The respiratory syncytial virus (RSV) fusion (F) glycoprotein prefusion conformation is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies which were substantially more potent than the prophylactic antibody palivizumab. The co-crystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed that D25 locks F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed two other antibodies, AM22 and 5C4, also bind to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and guide new approaches for passive prevention of RSV-induced disease.

The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.

Background: SARS-CoV-2-caused coronavirus disease (COVID-19) is posing a large casualty. The features of COVID-19 patients with and without pneumonia, SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown. Methods: We collected information on clinical characteristics, exposure history, and laboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. Results: We characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42 (95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to conversion was 9.71 (95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared to patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/µL) of CD8 + T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 and lactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course, T lymphocytes were .CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not peer-reviewed) The copyright holder for this preprint .

Background: The E2s domain of hepatitis E virus (HEV) capsid protein is the major target for antibody response. Results: Six antigenic sites of the E2s domain were identified by constructing, clustering, and characterizing a tool box containing representative anti-HEV monoclonal antibodies. Conclusion:The comprehensive functional epitopes of E2s domain were identified. Significance: This study provided a novel method for the comprehensive characterization of conformational antigenic domains.

p239 is a virus-like particle constituted from hepatitis E virus (HEV) recombinant proteins. It can be used as a surrogate for HEV and as an investigative tool to study cellular interactions because of its ability to adsorb to and penetrate HepG2 cellular membranes. Our objective was to use p239 to define the role of HEV capsid proteins during the early stages of infection. Pull-down and MALDI-TOF MS experiments identified three host-cell proteins, Grp 78/Bip, a-tubulin and heatshock protein 90 (HSP90), and the latter was investigated further. Antibodies to p239 alone or HSP90 alone could detect p239 or HSP90, suggesting the formation of a complex between p239 and HSP90. In the HepG2 cell, geldanamycin (GA), an HSP90-specific inhibitor, blocked intracellular transportation of p239, but had no effect on the binding and cellular entry of p239, suggesting that HSP90 was important for HEV capsid intracellular transportation. RT-PCR results showed that the efficiency of wild-type HEV infection was inhibited significantly by GA treatment, suggesting the importance of HSP90 in virus infectivity. It was concluded that HSP90 plays a crucial role in the intracellular transportation of viral capsids in the early stage of HEV infection.

A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines.

Background Cardiovascular disease (CVD) was in common in Coronavirus Disease 2019 (COVID-19) patients and associated with unfavorable outcomes. We aimed to compare the clinical observations and outcomes of SARS-CoV-2-infected patients with or without CVD. Methods Patients with laboratory-confirmed SARS-CoV-2 infection were clinically evaluated at Wuhan Seventh People’s Hospital, Wuhan, China, from January 23 to March 14, 2020. Demographic data, laboratory findings, comorbidities, treatments and outcomes were collected and analyzed in COVID-19 patients with and without CVD. Results Among 596 patients with COVID-19, 215 (36.1%) of them with CVD. Compared with patients without CVD, these patients were significantly older (66 years vs 52 years) and had higher proportion of men (52.5% vs 43.8%). Complications in the course of disease were more common in patients with CVD, included acute respiratory distress syndrome (22.8% vs 8.1%), malignant arrhythmias (3.7% vs 1.0%) including ventricular tachycardia/ventricular fibrillation, acute coagulopathy(7.9% vs 1.8%), and acute kidney injury(11.6% vs 3.4%). The rate of glucocorticoid therapy (36.7% vs 25.5%), Vitamin C (23.3% vs 11.8%), mechanical ventilation (21.9% vs 7.6%), intensive care unit admission (12.6% vs 3.7%) and mortality (16.7% vs 4.7%) were higher in patients with CVD (both p &lt; 0.05). The multivariable Cox regression models showed that older age (≥65 years old) (HR 3.165, 95%CI 1.722-5.817) and patients with CVD (HR 2.166, 95%CI 1.189-3.948) were independent risk factors for death. Conclusions CVD are independent risk factors for COVID-19 patients. COVID-19 patients with CVD were more severe and had higher mortality rate, early intervention and vigilance should be taken.

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