Antibody tests for detecting past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have many uses for public health decision making, but demand has largely come from individual consumers. This review focuses on the individual relevance of antibody tests: their accuracy in detecting prior infection, what past SARS-CoV-2 infection can currently infer about future immunity or possible medical sequelae, and the potential future importance of antibody tests for vaccine selection and medical screening. Given uncertainty about the antibody tests (quality, accuracy level, positive predictive value) and what those tests might indicate immunologically (durability of antibodies and necessity for protection from reinfection), seropositive test results should not be used to inform individual decision making, and antibody testing should remain a tool of public health at this time.
T-cell recognition of peptide/MHC is highly specific and is sensitive to very low levels of agonist peptide, however, it is unclear how this is achieved or regulated. Here we show that clustering class I MHC molecules on the cell surface of B-lymphoblasts enhances their recognition by mouse and human T-cells. We increased clustering of MHC I molecules by two methods, cholesterol depletion and direct crosslinking of a dimerizable MHC construct. Imaging showed that both treatments increased the size and intensity of MHC clusters on the cell surface. Enlarged clusters correlated with enhanced lysis and T-effector function. Enhancements were peptide-specific and greatest at low concentrations of peptide. Clustering MHC I enhanced recognition of both strong and weak agonists but not null peptide. Our results indicate that the lateral organization of MHC I on the cell surface can modulate the sensitivity of T-cell recognition of agonist peptide.
The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.
The Johns Hopkins Center for Health Security is working to analyze and deepen scientific dialogue regarding potential global catastrophic biological risks (GCBRs), in a continuation of its mission to reduce the consequences of epidemics and disasters. Because GCBRs constitute an emerging policy concern and area of practice, we have developed a framework to guide our work. We invited experts from a variety of disciplines to engage with our underlying concepts and assumptions to refine collective thinking on GCBRs and thus advance protections against them.
National investments to facilitate prompt access to safe and effective medical countermeasures (MCMs) (ie, products used to diagnose, prevent, protect from, or treat conditions associated with chemical, biological, radiological, or nuclear threats, or emerging infectious diseases) have little merit if people are not willing to take a recommended MCM during an emergency or inadvertently misuse or miss out on a recommended MCM during an emergency. Informed by the Expert Working Group on MCM Emergency Communication, the Johns Hopkins Center for Health Security developed recommendations for achieving desired public health outcomes through improved MCM communication based on a review of model practices in risk communication, crisis communication, and public warnings; detailed analysis of recent health crises involving MCMs; and development of a scenario depicting future MCM communication dilemmas. The public's topics of concern, emotional requirements, capacity for processing information, and health needs will evolve as an emergency unfolds, from a pre-event period of routine conditions, to a crisis state, to a post-event period of reflection. Thus, MCM communication by public health authorities requires a phased approach that spans from building up a reputation as a trusted steward of MCMs between crises to developing recovery-focused messages about applying newly acquired data about MCM safety, efficacy, and accessibility to improve future situations.
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