Fortuitous Somatic Mutations during Antibody Evolution Endow Broad Neutralization against SARS-CoV-2 Omicron Variants

Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

A potent SARS-CoV-2 antibody neutralizes Omicron variant by disassembling the spike trimer

The continuous emergence of novel SARS-CoV-2 variants poses new challenges to the fight against the COVID-19 pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of antibody targeting conserved and universal epitope is urgently needed. A subset neutralizing antibody(nAbs) against COVID-19 from convalescent patients were isolated in our previous study. Here in this study, we investigated the accommodation of these nAbs to SARS-CoV-2 variants of concerns (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of SARS-CoV-2 Omicron variant. In addition, we determined the cryo-EM structure of SARS-CoV-2 spike complexed with three antibodies targeting different epitopes, including 553-49, 553-15 and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes virus by disassembling spike trimers. 553-15, an antibody that neutralizes all the other VOCs except omicron, cross-links two spike trimers to form trimer dimer, demonstrating that 553-15 neutralizes virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 49 and other antibody targeting this highly conserved epitope as promising cocktail therapeutics reagent for COVID-19. ImportanceThe newly emergence of Omicron strain caused higher immune escape, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. In this study, we identified a SARS-CoV-2 Omicron neutralizing antibody 553-49, which neutralizes Omicron variant by targeting a completely conserved novel epitope. Besides, we revealed that IgG 553-15 neutralizes SARS-CoV-2 by crosslinking virions and 553-60 functions by blocking receptor binding. Comparison of different RBD epitopes revealed that the epitope of 553-49 is hidden in the S trimer and keeps high conservation during SARS-CoV-2 evolution, making 553-49 a promising therapeutics reagent to fight against the emerging Omicron and future variant of SARS-CoV-2.

Effect and mechanism of Guanxin-Shutongcapsule in the treatment of arterial elasticity on the patients with hypertension / 国际中医中药杂志

Objective To observe the effect ofGuanxin-Shutongcapsule in the treatment of arterial elasticity on patients with hypertension.Methods The hypertension patients who met the inclusion criteria were divided into treatment group (50 cases) and control group (52 cases). The control group was treated with antihypertensive drugs to control blood pressure within the normal range. The treatment group was treated withGuanxin-Shutongcapsule on the basis of the control group. All were given 8 weeks treatment. The main artery elastic parameters were meansured by the carotid-femoral pulse wave velocity (C-FPWV) and cervical-dorsal arterial pulse wave velocity (C-DPWV). The immune turbidimetric method was employed to enhance for the determination of high sensitive C reactive protein (hs-CRP); and radioimmunoassay was used to assess the serum IL-6, TNF-a, triglyceride (TG) and total cholesterol (TC). The blood pressure was monitored during the treatment.Results After the treatment, the level of hs-CRP (2.83 ± 1.35 mg/Lvs. 3.65 ± 1.38 mg/L,t=6.357), TNF-α (0.16 ± 0.08 mg/Lvs. 0.28 ± 0.07 mg/L,t=18.213), C-FPWV (13.85 ± 1.86 m/svs. 15.34 ± 1.78 m/s,t=6.524), C-DPWV (11.98 ± 1.45 m/svs. 12.87 ± 1.48 m/s,t=7.152) in treatment group was significantly lower than those in the control group (P<0.01).ConclusionGuanxin-Shutong capsule by inhibiting systemic inflammation, reducing and reversing atherosclerosis, and improving the arterial elasticity and blood pressure.

