ABSTRACT
The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A, oral polio vaccine, and smallpox proved to be reliable approaches for immunization for prolonged periods. During the pandemic, we produced an inactivated SARS-CoV-2 vaccine candidate, having the advantages of being manufactured rapidly and tested easily in comparison with recombinant vaccines. In this study, an inactivated virus vaccine that includes a gamma irradiation process for the inactivation as an alternative to classical chemical inactivation methods so that there is no extra purification required has been optimized. The vaccine candidate (OZG-38.61.3) was then applied in mice by employing the intradermal route, which decreased the requirement of a higher concentration of inactivated virus for proper immunization, unlike most of the classical inactivated vaccine treatments. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 1013 or 1014 viral copy per dose) of OZG-38.61.3 was initially determined in Balb/c mice. This was followed by testing the immunogenicity and protective efficacy of OZG-38.61.3. Human ACE2-encoding transgenic mice were immunized and then infected with a dose of infective SARS-CoV-2 virus for the challenge test. Findings of this study show that vaccinated mice have lower SARS-CoV-2 viral copy number in oropharyngeal specimens along with humoral and cellular immune responses against the SARS-CoV-2, including the neutralizing antibodies similar to those shown in Balb/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.
ABSTRACT
BACKGROUND: This study evaluated the effectiveness of the ThinPrep(®) Imaging System (TIS) and ThinPrep(®) Pap Stain (TPPS). A comparative analysis was conducted to determine the detection rates of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), the ASC:squamous intraepithelial lesion (SIL) ratio, biopsy follow-up for ASC-H in terms of the screening method used (manual screening [MS] vs. TIS screening [TISS]) and the staining protocol (regular Pap stain [RPS] vs. TPPS). METHODS: This study was performed over two periods. The RPS period included manually screened slides, whereas the TPPS period included TIS + manually screened slides. All data from the study periods were compared using statistical analysis. RESULTS: The detection rate of ASC-H was significantly higher during the TPPS period than during the RPS period (0.49% vs. 0.23%); this finding is in contrast to the insignificant difference between the screening method periods. The positive predictive value (PPV) of ASC-H cytodiagnosis for cervical intraepithelial neoplasia of grade 2 or more severe histologies was significantly different between manually screened and TIS slides (22.10% vs. 38.55%), in contrast to an insignificant difference between RPS and TPPS periods (37.14% vs. 29.77%). CONCLUSION: Implementation of the TIS did not change the ASC-H detection rates appreciably. However, the new technology improved PPV for ASC-H cytodiagnosis and enabled the detection of true disease. Our laboratory statistics indicate that the TPPS is not a superior staining protocol and did not increase our diagnostic accuracy for ASC-H compared with RPS.
