• IEEE Access Special Section Editorial: Security and Privacy in Emerging Decentralized Communication Environments

      Cheng, Xiaochun; Liu, Zheli; DU, XIAOJIANG; Yu, Shui; Mostarda, Leonardo; Du|0000-0003-4235-9671 (2021-05-13)
      Due to the COVID-19 epidemic, face-to-face team working has changed into distanced work from home. Modern, decentralized digital communication environments are changing with the availability of new technologies and the development of new real-world applications, which lead to novel challenges in security and privacy protection. 5G/6G mobile applications, the smart Internet of Things (IoT) devices, big data applications, and cloud systems are developing to better meet new requirements. Mobile–cloud architecture is emerging as 5G /6G mobile IoT devices are generating large volumes of data which need cloud infrastructure to process. Many IoT systems and cloud systems are decentralized, and new security and privacy protection solutions are emerging in decentralized networks. The increasing interdependence of IT solutions accepted by society has led to a sharp increase in data. As a result, the chances of data leakage or privacy infringement also increase, along with the need for new solutions for digital security and privacy protection.
    • Impact of Tobacco Smoking Status on Morbidity and Mortality in Patients Hospitalized with COVID-19 Pneumonia: Observational study

      Fernandez Romero, Gustavo; Dominguez-Castillo, Eduardo; Zheng, Matthew; Yousef, Ibraheem; Darnell, Melinda; Ganghemi, Andrew; Dorey-Stein, Zack; Zantah, Massa; Townsend, Ryan; Myers, Catherine; Ku, Tse-Shuen; Patel, Maulin; Patlakh, Nicole; Jacobs, Michael; Zhao, Huaqing; Gupta, Rohit; Rali, Parth; Criner, Gerard J. (2020-11-14)
      Background: Determine the impact of tobacco smoking status on patients hospitalized with COVID-19 pneumonia in the need for ICU care, mechanical ventilation and mortality. Methods: We performed a retrospective cohort study, that involved chart review. All adults 18 years or older with a diagnosis of COVID-19 pneumonia hospitalized from March 15th, 2020 to May 06th, 2020 with a positive reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab for COVID-19. We used chi-squared test for categorical variables and student t-tests or Wilcoxon rank sum tests for continuous variables. We further used adjusted and unadjusted logistic regression to assess risk factors for mortality and intubation. Results: Among 577 patients hospitalized with COVID-19 pneumonia, 268 (46.4%) had a history of smoking including 187 former and 81 active smokers. The former smokers when compared with non-smokers were predominantly older with more comorbidities. Also, when compared with never smokers D Dimer levels were elevated in active (p=0.05) and former smokers (p<0.01). The former smokers versus non-smokers required increased need for advanced non-invasive respiratory support on admission (p<0.05), ICU care (p<0.05) and had higher mortality [1.99 (CI 95% 1.03-3.85, p<0.05)]. Active smokers versus non-smokers received more mechanical ventilation [OR 2.11 (CI 95% 1.06-4.19, p<0.05)]. Conclusions: In our cohort of hospitalized patients with COVID-19 pneumonia, former smokers had higher need for non-invasive respiratory support on admission, ICU care, and mortality compared to non-smokers. Also, active smokers versus non-smokers needed more mechanical ventilation.
    • Implications of COVID-19−associated Coagulopathy on Reconstructive Surgery: A Case of Ongoing Tissue Necrosis

      Dugue, David; Hsu, Kun-Tai; Wagner, I. Janelle; Jones, Christine M. (2020-12-16)
    • Incorporating Geographic Information Science and Technology in Response to the COVID-19 Pandemic

      Smith, Charlotte D.; Mennis, Jeremy; 0000-0001-6319-8622 (2020-07-09)
      Incorporating geographic information science and technology (GIS&T) into COVID-19 pandemic surveillance, modeling, and response enhances understanding and control of the disease. Applications of GIS&T include 1) developing spatial data infrastructures for surveillance and data sharing, 2) incorporating mobility data in infectious disease forecasting, 3) using geospatial technologies for digital contact tracing, 4) integrating geographic data in COVID-19 modeling, 5) investigating geographic social vulnerabilities and health disparities, and 6) communicating the status of the disease or status of facilities for return-to-normal operations. Locations and availability of personal protective equipment, ventilators, hospital beds, and other items can be optimized with the use of GIS&T. Challenges include protection of individual privacy and civil liberties and closer collaboration among the fields of geography, medicine, public health, and public policy.
    • Individual Hurricane Preparedness During the COVID-19 Pandemic: Insights for Risk Communication and Emergency Management Policies

