improve professional skills, effective and sound training models are required to improve the protection of O&G residents from COVID-19. Method: A total of 38 standardized training O&G residents working in Shengjing Hospital of China Medical University in March 2020 was selected. They were randomly divided into intervention and control groups. The control group underwent a protection theory exposition according to the traditional training method, while the intervention group adopted a conceive-design-implement-operate (CDIO) mode, arranged training courses in combination with the O&G specialty, and completed four modules of CDIO. After the training, the theoretical knowledge and practical operation were assessed, and the work stress and occupational identity scales were assessed. The assessment results and scores of the two groups of residents were analyzed. Results: Compared with the scores of the residents in the control group, the theoretical and technical scores of the residents in the intervention group significantly improved (P < 0.05). In the evaluation of organizational management, workload, interpersonal relationship, and doctor-patient relationship pressure, the scores of the intervention group were lower than those of the control group, with a statistical difference (P < 0.05). For the intervention group, the job stress and professional identity evaluation scores were significantly higher than those of the control group (P < 0.05). Conclusion: The CDIO model can effectively enhance the theoretical knowledge and practical skills of O&G residents in COVID-19 epidemic prevention protocols to reduce work pressure and improve professional identity. In addition, it provides new ideas, methods, and approaches for future clinical practice training.