Bulletin of the American Physical Society
2023 APS March Meeting
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session Q13: Delbruck Prize SymposiumInvited Session Undergrad Friendly
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Sponsoring Units: DBIO Chair: Joshua Shaevitz, Princeton University Room: Room 238 |
Wednesday, March 8, 2023 3:00PM - 3:36PM |
Q13.00001: Max Delbruck Prize in Biological Physics: Viruses, Immunity and Vaccines Invited Speaker: Arup K Chakraborty Infectious disease-causing pathogens have plagued humanity since antiquity, and the COVID-19 pandemic has been a vivid reminder of this perpetual existential threat. Vaccination has saved more lives than any other medical procedure, and indeed, effective vaccines have helped control the COVID-19 pandemic. However, we do not have effective vaccines against rapidly mutating viruses, such as HIV; nor do we have a universal vaccine against seasonal variants of influenza or SARS-CoV-2 variants that continue to evolve. The ability to develop effective universal vaccines that protect us from variant strains of mutable viruses will help create a more pandemic-resilient world. I will describe how by bringing together approaches from statistical physics, virology and immunology, progress is being made to address this challenge. In particular, I will focus on approaches that aim to design vaccines and immunization strategies that elicit antibodies that can protect against diverse mutant strains. As I hope to show, this is a problem at the intersection of statistical physics, evolutionary biology, immunology, and vaccine development. The application of fundamental concepts to HIV, influenza and SARS-CoV-2 vaccines will be discussed. |
Wednesday, March 8, 2023 3:36PM - 4:12PM |
Q13.00002: Maturation, selection and response in immune repertoires Invited Speaker: Aleksandra M Walczak One of the feats of adaptive immunity is its ability to recognize foreign pathogens while sparing the self. During maturation in the thymus, T cells are selected through the binding properties of their antigen-specific T-cell receptor (TCR), through the elimination of both weakly (positive selection) and strongly (negative selection) self-reactive receptors. I will present the results of a search for eliminated motifs and how they can be interpreted from a quorum sensing perspective. At the population scales, the repertoires of many hosts drive the evolution of viruses. I will present a framework of coevolution between immune systems and viruses in a finite-dimensional antigenic space, which describes the cross-reactivity of viral strains and immune systems primed by previous infections. I will show the emergence of an antigenic wave that is pushed forward and canalized by cross-reactivity. I will discuss the results in the context of the observed antigenic turnover of influenza strains, and we discuss how the dimensionality of antigenic space impacts the predictability of the evolutionary dynamics. |
Wednesday, March 8, 2023 4:12PM - 4:48PM |
Q13.00003: Affinity maturation of antibodies targeting HIV spikes Invited Speaker: Mehran Kardar Affinity maturation (AM) is the process through which the immune system evolves antibodies (Abs) which efficiently bind to antigens (Ags), e.g. to spikes on the surface of a virus. This process involves competition between B-cells: those that ingest more Ags receive signals (from T helper cells) to replicate and mutate for another round of competition. Modeling this process, we find that the affinity of the resulting Abs is a non-monotonic function of the target (e.g. viral spike) density, with the strongest binding at an intermediate density (set by the two-arm structure of the antibody). We argue that, to evade the immune system, most viruses evolve high spike densities (SDs). An exception is HIV whose SD is two orders of magnitude lower than other viruses. However, HIV also interferes with AM by depleting T helper cells, a key component of Ab evolution. We find that T helper cell depletion results in high affinity antibodies when SD is high, but not if SD is low. This special feature of HIV infection may have led to the evolution of a low SD to avoid potent immune responses early on in infection. Our modeling also provides guides for design of vaccination strategies against rapidly mutating viruses. |
Wednesday, March 8, 2023 4:48PM - 5:24PM |
Q13.00004: Clonal and cellular dynamics of the antibody response Invited Speaker: Gabriel Victora The average affinity of specific antibodies increases dramatically over the course of an immune response. This increase is the result of a Darwinian process in which B lymphocytes undergo iterative cycles of random hypermutation of their immunoglobulin genes, followed by selective proliferation of clones bearing affinity-enhancing mutations. This evolutionary process takes place in highly dynamic microanatomical structures known as germinal centers, which arise within secondary lymphoid organs upon infection or immunization. Our work combines intravital multiphoton microscopy with mouse genetics to study how the dynamics of B and T lymphocytes within germinal centers shapes the evolution of the high-affinity antibodies that are crucial to protection from infectious disease. |
Wednesday, March 8, 2023 5:24PM - 6:00PM |
Q13.00005: TBD Invited Speaker: Jay T Groves
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