      Botzen, W.J.W.; Mol, Jantsje M.; Robinson, Peter John; Zhang, Juan; Czajkowski, Jeffrey (2020-01-01)
      Climate change adaptation strategies should anticipate that the 2020 situation which resembles an above average hurricane season coinciding with a pandemic may occur more frequently in the future. This study draws lessons on how individual hurricane preparedness is influenced by a pandemic, which turns out to be a combination of perceptions of flood and pandemic risks that have opposite effects on preparedness behavior. We conducted three waves of surveys during 2019-2020 to monitor hurricane preparedness activities in flood-prone coastal areas in Florida, including a survey of 600 respondents in early June 2020 to obtain insights into households’ risk perceptions and preparedness for this hurricane season under COVID-19. The results show that this hurricane season is dominated by concerns over COVID-19 which influences people’s evacuation intentions. Whereas hotel costs were the main obstacle to evacuating during Hurricane Dorian in 2019, the main evacuation obstacle identified in the 2020 hurricane season is COVID-19. Our statistical analyses that investigates the factors influencing evacuation intentions consistently show that older individuals are less likely to evacuate voluntarily, because they are concerned about becoming infected by COVID-19. We discuss the implications of our findings for adaptation policies that aim to improve hurricane preparedness in situations of a pandemic, such as risk communication and emergency management policies.
    • Inside the Clockwork of the ECHO Factorial Trial: A Conceptual Model With Proposed Mediators for Prevention of Emotional Problems in Children

      Ingul, Jo Magne; Martinsen, Kristin; Adolfsen, Frode; Sund, Anne Mari; Ytreland, Kristin; Valmyr Bania, Elisabeth; Lisøy, Carina; Potulski Rasmussen, Lene-Mari; Haug, Ida Mari; Patras, Joshua; Collins, Linda M.; Kendall, Philip C.; Neumer, Simon Peter; Kendall|0000-0001-7034-6961 (2021-06-21)
      Having interventions that are not only evidence-based and effective but also cost-effective and efficient is important for the prevention and treatment of child and adolescent emotional problems. A randomized clinical trial (RCT) tests the total interventions effect but does not address specific components of the intervention. In this article the hypothesis and a conceptual model of the ECHO study are presented and discussed. The ECHO intervention consists of three different components each containing two levels of intervention. By using a cluster randomized factorial design, children aged 8–12 at 40 schools across Norway will be randomized to eight different experimental conditions investigating the optimal balance between effect, cost-effectiveness, and efficiency. The article presents the design and the different components being tested and discusses how optimalization can be reached through this innovative design. The article also discusses how interventions can be improved by investigating and understanding the mechanisms of change within psychological interventions. For each of the three components in the study we consider the mediators that could be active within the intervention and how the study investigates such mediation. The results will contribute to a better understanding of how psychological interventions work and how we intend to optimize the EMOTION intervention.
    • International Law as Hedging: Perspectives from Secondary Authoritarian States

      Nguyen, Trang (Mae) (2020-08-17)
      Tom Ginsburg's important article comes at a critical time. The COVID-19 crisis has spurred heated debates about political regimes vis-à-vis countries’ bureaucratic capacity. Political regime type is the core independent variable in Ginsburg's conceptualization of authoritarian international law—a global projection of authoritarian states’ domestic politics. This essay echoes Ginsburg's insightful observation but complicates it by shifting the focus to the less-known perspectives of secondary authoritarian countries. I use a matrix case study of two smaller states, Vietnam and Cambodia, on two prominent issues, the South China Sea (SCS) and the Belt and Road Initiative (BRI), to demonstrate small states’ effort to use international law to “hedge” big powers. As the case studies show, small authoritarian states, not unlike other small states, prefer a pluralist vision of international law, even if they may at times embrace the alternative model offered by big authoritarian powers. These states thus have an important, perhaps unexpected, role to play in preserving the pluralist international legal order and mitigating the hegemonic tendencies of authoritarian international law.
    • Internet Access and Usage Among Stroke Survivors and Their Informal Caregivers: Cross-sectional Study