Relationship between current smoking behaviors and household characteristics in Guangdong / 中华流行病学杂志

Objective To disclose the relationship between current smoking behaviors and household characteristics among adults in Guangdong,in order to provide scientific evidence for household tobacco control strategy. Methods A questionnaire survey was conducted among the adults sampled by four-stage randomized cluster sampling in ten districts of five cities in Guangdong from September to November,2010. The questionnaire included demographic characteristics,smoking behaviors and smoking-related household characteristics. Chi-square test and unconditional logistic regression analysis were employed to explore the relationship between current smoking behaviors and household characteristics. Results This study included 2 150 respondents,with data from 2 121 eligible questionnaires used for analysis. The current smoking rates for respondents with household characteristics including per capita household income below 1 000 Yuan,three or more smokers in the family,no ban of smoking at home and treating visitors with cigarettes were 28.7%,56.5%,34.2%and 43.5%,respectively,and were significantly higher than those for respondents with household characteristics at other levels(P<0.01 for all). After controlling for factors such as gender,age, personal income,education,employment status and residential location,we found that the number of family smokers,smoking restrictions at home and treating visitors with cigarettes had significant association with current smoking behaviors(P<0.01 for all),except for per capita household income (P=0.567). Conclusion Household is one of the effective places in carrying out health education and tobacco control intervention. In order to reduce tobacco use,much effort should be made to create smoke-free homes,encourage smoking cessation and treat visitors with no cigarettes.

Relationship between current smoking behaviors and household characteristics in Guangdong / 中华流行病学杂志

Objective To disclose the relationship between current smoking behaviors and household characteristics among adults in Guangdong,in order to provide scientific evidence for household tobacco control strategy. Methods A questionnaire survey was conducted among the adults sampled by four-stage randomized cluster sampling in ten districts of five cities in Guangdong from September to November,2010. The questionnaire included demographic characteristics,smoking behaviors and smoking-related household characteristics. Chi-square test and unconditional logistic regression analysis were employed to explore the relationship between current smoking behaviors and household characteristics. Results This study included 2 150 respondents,with data from 2 121 eligible questionnaires used for analysis. The current smoking rates for respondents with household characteristics including per capita household income below 1 000 Yuan,three or more smokers in the family,no ban of smoking at home and treating visitors with cigarettes were 28.7%,56.5%,34.2%and 43.5%,respectively,and were significantly higher than those for respondents with household characteristics at other levels(P<0.01 for all). After controlling for factors such as gender,age, personal income,education,employment status and residential location,we found that the number of family smokers,smoking restrictions at home and treating visitors with cigarettes had significant association with current smoking behaviors(P<0.01 for all),except for per capita household income (P=0.567). Conclusion Household is one of the effective places in carrying out health education and tobacco control intervention. In order to reduce tobacco use,much effort should be made to create smoke-free homes,encourage smoking cessation and treat visitors with no cigarettes.

Relationship between current smoking behaviors and household characteristics in Guangdong / 中华流行病学杂志

<p><b>OBJECTIVE</b>To disclose the relationship between current smoking behaviors and household characteristics among adults in Guangdong, in order to provide scientific evidence for household tobacco control strategy.</p><p><b>METHODS</b>A questionnaire survey was conducted among the adults sampled by four-stage randomized cluster sampling in ten districts of five cities in Guangdong from September to November, 2010. The questionnaire included demographic characteristics, smoking behaviors and smoking-related household characteristics. Chi-square test and unconditional logistic regression analysis were employed to explore the relationship between current smoking behaviors and household characteristics.</p><p><b>RESULTS</b>This study included 2 150 respondents, with data from 2 121 eligible questionnaires used for analysis. The current smoking rates for respondents with household characteristics including per capita household income below 1 000 Yuan, three or more smokers in the family, no ban of smoking at home and treating visitors with cigarettes were 28.7%, 56.5%, 34.2% and 43.5% , respectively, and were significantly higher than those for respondents with household characteristics at other levels (P < 0.01 for all). After controlling for factors such as gender, age, personal income, education, employment status and residential location, we found that the number of family smokers, smoking restrictions at home and treating visitors with cigarettes had significant association with current smoking behaviors (P < 0.01 for all), except for per capita household income (P = 0.567).</p><p><b>CONCLUSION</b>Household is one of the effective places in carrying out health education and tobacco control intervention. In order to reduce tobacco use, much effort should be made to create smoke-free homes, encourage smoking cessation and treat visitors with no cigarettes.</p>