Model-informed optimal allocation of limited resources to mitigate infectious disease outbreaks in societies at war.

Infectious diseases thrive in war-torn societies. The recent sharp increase in human conflict and war thus requires the development of disease mitigation tools that account for the specifics of war, such as the scarcity of important public health resources. We developed a compartmental, differential equation-based disease model that considers key social, war and disease mechanisms, such as gender homophily and the replacement of soldiers.

Learning from the COVID-19 pandemic: A systematic review of mathematical vaccine prioritization models.

As the world becomes ever more connected, the chance of pandemics increases as well. The recent COVID-19 pandemic and the concurrent global mass vaccine roll-out provides an ideal setting to learn from and refine our understanding of infectious disease models for better future preparedness. In this review, we systematically analyze and categorize mathematical models that have been developed to design optimal vaccine prioritization strategies of an initially limited vaccine.

Diffusion and Chemical Degradation of Vitamin B6 in Chickpeas ( L.) during Hydrothermal Treatments: A Kinetic Approach.

Chickpeas are more sustainable than other food systems and have high a nutritional value, especially regarding their vitamin composition. One of the main vitamins in chickpeas is vitamin B6, which is very important for several human metabolic functions. Since chickpeas are consumed after cooking, our goal was to better understand the role of leaching (diffusion) and thermal degradation of vitamin B6 in chickpeas during hydrothermal processing.

Canalization reduces the nonlinearity of regulation in biological networks.

Biological networks, such as gene regulatory networks, possess desirable properties. They are more robust and controllable than random networks. This motivates the search for structural and dynamical features that evolution has incorporated into biological networks.

Learning from the COVID-19 pandemic: a systematic review of mathematical vaccine prioritization models.

As the world becomes ever more connected, the chance of pandemics increases as well. The recent COVID-19 pandemic and the concurrent global mass vaccine roll-out provides an ideal setting to learn from and refine our understanding of infectious disease models for better future preparedness. In this review, we systematically analyze and categorize mathematical models that have been developed to design optimal vaccine prioritization strategies of an initially limited vaccine.

Modular control of Boolean network models.

The concept of control is crucial for effectively understanding and applying biological network models. Key structural features relate to control functions through gene regulation, signaling, or metabolic mechanisms, and computational models need to encode these. Applications often focus on model-based control, such as in biomedicine or metabolic engineering.

A meta-analysis of Boolean network models reveals design principles of gene regulatory networks.

Gene regulatory networks (GRNs) play a central role in cellular decision-making. Understanding their structure and how it impacts their dynamics constitutes thus a fundamental biological question. GRNs are frequently modeled as Boolean networks, which are intuitive, simple to describe, and can yield qualitative results even when data are sparse.

Modularity of biological systems: a link between structure and function.

This paper addresses two topics in systems biology, the hypothesis that biological systems are modular and the problem of relating structure and function of biological systems. The focus here is on gene regulatory networks, represented by Boolean network models, a commonly used tool. Most of the research on gene regulatory network modularity has focused on network structure, typically represented through either directed or undirected graphs.

Modularity of biological systems: a link between structure and function.

This paper addresses two topics in systems biology, the hypothesis that biological systems are modular and the problem of relating structure and function of biological systems. The focus here is on gene regulatory networks, represented by Boolean network models, a commonly used tool. Most of the research on gene regulatory network modularity has focused on network structure, typically represented through either directed or undirected graphs.

Projecting social contact matrices to populations stratified by binary attributes with known homophily.

Contact networks are heterogeneous. People with similar characteristics are more likely to interact, a phenomenon called assortative mixing or homophily. Empirical age-stratified social contact matrices have been derived by extensive survey work.

Ethnic homophily affects vaccine prioritization strategies.

People are more likely to interact with other people of their ethnicity-a phenomenon known as ethnic homophily. In the United States, people of color are known to hold proportionately more high-contact jobs and are thus more at risk of virus infection. At the same time, these ethnic groups are on average younger than the rest of the population.

Effect of homophily and correlation of beliefs on COVID-19 and general infectious disease outbreaks.

Contact between people with similar opinions and characteristics occurs at a higher rate than among other people, a phenomenon known as homophily. The presence of clusters of unvaccinated people has been associated with increased incidence of infectious disease outbreaks despite high population-wide vaccination rates. The epidemiological consequences of homophily regarding other beliefs as well as correlations among beliefs or circumstances are poorly understood, however.

Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.

The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement.

Evaluation of the United States COVID-19 vaccine allocation strategy.

Background: Anticipating an initial shortage of vaccines for COVID-19, the Centers for Disease Control (CDC) in the United States developed priority vaccine allocations for specific demographic groups in the population. This study evaluates the performance of the CDC vaccine allocation strategy with respect to multiple potentially competing vaccination goals (minimizing mortality, cases, infections, and years of life lost (YLL)), under the same framework as the CDC allocation: four priority vaccination groups and population demographics stratified by age, comorbidities, occupation and living condition (congested or non-congested).