      Ali Naqvi, Imama; Montiel, Tahani Casameni; Bittar, Yazan; Hunter, Norma; Okpala, Munachi; Johnson, Constance; Weiner, Mark G.; Savitz, Sean; Sharrief, Anjail; Sanner Beauchamp, Jennifer Elizabeth; Bittar|0000-0001-6788-7310 (2021-08-03)
      Background: Web-based interventions have shown promise for chronic disease management but have not been widely applied to populations with stroke. Existing barriers may inhibit the adoption of web-based interventions among stroke survivors and necessitate the involvement of informal caregivers. However, limited information is available on internet accessibility and usability among stroke survivors and their caregivers. Objective: This study aims to investigate internet access and usage in a cohort of stroke survivors and their caregivers. Methods:A cross-sectional survey was conducted with 375 participants (248 stroke survivors and 127 caregivers). Descriptive statistics were generated using cross-tabulation. Comparisons with categorical data were conducted using the chi-square test, whereas the Mann-Whitney U test was used for comparisons involving ordinal variables. Results: Overall, 86.1% (323/375) of the participants reported having internet access. Caregivers were more likely than stroke survivors to access the internet (N=375, χ21=18.5, P<.001) and used text messaging (n=321, χ21=14.7, P<.001). Stroke survivors and caregivers with internet access were younger than stroke survivors and caregivers without internet access. The highest number of participants who reported internet access were non-Hispanic White. Smartphones were the most common devices used to access the internet. Email was the most common type of internet usage reported. Patients who survived for >12 months after a stroke reported higher internet access than those who survived <3 months (P<.001). The number of hours per week spent using the internet was higher for caregivers than for stroke survivors (P<.001). Conclusions: Future feasibility and acceptability studies should consider the role of the informal caregiver, participant age, race and ethnicity, the use of smartphone apps, email and text correspondence, and the amount of time elapsed since the stroke event in the design and implementation of web-based interventions for populations with stroke.
    • Intersection of the Web-Based Vaping Narrative With COVID-19: Topic Modeling Study

      Janmohamed, Kamila; Soale, Abdul-Nasah; Forastiere, Laura; Tang, Weiming; Sha, Yongjie; Demant, Jakob; Airoldi, Edoardo; Kumar, Navin; Soale|0000-0003-2093-7645; Airoldi|0000-0002-3512-0542 (2020-10-30)
      Background: The COVID-19 outbreak was designated a global pandemic on March 11, 2020. The relationship between vaping and contracting COVID-19 is unclear, and information on the internet is conflicting. There is some scientific evidence that vaping cannabidiol (CBD), an active ingredient in cannabis that is obtained from the hemp plant, or other substances is associated with more severe manifestations of COVID-19. However, there is also inaccurate information that vaping can aid COVID-19 treatment, as well as expert opinion that CBD, possibly administered through vaping, can mitigate COVID-19 symptoms. Thus, it is necessary to study the spread of inaccurate information to better understand how to promote scientific knowledge and curb inaccurate information, which is critical to the health of vapers. Inaccurate information about vaping and COVID-19 may affect COVID-19 treatment outcomes. Objective: Using structural topic modeling, we aimed to map temporal trends in the web-based vaping narrative (a large data set comprising web-based vaping chatter from several sources) to indicate how the narrative changed from before to during the COVID-19 pandemic. Methods: We obtained data using a textual query that scanned a data pool of approximately 200,000 different domains (4,027,172 documents and 361,100,284 words) such as public internet forums, blogs, and social media, from August 1, 2019, to April 21, 2020. We then used structural topic modeling to understand changes in word prevalence and semantic structures within topics around vaping before and after December 31, 2019, when COVID-19 was reported to the World Health Organization. Results: Broadly, the web-based vaping narrative can be organized into the following groups or archetypes: harms from vaping; Vaping Regulation; Vaping as Harm Reduction or Treatment; and Vaping Lifestyle. Three archetypes were observed prior to the emergence of COVID-19; however, four archetypes were identified post–COVID-19 (Vaping as Harm Reduction or Treatment was the additional archetype). A topic related to CBD product preference emerged after COVID-19 was first reported, which may be related to the use of CBD by vapers as a COVID-19 treatment. Conclusions: Our main finding is the emergence of a vape-administered CBD treatment narrative around COVID-19 when comparing the web-based vaping narratives before and during the COVID-19 pandemic. These results are key to understanding how vapers respond to inaccurate information about COVID-19, optimizing treatment of vapers who contract COVID-19, and possibly minimizing instances of inaccurate information. The findings have implications for the management of COVID-19 among vapers and the monitoring of web-based content pertinent to tobacco to develop targeted interventions to manage COVID-19 among vapers.
    • Investigating the Relationships Between Public Health Literacy and Public Trust in Physicians in China's Control of COVID-19: A Cross-Sectional Study

