Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike's function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants.IMPORTANCENovel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.

Fourth mRNA vaccination increases cross-neutralizing antibody titers against SARS-CoV-2 variants, including BQ.1.1 and XBB, in a very elderly population.

BACKGROUND: Omicron variants with immune evasion have emerged, and they continue to mutate rapidly, raising concerns about the weakening of vaccine efficacy, and the very elderly populations are vulnerable to Coronavirus Disease 2019 (COVID-19). Therefore, to investigate the effect of multiple doses of mRNA vaccine for the newly emerged variants on these populations, cross-neutralizing antibody titers were examined against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, including BQ.1.1 and XBB. METHODS: Blood samples were taken from residents at four long-term care facilities in Hyogo prefecture, Japan (median age, 91 years), after 3rd (n = 67) and 4th (n = 48) mRNA vaccinations, from April to October 2022. A live virus microneutralization assay was performed to determine the neutralizing antibody titers in participants' sera. RESULTS: After 3rd vaccination, cross-neutralizing antibody prevalence against conventional (D614G) virus, Delta, Omicron BA.2, BA.5, BA.2.75, BQ.1.1, and XBB were 100%, 97%, 81%, 51%, 67%, 4%, and 21%, respectively. After 4th vaccination, the antibody positivity rates increased to 100%, 100%, 98%, 79%, 92%, 31%, and 52%, respectively. The 4th vaccination significantly increased cross-neutralizing antibody titers against all tested variants. CONCLUSION: The positivity rates for BQ.1.1 and XBB increased after 4th vaccination, although the titer value was lower than those of BA.5 and BA.2.75. Considering the rapid mutation of viruses and the efficacy of vaccines, it may be necessary to create a system that can develop vaccines suitable for each epidemic in consideration of the epidemic of the virus.

Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants.

We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.

3D Bitemark Analysis in Forensic Odontology Utilizing a Smartphone Camera and Open-Source Monoscopic Photogrammetry Surface Scanning

Abstract Bitemark analysis is a challenging procedure in the field of criminal case investigation. The unique characteristics of dentition are used to find the best match between the existing patterned injury and the suspected perpetrator in bitemark identification. Bitemark analysis accuracy can be influenced by various factors, including biting pressure, tooth morphology, skin elasticity, dental cast duplication, timing, and image quality. This review article discusses the potential of a smartphone camera as an alternative method for 3D bitemark analysis. Bitemark evidence on human skin and food should be immediately recorded or duplicated to retrieve long-lasting proof, allowing for a sufficient examination period. Various studies utilizing two-dimensional (2D) and three-dimensional (3D) technologies have been developed to obtain an adequate bitemark analysis. 3D imaging technology provides accurate and precise analysis. However, the currently available method using an intraoral scanner (IOS) requires high-cost specialized equipment and a well-trained operator. The numerous advantages of monoscopic photogrammetry may lead to a novel method of 3D bitemark analysis in forensic odontology. Smartphone cameras and monoscopic photogrammetry methodology could lead to a novel method of 3D bitemark analysis with an efficient cost and readily available equipment.

Children and Adolescent Dental Age Estimation by the Willems and Al Qahtani Methods in Surabaya, Indonesia.

Objectives: Dental age estimation has been employed in a range of legal operations as well as catastrophe victim identification. Dental age estimation is regarded as an appropriate method for estimating a person's age because there is a high association between age and teeth. This study aims to assess the suitability of the Al Qahtani and Willems dental age estimation approaches for the Indonesian children and adolescent population. Methods: A total of 150 panoramic radiographs of patients (75 boys and 75 girls, 6-17 years old) were obtained from the Department of Radiology, Airlangga University, Indonesia. One researcher analyzed estimated dental age (EDA) twice in a one-week time-lapse using the Willems and Al Qahtani methods. The statistical analysis of the present study was carried out using IBM® SPSS® Statistics version 25.0 (IBM, Armonk, NY, USA). Results: The mean of this study's chronological age (CA) was 11.60 ± 3.41. Using the Willems method, the mean difference between CA and EDA for boys and girls was -0.41 ± 0.90. The mean difference between CA and EDA for boys and girls is 0.33 ± 0.61 using the Al Qahtani method. Conclusions: According to the findings of this investigation, the dental age estimation method proposed by Al Qahtani and Willems can be applied to the population in Surabaya. However, a comprehensive study is required when using this method because the data revealed significant statistical disparities between the two methods.

The Applicable Dental Age Estimation Methods for Children and Adolescents in Indonesia.

Indonesia is an archipelagic country bordered by tectonically active zones with intense seismicity and volcanism. This condition is often associated with a high-risk situation of disasters in Indonesia. Forensic identification is a necessary procedure to reveal an individual's identity. An identity, including sex and age, is needed to build a conclusion of human identification. Dental age estimation is a subfield of forensic odontology which focuses on establishing an individual's age. Tooth development, biochemical, and postformation changes are the parameters for estimating dental age. This review discusses the applicable dental age estimation method for children and adolescents in Indonesia. Several articles that have previously studied dental age estimation in Indonesia were reviewed for this manuscript. On reviewing these articles, it was found that the Demirjian method, the Willems method, and the Al Qahtani method are useful in this population with higher accuracy than other methods.