Biophysical and Biochemical Characterization of the Receptor Binding Domain of SARS-CoV-2 Variants.

The newly emerging SARS-CoV-2 variants are potential threat and posing new challenges for medical intervention due to high transmissibility and escaping neutralizing antibody (NAb) responses. Many of these variants have mutations in the receptor binding domain (RBD) of SARS-CoV-2 spike protein that interacts with the host cell receptor. Rapid mutation in the RBD through natural selection to improve affinity for host receptor and antibody pressure from vaccinated or infected individual will greatly impact the presently adopted strategies for developing interventions. Understanding the nature of mutations and how they impact the biophysical, biochemical and immunological properties of the RBD will help immensely to improve the intervention strategies. To understand the impact of mutation on the protease sensitivity, thermal stability, affinity for the receptor and immune response, we prepared several mutants of soluble RBD that belong to the variants of concern (VoCs) and interest (VoIs) and characterize them. Our results show that the mutations do not impact the overall structure of the RBD. However, the mutants showed increase in the thermal melting point, few mutants were more sensitive to protease degradation, most of them have enhanced affinity for ACE2 and some of them induced better immune response compared to the parental RBD.

Designing and characterization of a SARS-CoV-2 immunogen with receptor binding motif grafted on a protein scaffold: An epitope-focused vaccine approach.

The COVID-19 pandemic caused by SARS-CoV-2 has a significant burden on the economy and healthcare around the world. Vaccines are the most effective tools to fight infectious diseases by containing the spread of the disease. The current vaccines against SARS-CoV-2 are mostly based on the spike protein of SARS-CoV-2, which is large and has many immune-dominant non-neutralizing epitopes that may effectively skew the antibody response towards non-neutralizing antibodies. Here, we have explored the possibility of immune-focusing the receptor binding motif (RBM) of the spike protein of SARS-CoV-2 that induces mostly neutralizing antibodies in natural infection or in vacinees. The result shows that the scaffolded RBM can bind to Angiotensin Converting Enzyme 2 (ACE2) although with low affinity and induces a strong antibody response in mice. The immunized sera can bind both, the receptor binding domain (RBD) and the spike protein, which holds the RBM in its natural context. Sera from the immunized mice showed robust interferon γ response but poor neutralization of SARS-CoV-2 suggesting presence of a predominant T cell epitope on scaffolded RBM. Together, we provide a strategy for inducing strong antigenic T cell response which could be exploited further for future vaccine designing and development against SARS-CoV-2 infection.

Coordinating a local response to a national tragedy: community mental health in Washington, DC after the Pentagon attack.

Concerns about the potential long-term mental health needs created by the Pentagon attack on September 11, 2001 and subsequent events raised concerns about the local system's capacity to respond. These concerns led to the establishment of the Mental Health Community Response Coalition, which has met regularly since September 23. The primary purpose of the Mental Health Community Response Coalition has been to provide vital opportunities for networking and information exchange between military service providers, the American Red Cross, local mental health agencies, and others. Prevention of duplication and overlap of services among different agencies has also been an important focus of the group. This paper outlines the structure of the coalition and lessons learned for the development of a coordinated mental health effort in response to a community crisis.

The integration of mental and behavioral health into disaster preparedness, response, and recovery.

The close interplay between mental health and physical health makes it critical to integrate mental and behavioral health considerations into all aspects of public health and medical disaster management. Therefore, the National Biodefense Science Board (NBSB) convened the Disaster Mental Health Subcommittee to assess the progress of the US Department of Health and Human Services (HHS) in integrating mental and behavioral health into disaster and emergency preparedness and response activities. One vital opportunity to improve integration is the development of clear and directive national policy to firmly establish the role of mental and behavioral health as part of a unified public health and medical response to disasters. Integration of mental and behavioral health into disaster preparedness, response, and recovery requires it to be incorporated in assessments and services, addressed in education and training, and founded on and advanced through research. Integration must be supported in underlying policies and administration with clear lines of responsibility for formulating and implementing policy and practice.

The H1N1 crisis: a case study of the integration of mental and behavioral health in public health crises.

In substantial numbers of affected populations, disasters adversely affect well-being and influence the development of emotional problems and dysfunctional behaviors. Nowhere is the integration of mental and behavioral health into broader public health and medical preparedness and response activities more crucial than in disasters such as the 2009-2010 H1N1 influenza pandemic. The National Biodefense Science Board, recognizing that the mental and behavioral health responses to H1N1 were vital to preserving safety and health for the country, requested that the Disaster Mental Health Subcommittee recommend actions for public health officials to prevent and mitigate adverse behavioral health outcomes during the H1N1 pandemic. The subcommittee's recommendations emphasized vulnerable populations and concentrated on interventions, education and training, and communication and messaging. The subcommittee's H1N1 activities and recommendations provide an approach and template for identifying and addressing future efforts related to newly emerging public health and medical emergencies. The many emotional and behavioral health implications of the crisis and the importance of psychological factors in determining the behavior of members of the public argue for a programmatic integration of behavioral health and science expertise in a comprehensive public health response.