Eradicating infectious disease using weakly transmissible vaccines.

Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution.

Coevolutionary immune system dynamics driving pathogen speciation.

We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction.

Measuring and modeling behavioral decision dynamics in collective evacuation.

Identifying and quantifying factors influencing human decision making remains an outstanding challenge, impacting the performance and predictability of social and technological systems. In many cases, system failures are traced to human factors including congestion, overload, miscommunication, and delays. Here we report results of a behavioral network science experiment, targeting decision making in a natural disaster.

Population-expression models of immune response.

The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection.

Diversity of T-cell responses.

Using a dynamic model we study the adaptive immune response to a sequence of two infections. We incorporate lymphocyte diversity by modeling populations as continuous distributions in a multi-dimensional space. As expected, memory cells generated by the primary infection invoke a rapid response when the secondary infection is identical (homologous).

On the role of CD8 T cells in the control of persistent infections.

The control of pathogen density during infections is typically assumed to be the result of a combination of resource limitation (loss of target cells that the pathogen can infect), innate immunity, and specific immunity. The contributions of these factors have been considered in acute infections, which are characterized by having a short duration. What controls the pathogen during persistent infections is less clear, and is complicated by two factors.

Vaccination by delayed treatment of infection.

Two medical interventions allow us to combat infectious diseases: vaccination which can be administered well in advance of exposure, and antimicrobials which are most often administered contemporaneously with exposure. In this paper we show how they can, in principle, be combined - with infection followed by treatment being used as a form of vaccination. We use mathematical models to examine how appropriately administered antimicrobial treatment following natural infection can be used to reduce the pathology caused by the infection, and also generate long-lasting immunological memory to the pathogen.

The suppression of immune system disorders by passive attrition.

Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases and allergies. This is one of many fundamental fitness tradeoffs associated with immune system architecture. The immune system attacks pathogens, but also may (inappropriately) attack the host.

Robustness and fragility in immunosenescence.

We construct a model to study tradeoffs associated with aging in the adaptive immune system, focusing on cumulative effects of replacing naive cells with memory cells. Binding affinities are characterized by a stochastic shape space model. System loss arising from an individual infection is associated with disease severity, as measured by the total antigen population over the course of an infection.