The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-speci c antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV. Background The outbreaks of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) in 2002/2003 and those of middle east respiratory syndrome (MERS) caused by MERS coronavirus (MERS-CoV) in 2012 have highlighted the high zoonotic potential of emerging coronaviruses 1, 2. The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus 2019 (2019-nCoV) 3 , which was also denoted as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 4 , or human coronavirus 2019 (HCoV-19) 5 , has resulted in more than 17 million con rmed cases and 0.66 million deaths in 216 countries, areas or territories (https://www.who.int/), endangering the global public health and economy and thus calling for the development of effective vaccines to protect at-risk populations. Currently, more than 150 COVID-19 vaccines are under development at different stages 6-9. Especially, a number of COVID-19 vaccines' phase 1/2 clinical trials have been completed, including the adenovirusvectored vaccines (Ad5-nCoV and ChAdOx1 nCoV-19) from CanSino 10 and Oxford University/AstraZeneca 11 , respectively; the mRNA vaccines (mRNA-1273 and BNT162b1) from Moderna 12 and P zer/BioNTech 13 , respectively; and the inactivated vaccines (PiCoVacc and BBIBP-CorV) from Sinovac 14 and Beijing Institute of Biological Products 15 , respectively (https://biorender.com/covid-vaccine-tracker/). Generally speaking, all these vaccines could induce antibodies speci c for spike (S) protein and receptor-binding domain (RBD), which neutralized pseudotyped and live SARS-CoV-2 infection. Some reports have shown that the neutralizing antibody titers are strongly correlated with RBD-binding IgG ...
We predict a new class of monolayer phosphorus allotropes, namely, ε-P, ζ-P, η-P, and θ-P. Distinctly different from the monolayer α-P (black) and previously predicted β-P (Phys. Rev. Lett. 2014, 112, 176802), γ-P, and δ-P (Phys. Rev. Lett. 2014, 113, 046804) with buckled honeycomb lattice, the new allotropes are composed of P4 square or P5 pentagon units that favor tricoordination for P atoms. The new four polymorphs, together with five additional hybrid polymorphs, greatly enrich the phosphorene structures, and their stabilities are confirmed by first-principles calculations. In particular, the θ-P is shown to be equally stable as the α-P (black) and more stable than all previously reported phosphorene polymorphs. Prediction of nonvolatile ferroelastic switching and structural transformation among different polymorphs under strains points out their potential applications via strain engineering.
Background Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3–17 years. Methods A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3–5 years, 6–12 years, or 13–17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn , ChiCTR2000032459, and is ongoing. Findings Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 μg] in each of three age cohorts [3–5, 6–12, and 13–17 years]) or control (n=72, 24 for each age cohort [3–5, 6–12, and 13–17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 μg] in each of three age cohorts [3–5, 6–12, and 13–17 years]) or control (n=180, 60 for each age cohort [3–5, 6–12, and 13–17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3–5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6–12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13–17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3–5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6–12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13–17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT agains...
3This article deals with averaging principle for stochastic hyperbolic-parabolic equations with slow and 4 fast time-scales. Under suitable conditions, the existence of an averaging equation eliminating the fast 5 variable for this coupled system is proved. As a consequence, an effective dynamics for slow variable 6 which takes the form of stochastic wave equation is derived. Also, the rate of strong convergence for the 7 slow component towards the solution of the averaging equation is obtained as a byproduct. 8 c ⃝ 2015 Published by Elsevier B.V. 9 MSC: primary 60H15; secondary 70K70 10
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