      Chen, Dongjin; Zhou, Qian; Pratt, Cornelius B.; Su, Zhenhua; Gu, Zheng (2021-10-28)
      Objective: Public trust in physicians and public health literacy (HL) are important factors that ensure the effectiveness of health-care delivery, particularly that provided during the SARS-CoV-2 pandemic. This study investigates HL as a predictor of public trust in physicians in China's ongoing efforts to control COVID-19. Methods: Data were gathered in February 2020 during the peak of the disease in China. Based on Nutbeam's conceptualization of HL, we measure HL vis-à-vis COVID-19 by using a six-item scale that includes two items each for functional, interactive, and critical HL. Trust in physicians was measured by assessing physicians' capability to diagnose COVID-19. A rank-sum test and ordinal logit regression modeling were used to analyze the data. Results: Two key findings: (a) trust in physician handling of treatment for COVID-19 is reported by about 74% of respondents; and (b) five of the six HL measures are positive predictors of public trust in physician treatment of the disease, with functional HL1 having the highest level of such association (coefficient 0.285, odds ratio 1.33%, p < 0.01). Conclusions: Improving public HL is important for better public-physician relationships, as well as for nations' efforts to contain the pandemic, serving as a possible behavioral, non-clinical antidote to COVID-19. Being confronted with the unprecedented virus, humans need trust. Health education and risk communication can improve public compliance with physicians' requirements and build a solid foundation for collective responses.
    • let-7 microRNAs: Their Role in Cerebral and Cardiovascular Diseases, Inflammation, Cancer, and Their Regulation

      Center for Substance Abuse Research (Temple University) (2021-05-26)
      The let-7 family is among the first microRNAs found. Recent investigations have indicated that it is highly expressed in many systems, including cerebral and cardiovascular systems. Numerous studies have implicated the aberrant expression of let-7 members in cardiovascular diseases, such as stroke, myocardial infarction (MI), cardiac fibrosis, and atherosclerosis as well as in the inflammation related to these diseases. Furthermore, the let-7 microRNAs are involved in development and differentiation of embryonic stem cells in the cardiovascular system. Numerous genes have been identified as target genes of let-7, as well as a number of the let-7’ regulators. Further studies are necessary to identify the gene targets and signaling pathways of let-7 in cardiovascular diseases and inflammatory processes. The bulk of the let-7’ regulatory proteins are well studied in development, proliferation, differentiation, and cancer, but their roles in inflammation, cardiovascular diseases, and/or stroke are not well understood. Further knowledge on the regulation of let-7 is crucial for therapeutic advances. This review focuses on research progress regarding the roles of let-7 and their regulation in cerebral and cardiovascular diseases and associated inflammation.
    • Lung transplantation and coronavirus disease 2019 (COVID-19): a roadmap for the enduring pandemic

      Shigemura, Norhisa; Cordova, Francis; Hayanga, Awori J.; Criner, Gerard; Toyoda, Yoshiya (2021-11-05)
      Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic, organ transplant specialists remain uncertain of directions and goals before and after organ replacement therapy (1). Reports of COVID-19 outcomes in lung transplant recipients have been limited, comprising a small number of case series without a consistent approach between those infected post-transplant and those who became candidates for a transplant post-infection (2-5). Nonetheless, the pandemic has inspired new roles for lung failure specialists who must care for patients who develop acute respiratory distress syndrome (ARDS) and progressive pulmonary fibrosis due to COVID-19 (6). Specialists who can handle organ replacement therapy including extracorporeal membrane oxygenation (ECMO) and lung transplantation are an integral part of the multidisciplinary care team (2,7). In the midst of the first phase of the pandemic, we offered our insights regarding the direction of lung transplantation during the pandemic as specialists at a high-volume center in a geographical area with high COVID-19 infection rates (8). Herein, we expand our review of outcomes in lung transplant recipients with COVID-19 infections and offer our phased approach as well as insights for lung transplantation for post covid lung failure as the sequelae of COVID-19 infection in light of our large outcomes data for the recipients with positive covid after lung transplantation.
    • Males Receive Low-Tidal Volume Component of Lung Protective Ventilation More Frequently than Females in the Emergency Department

