Antigenic waves of virus-immune coevolution.
06 Jul 2021-Proceedings of the National Academy of Sciences of the United States of America (Proceedings of the National Academy of Sciences)-Vol. 118, Iss: 27, pp 2103398118
TL;DR: In this article, the authors present a mathematical theory 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.
Abstract: The evolution of many microbes and pathogens, including circulating viruses such as seasonal influenza, is driven by immune pressure from the host population. In turn, the immune systems of infected populations get updated, chasing viruses even farther away. Quantitatively understanding how these dynamics result in observed patterns of rapid pathogen and immune adaptation is instrumental to epidemiological and evolutionary forecasting. Here we present a mathematical theory 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. We show the emergence of an antigenic wave that is pushed forward and canalized by cross-reactivity. We obtain analytical results for shape, speed, and angular diffusion of the wave. In particular, we show that viral-immune coevolution generates an emergent timescale, the persistence time of the wave's direction in antigenic space, which can be much longer than the coalescence time of the viral population. We compare these dynamics to the observed antigenic turnover of influenza strains, and we discuss how the dimensionality of antigenic space impacts the predictability of the evolutionary dynamics. Our results provide a concrete and tractable framework to describe pathogen-host coevolution.
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TL;DR: A model by which sarbecoviruses are activated for fusion competency is provided and a framework for understanding the interplay between humoral immunity and the molecular evolution of the SARS-CoV-2 Spike is offered.
Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic demonstrates the threat posed by novel coronaviruses to human health. Coronaviruses share a highly conserved cell entry mechanism mediated by the spike protein, the sole product of the S gene. ABSTRACT The ongoing coronavirus disease 2019 (COVID-19) pandemic demonstrates the threat posed by novel coronaviruses to human health. Coronaviruses share a highly conserved cell entry mechanism mediated by the spike protein, the sole product of the S gene. The structural dynamics by which the spike protein orchestrates infection illuminate how antibodies neutralize virions and how S mutations contribute to viral fitness. Here, we review the process by which spike engages its proteinaceous receptor, angiotensin converting enzyme 2 (ACE2), and how host proteases prime and subsequently enable efficient membrane fusion between virions and target cells. We highlight mutations common among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern and discuss implications for cell entry. Ultimately, we provide a model by which sarbecoviruses are activated for fusion competency and offer a framework for understanding the interplay between humoral immunity and the molecular evolution of the SARS-CoV-2 Spike. In particular, we emphasize the relevance of the Canyon Hypothesis (M. G. Rossmann, J Biol Chem 264:14587–14590, 1989) for understanding evolutionary trajectories of viral entry proteins during sustained intraspecies transmission of a novel viral pathogen.
11 citations
TL;DR: It is shown that for the first time from the beginning of pandemic COVID-19 some countries reached collective immunity, however, the epidemic continues because of the emergence of new variant BA.2 with a larger immunity escape or disease transmission rate than the previous BA.1 variant.
Abstract: We develop a new data-driven immuno-epidemiological model with distributed infectivity, recovery and death rates determined from the epidemiological, clinical and experimental data. Immunity in the population is taken into account through the time-dependent number of vaccinated people with different numbers of doses and through the acquired immunity for recovered individuals. The model is validated with the available data. We show that for the first time from the beginning of pandemic COVID-19 some countries reached collective immunity. However, the epidemic continues because of the emergence of new variant BA.2 with a larger immunity escape or disease transmission rate than the previous BA.1 variant. Large epidemic outbreaks can be expected several months later due to immunity waning. These outbreaks can be restrained by an intensive booster vaccination.
9 citations
TL;DR: It is shown that when the pathogen does not have to cross a fitness valley for immune escape to occur, immunocompromised individuals have no qualitative effect on antigenic evolution, and better global health equality may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.
Abstract: The apparent lack of antigenic evolution by the Delta variant (B.1.617.2) of SARS-CoV-2 during the COVID-19 pandemic is puzzling. The combination of increasing immune pressure due to the rollout of vaccines and a relatively high number of infections following the relaxation of non-pharmaceutical interventions should have created perfect conditions for immune escape variants to evolve from the Delta lineage. Instead, the Omicron variant (B.1.1.529), which is hypothesised to have evolved in an immunocompromised individual, is the first major variant to exhibit significant immune escape following vaccination programmes and is set to become globally dominant in 2022. Here, we use a simple mathematical model to explore possible reasons why the Delta lineage did not exhibit antigenic evolution and to understand how and when immunocompromised individuals affect the emergence of immune escape variants. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur, immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level, then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.
7 citations
TL;DR: The theory recapitulates known modes of the B cell response, predicts the empirical form of the distribution of clone sizes, and rationalizes as a trade-off between metabolic and immune costs the antigenic imprinting effects that limit the efficacy of vaccines
Abstract: Significance Humoral immunity relies on the mutation and selection of B cells to better recognize pathogens. This affinity maturation process produces cells with diverse recognition capabilities. Examining optimal immune strategies that maximize the long-term immune coverage at a minimal metabolic cost, we show when the immune system should mount a de novo response rather than rely on existing memory cells. Our theory recapitulates known modes of the B cell response, predicts the empirical form of the distribution of clone sizes, and rationalizes as a trade-off between metabolic and immune costs the antigenic imprinting effects that limit the efficacy of vaccines (original antigenic sin). Our predictions provide a framework to interpret experimental results that could be used to inform vaccination strategies. In order to target threatening pathogens, the adaptive immune system performs a continuous reorganization of its lymphocyte repertoire. Following an immune challenge, the B cell repertoire can evolve cells of increased specificity for the encountered strain. This process of affinity maturation generates a memory pool whose diversity and size remain difficult to predict. We assume that the immune system follows a strategy that maximizes the long-term immune coverage and minimizes the short-term metabolic costs associated with affinity maturation. This strategy is defined as an optimal decision process on a finite dimensional phenotypic space, where a preexisting population of cells is sequentially challenged with a neutrally evolving strain. We show that the low specificity and high diversity of memory B cells—a key experimental result—can be explained as a strategy to protect against pathogens that evolve fast enough to escape highly potent but narrow memory. This plasticity of the repertoire drives the emergence of distinct regimes for the size and diversity of the memory pool, depending on the density of de novo responding cells and on the mutation rate of the strain. The model predicts power-law distributions of clonotype sizes observed in data and rationalizes antigenic imprinting as a strategy to minimize metabolic costs while keeping good immune protection against future strains.
6 citations
13 Jan 2022
TL;DR: In this article , the authors used a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis.
Abstract: Abstract Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution. Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2. Lay Summary We study the role that immunocompromised individuals may play in the evolution of novel variants of the coronavirus responsible for the COVID-19 pandemic. We show that immunocompromised hosts can be crucial for the evolution of immune escape variants. Targeted treatment and surveillance may therefore prevent the emergence of new variants.
4 citations
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TL;DR: The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003 and offers a route to predicting the relative success of emerging strains.
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1,606 citations