Methods And Findings: We developed a compartmental disease model that incorporates key elements of the current pandemic including age-varying susceptibility to infection, age-varying clinical fraction, an active case-count dependent social distancing level, and time-varying infectivity (accounting for the emergence of more infectious virus strains).

A model-based evaluation of the efficacy of COVID-19 social distancing, testing and hospital triage policies.

A stochastic compartmental network model of SARS-CoV-2 spread explores the simultaneous effects of policy choices in three domains: social distancing, hospital triaging, and testing. Considering policy domains together provides insight into how different policy decisions interact. The model incorporates important characteristics of COVID-19, the disease caused by SARS-CoV-2, such as heterogeneous risk factors and asymptomatic transmission, and enables a reliable qualitative comparison of policy choices despite the current uncertainty in key virus and disease parameters.

Phylogenetic Cluster Analysis Identifies Virological and Behavioral Drivers of Human Immunodeficiency Virus Transmission in Men Who Have Sex With Men.

Background: Identifying local outbreaks and their drivers is a key step toward curbing human immunodeficiency virus (HIV) transmission and potentially achieving HIV elimination. Such outbreaks can be identified as transmission clusters extracted from phylogenetic trees constructed of densely sampled viral sequences. In this study, we combined phylogenetic transmission clusters with extensive data on virological suppression and behavioral risk of cluster members to quantify the drivers of ongoing transmission over 10 years.

Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells.

Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21 memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection.

Correlates of broadly neutralizing antibody development.

Purpose Of Review: Broadly neutralizing antibodies (bnAbs) are considered a key component of an effective HIV-1 vaccine, but despite intensive efforts, induction of bnAbs by vaccination has thus far not been possible. Potent bnAb activity is rare in natural infection and a deeper understanding of factors that promote or limit bnAb evolution is critical to guide bnAb vaccine development. This review reflects on recent key discoveries on correlates of bnAb development and discusses what further insights are needed to move forward.

Importance of routine viral load monitoring: higher levels of resistance at ART failure in Uganda and Lesotho compared with Switzerland.

Objectives: Emerging resistance to antiretroviral drugs may jeopardize the achievements of improved access to ART. We compared the prevalence of different resistance mutations in HIV-infected adults with virological failure in a cohort with regular routine viral load (VL) monitoring (Switzerland) and cohorts with limited access to VL testing (Uganda and Lesotho).

Methods: We considered individuals who had genotypic resistance testing (GRT) upon virological failure (≥1000 copies/mL) and were on ART consisting of at least one NNRTI and two NRTIs.

Inferring the age difference in HIV transmission pairs by applying phylogenetic methods on the HIV transmission network of the Swiss HIV Cohort Study.

Age-mixing patterns are of key importance for understanding the dynamics of human immunodeficiency virus (HIV)-epidemics and target public health interventions. We use the densely sampled Swiss HIV Cohort Study (SHCS) resistance database to study the age difference at infection in HIV transmission pairs using phylogenetic methods. In addition, we investigate whether the mean age difference of pairs in the phylogenetic tree is influenced by sampling as well as by additional distance thresholds for including pairs.

Tracing HIV-1 strains that imprint broadly neutralizing antibody responses.

Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans.

Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity.

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses.

Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage.

Broadly neutralizing antibodies (bnAbs) to HIV-1 can evolve after years of an iterative process of virus escape and antibody adaptation that HIV-1 vaccine design seeks to mimic. To enable this, properties that render HIV-1 envelopes (Env) capable of eliciting bnAb responses need to be defined. Here, we followed the evolution of the V2 apex directed bnAb lineage VRC26 in the HIV-1 subtype C superinfected donor CAP256 to investigate the phenotypic changes of the virus populations circulating before and during the early phases of bnAb induction.

Development of a high-throughput bead based assay system to measure HIV-1 specific immune signatures in clinical samples.

The monitoring and assessment of a broadly neutralizing antibody (bnAb) based HIV-1 vaccine require detailed measurements of HIV-1 binding antibody responses to support the detection of correlates of protection. Here we describe the development of a flexible, high-throughput microsphere based multiplex assay system that allows monitoring complex binding antibody signatures. Studying a panel of 13 HIV-1 antigens in a parallel assessment of different IgG subclasses (IgG1, IgG2 and IgG3) we demonstrate the potential of our strategy.

Assessing the danger of self-sustained HIV epidemics in heterosexuals by population based phylogenetic cluster analysis.

Assessing the danger of transition of HIV transmission from a concentrated to a generalized epidemic is of major importance for public health. In this study, we develop a phylogeny-based statistical approach to address this question. As a case study, we use this to investigate the trends and determinants of HIV transmission among Swiss heterosexuals.