A bias of Asparagine to Lysine mutations in SARS-CoV-2 outside the receptor binding domain affects protein flexibility.

Introduction: COVID-19 pandemic has been threatening public health and economic development worldwide for over two years. Compared with the original SARS-CoV-2 strain reported in 2019, the Omicron variant (B.1.1.529.1) is more transmissible. This variant has 34 mutations in its Spike protein, 15 of which are present in the Receptor Binding Domain (RBD), facilitating viral internalization via binding to the angiotensin-converting enzyme 2 (ACE2) receptor on endothelial cells as well as promoting increased immune evasion capacity. Methods: Herein we compared SARS-CoV-2 proteins (including ORF3a, ORF7, ORF8, Nucleoprotein (N), membrane protein (M) and Spike (S) proteins) from multiple ancestral strains. We included the currently designated original Variant of Concern (VOC) Omicron, its subsequent emerged variants BA.1, BA2, BA3, BA.4, BA.5, the two currently emerging variants BQ.1 and BBX.1, and compared these with the previously circulating VOCs Alpha, Beta, Gamma, and Delta, to better understand the nature and potential impact of Omicron specific mutations. Results: Only in Omicron and its subvariants, a bias toward an Asparagine to Lysine (N to K) mutation was evident within the Spike protein, including regions outside the RBD domain, while none of the regions outside the Spike protein domain were characterized by this mutational bias. Computational structural analysis revealed that three of these specific mutations located in the central core region, contribute to a preference for the alteration of conformations of the Spike protein. Several mutations in the RBD which have circulated across most Omicron subvariants were also analysed, and these showed more potential for immune escape. Conclusion: This study emphasizes the importance of understanding how specific N to K mutations outside of the RBD region affect SARS-CoV-2 conformational changes and the need for neutralizing antibodies for Omicron to target a subset of conformationally dependent B cell epitopes.

Short-Term Adverse Effects Immediately after the Start of COVID-19 Booster Vaccination in Vietnam.

BACKGROUND: Risk communication is necessary to improve the booster vaccination rate, but Vietnam does not have a system to collect and disclose such information. Therefore, the purpose of this study was to clarify adverse reactions and their frequency in the early period after booster vaccination, and to obtain primary data for improving the booster vaccination rate. METHODS: A cross-sectional survey was conducted among adults aged ≥18 years. Clinical data were collected 14 days after booster vaccination by using a standard questionnaire. RESULTS: A total of 1322 participants were included with median age = 23 and sex ratio (Male/Female) = 0.53. AstraZeneca was the most commonly used vaccine for the first and second doses, while Pfizer was the most commonly used vaccine for booster shots. Injection site pain, fatigue, and myalgia were the most common side effect reported (71.9%, 28.1%, and 21.8%, respectively). Compared to previous COVID-19 vaccine injections, 81.9% of participants reported that their symptoms were similar or milder after receiving the booster dose. They were more likely to present injection site pain (OR = 1.43, p < 0.0001) and lymphadenopathy (OR = 4.76, p < 0.0001) after receiving the booster shot. Fever (OR = 0.33, p < 0.0001) and fatigue (OR = 0.77, p = 0.002) were less often reported after booster shots compared to the first and second injections. The severity of symptoms occurring after booster dose versus first and second doses increased significantly with each additional year of age and among participants receiving the Pfizer and Moderna vaccines. CONCLUSION: Adverse reactions to booster vaccination are minor and their incidence is the same as for the first or the second vaccination. Multicenter studies with larger sample sizes on the side effects and safety of COVID-19 vaccine booster shots need to be conducted to make the population less worried, in order to increase the vaccination rate, to protect individuals' and communities' health.

Seroprevalence of SARS-CoV-2 among high-density communities and hyper-endemicity of COVID-19 in Vietnam.

OBJECTIVE: To assess the magnitude of active and recovering COVID-19 patients among at-risk communities and to identify the factors associated with positive serology. METHODS: Four hundred and eighty-three close contacts of COVID-19 patients residing in Ho Chi Minh City, Vietnam, during the fourth wave of the COVID-19 epidemic (September and October 2021) were included. Five weeks after exposure to a COVID-19 patient, they underwent a serology test using the BIOSYNEX COVID-19 BSS kit. RESULTS: The median age of participants was 37 years. A total of 34.6% individuals presented at least one clinical symptom between the time of contact with the COVID-19 patient and inclusion in study. A total of 1.7% unvaccinated individuals tested positive for SARS-CoV-2 using real-time PCR, and 9.5% had evidence of recent infection (positive PCR and/or IgM). A further 26.7% unvaccinated individuals presented evidence of a past infection (positive IgG only). Socio-demographic characteristics, vaccination status and clinical symptoms were not associated with a positive IgM test. CONCLUSION: This is the first serosurvey conducted during the fourth wave of the epidemic in Vietnam. It revealed a seropositivity rate higher than in previous studies and confirmed the hyperendemicity of SARS-CoV-2. Testing using rapid serological tests proved to be a reliable, easy-to-use method and enabled a rapid estimation of the burden of COVID-19.

Can Glycosylation Mask the Detection of MHC Expressing p53 Peptides by T Cell Receptors?

Proteins of the major histocompatibility complex (MHC) class I, or human leukocyte antigen (HLA) in humans interact with endogenous peptides and present them to T cell receptors (TCR), which in turn tune the immune system to recognize and discriminate between self and foreign (non-self) peptides. Of especial importance are peptides derived from tumor-associated antigens. T cells recognizing these peptides are found in cancer patients, but not in cancer-free individuals. What stimulates this recognition, which is vital for the success of checkpoint based therapy? A peptide derived from the protein p53 (residues 161-169 or p161) was reported to show this behavior. T cells recognizing this unmodified peptide could be further stimulated in vitro to create effective cancer killing CTLs (cytotoxic T lymphocytes). We hypothesize that the underlying difference may arise from post-translational glycosylation of p161 in normal individuals, likely masking it against recognition by TCR. Defects in glycosylation in cancer cells may allow the presentation of the native peptide. We investigate the structural consequences of such peptide glycosylation by investigating the associated structural dynamics.