      Isenberg, Derek L.; Bloom, Benjamin; Gentile, Nina; Reimer, Hannah; Glaze, Owen D.; Palumbo, Paige; Fenstermacher, Rachel (2020)
      Introduction: Mechanical ventilation is a commonly performed procedure in the emergency department (ED). Approximately 240,000 patients per year receive mechanical ventilation in the ED representing 0.23% of ED visits. An ED-based trial published in 2017 showed that a bundle of interventions in mechanically ventilated patients, including low tidal volume ventilation, reduced the development of acute respiratory distress syndrome by nearly 50%. Prior literature has shown that as many as 40% of ED patients do not receive lung protective ventilation. Our goal was to determine whether differences exist between the percent of males vs females who are ventilated at ≥ 8 milliliters per kilogram (mL/kg) of predicted body weight. Methods: We conducted this study at Temple University Hospital, a tertiary care center located in Philadelphia, Pennsylvania. This was a planned subgroup analysis of study looking at interventions to improve adherence to recommended tidal volume settings. We used a convenience sample of mechanically ventilated patients in our ED between September 1, 2017, and September 30, 2018. All adult patient > 18 years old were eligible for inclusion in the study. Our primary outcome measure was the number of patients who had initial tidal volumes set at > 8 mL/kg of predicted body weight. Our secondary outcome was the number of patients who had tidal volumes set at ≥ 8 mL/kg at 60 minutes after initiation of mechanical ventilation. Results: A total of 130 patients were included in the final analysis. We found that significantly more females were initially ventilated with tidal volumes ≥ 8 mL/kg compared to men: 56% of females vs 9% of males (p=<0.001). Data was available for 107 patients (82%) who were in the ED at 60 minutes after initiation of mechanical ventilation. Again, a significantly larger percentage of females were ventilated with tidal volumes ≥ 8 mL/kg at 60 minutes: 56% of females vs 10% of males (p<0.001). Conclusion: The vast majority of tidal volumes ≥ 8 mL/kg during mechanical ventilation occurs in females. We suggest that objective measurements, such as a tape measure and tidal volume card, be used when setting tidal volumes for all patients, especially females.
    • Managing through a crisis: Managerial implications for business-to-business firms

      Pedersen, Carsten Lund; Ritter, Thomas; Di Benedetto, C. Anthony (2020-06-05)
    • Material Hardship Among Custodial Grandparents and Grandchildren's Physical and Mental Health in COVID-19

      Xu, Yanfeng; Zhao, Qianwei; Schuler, Brittany; Levkoff, Sue; Schuler|0000-0002-2869-6260 (2021-12-17)
      COVID-19 has increased economic hardship for many families, including custodial grandparent-headed families. We aim to examine latent classes of material hardship among custodial grandparent-headed families, to assess predictors associated with identified classes, and to investigate associations with grandchildren’s physical and mental health outcomes during COVID-19. Data was collected from a cross-sectional survey in June 2020. The sample comprised of 362 grandparents. Latent class analysis and logistic regression were conducted. Three latent classes of material hardship were identified: Class 1 (n = 232; 64.1%) low overall hardship with high medical hardship, class 2 (n = 52; 14.4%) moderate overall hardship with high utility hardship, and class 3 (n = 78; 21.5%) severe overall hardship. Factors, such as race, household income, labor force status, financial assistance status, and trigger events to raise grandchildren, were associated with class membership. Class 2 (OR = 0.19, p < 0.05) compared to Class 1 was significantly associated with grandchildren’s physical health. Our findings suggest that material hardship is heterogeneous among custodial grandparents during COVID-19, and children in households experiencing utility hardship have a higher risk for poorer physical health outcomes. Results highlight the needs to meet grandparents’ material needs and call for future research to examine the mechanism that explains the link between material hardship and grandchildren’s outcomes.
    • Mathematical model and simulations of COVID-19 2020 outbreak in New York: Predictions and implications for control measures

      Sinha, Durgesh; Tan, Peiwen; 0000-0001-7749-3710 (2020-05-01)
      The outbreak of the novel coronavirus has resulted in significant morbidity and mortality in the affected 210 countries with 2.4 million people infected and over 163 thousand deaths. The COVID-19 spike protein is effective at binding to human cells, but this COVID-19 backbone differed substantially from other, already known coronaviruses and mostly resembled viruses found in bats and pangolins. To help predict possible dynamics of COVID-19 as well as ways to contain it, this paper develops a mathematical model for the disease, which includes two different infectious routes. The model’s predictions are fitted to data from the outbreak in New York State from the first reported case from March 01, 2020 to April 19, 2020. The containment time and the severity of the outbreaks depend crucially on the contact coefficients and the isolation rate constant. When randomness is added to the model coefficients, the simulations show that the model is sensitive to the scaled contact rate among people and to the isolation rate. The model is analyzed using stability theory for ordinary differential equations and indicates that when using only isolation for control and advising self-recovery, the endemic steady state is locally stable and attractive. After reaching the peak of COVID-19 on April 14, 2020, new infections by the virus would slow down, particularly from the beginning of May at New York State if people keep the isolation. Numerical simulations with parameters estimated from New York State illustrate the analytical results and the model behavior, which may have important implications for the disease containment in other cities. Indeed, the model highlights the importance of isolation of infected individuals and advising self-recovery may be used to assess other control measures. The model is general and may be used to analyze outbreaks in other states of the United States and other countries.
    • Mathematical Modeling Study of the 2020 CoVID-19 Outbreak in the United States

      Sinha, Durgesh; Klahn, Nicholas; 0000-0001-7749-3710 (2020-04-12)
      A mathematical model was developed for the currently evolving COVID-19 outbreak. Data analysis and model fitting using Latin Hypercube Sampling partial Correlation Coefficient Method was used to determine the model’s parameters and basic reproduction numbers. The infectivity values from symptomatic infectious people was 0.118461389 (95% CI [0.1136278, 0.12329497]), asymptomatic transmission was 0.100111427 (95% CI [0.1000297, 0.10019314]), and quarantined transmission was 0.057337278 (95% CI [0.0504738, 0.0642008]). The United states reached its peak basic reproduction number on March 10th where R0=58, but it has since lowered to 1.47 as of April 5th. Also, those in quarantine had contributed the most to the basic reproduction number, with asymptomatic people being second, and regular symptomatic people contributing the least. Our simulations showed that the United States has reached its peak occurred on April 11, 2020 with a total 461,700 number of cases and it will reach on June 12, 2020 where the confirmed case count would reach 1.439 million. As for the longevity of the virus, our prediction shows that it could be under preventive measure within two years by February 10, 2022, would be 14,130.
    • Mathematical Modeling to Estimate the Reproductive Number and the Outbreak Size of COVID-19: The case of India and the World

      Sinha, Durgesh; 0000-0001-7749-3710 (2020-05-04)
      Coronavirus disease (COVID-19) has become a global pandemic with more than 218,000 deaths in 211 different countries around the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for this deadliest disease. This paper describes a mathematical model for India, a country with the second highest population in the world with an extremely high population density of about 464 people per km2. This disease has multiphasic actions and reaction mode and our model SEIAQIm is based on six compartmental groups in the form of susceptible, exposed, infectious, asymptomatic, quarantine, and recovered immune factions. Latin Hypercube Sampling Partial Rank Correlation Coefficient method was used for the data analysis and model fitting. According to our model, India would reach its basic reproduction number R0=0.97 on May 14, 2020 with a total number of 73,800 estimated cases. Further, this study also equates the world's situation using the same model system and predicts by May 7, 2020 with a total number of 3,772,000 estimated confirmed cases. Moreover, the current mathematical model highlights the importance of social distancing as an effective method of containing spread of COVID-19.
    • Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

      Fels Institute for Cancer Research and Molecular Biology (Temple University) (2021-09-09)
      Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with the same potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in mice. Compared with the soluble spike, the I3-01v9 SApNP showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold stronger germinal center reactions in lymph node follicles.
    • Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

      Fels Institute for Cancer Research and Molecular Biology (Temple University) (2021-10-20)
      Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with comparable potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in the mouse model. Compared with the soluble spike, the I3-01v9 SApNP showed sixfold longer retention, fourfold greater presentation on follicular dendritic cell dendrites, and fivefold stronger germinal center reactions in lymph node follicles.