Maladie infectieuse émergente

Une maladie infectieuse émergente est une maladie causée par un agent infectieux (d'origine bactérienne, virale, parasitaire, fongique ou un prion) ou présumée telle, inattendue, affectant l'humain ou l'animal ou les deux. Elle est inattendue parce qu'elle est réellement nouvelle (nouvel agent infectieux), ou parce que son identification est récente (nouvelle capacité à faire le diagnostic), ou parce que son agent infectieux s'est modifié en acquérant de nouvelles caractéristiques (nouvelle expression clinique ou épidémiologique, gravité modifiée, résistances aux traitements, etc.), ou parce qu'elle a été oubliée et que sa réapparition est inattendue (réémergence). Au , après des décennies pendant lesquelles on a cru fermement à la disparition prochaine des maladies infectieuses du fait de la découverte de vaccins et médicaments très efficaces soutenus par des politiques extensives d'amélioration de l'hygiène individuelle et collective, le dernier quart du siècle a au contraire dû adm

Evaluation of oxidation-sensitive polymersomes as vaccine nanocarriers to enhance humoral responses against arenavirus envelope glycoproteins

Clara Galan Navarro

Vaccines currently represent one of the most effective means to control and prevent infectious diseases affecting humans and animals and have dramatically improved public health, quality of life, and life expectancy. Over the last years several conceptual and technological advances in the field of bioengineering and immunology have allowed the development of new vaccines designs. Expanding novel domains such as structural biology, human monoclonal antibody isolation, high throughput sequencing, and design of new nanocarrier delivery platforms have changed the landscape of vaccinology. These new vaccine formulations allow the design of tailor-made antigens and particulate vehicles which allow better and fine-tuned protective immune responses against known and newly emerging pathogens. Over the past decades emerging human pathogens with the potential to cause severe epidemics have become a major public health problem. The last Ebola and Zika virus epidemics demonstrated in a dramatic manner that there is an urgent need to develop prophylactic and therapeutic approaches against pathogenic emerging viruses. Most successful vaccines rely on attenuated live microorganisms to induce protective immunity. However, changed demographics and associated safety concerns makes the development of a safer alternative a priority. Subunit vaccines composed of microbial components and proteins have emerged as a suitable alternative, however they are generally less immunogenic. To address this problematic our laboratory works on the development of immunization platforms which allow 1) the development of safe recombinant subunit vaccines and 2) the rapid generation of specific monoclonal antibodies using biosynthetic immunogens without the need for prior isolation and culture of the agent. The approach evaluated in the present studies is based on a novel polymersome (PS) platform serving as nanocarrier for efficient antigen delivery and the induction of humoral immunity. The potential of PS was assessed in the context of two important human emerging pathogens form the arenavirus family that cause severe hemorrhagic fevers and of which there are neither FDA-approved vaccines not prophylactic treatments: Lassa virus (LASV), endemic in Western Africa, and Machupo virus (MACV), the causative agent of Bolivian hemorrhagic fever. In a first part, we evaluated the PS platformâs capacity to enhance humoral immunity against the envelope glycoprotein 1 of LASV, (LASV GP1) that is notorious for its weak immunogenicity and poor antibody response. Immunization of mice with adjuvanted PS (LASV GP1) enhanced the quality of the humoral response to LASV GP1, eliciting antibodies with higher binding affinity to virion GP1, increased levels of polyfunctional anti-viral CD4 T cells, and the frequency of IgG-secreting B cells. PS (LASV GP1) elicited a more diverse epitope repertoire of anti-viral IgG. In a second part, we employed the PS platform in combination with single cell B cell sorting and cloning of recombinant IgG to generate a first set of species-specific mAbs against MACV. These new mAbs show exquisite specificity and negligible cross-reactivity to closely related arenaviruses in relevant techniques making them a unique and powerful tool for research and diagnostics purposes.

EPFL2017

Infectious Disease Containment Based on a Wireless Sensor System

Marcel Salathé, Xiao Sun

Infectious diseases pose a serious threat to public health due to its high infectivity and potentially high mortality. One of the most effective ways to protect people from being infected by these diseases is through vaccination. However, due to various resource constraints, vaccinating all the people in a community is not practical. Therefore, targeted vaccination, which vaccinates a small group of people, is an alternative approach to contain infectious diseases. Since many infectious diseases spread among people by droplet transmission within a certain range, we deploy a wireless sensor system in a high school to collect contacts happened within the disease transmission distance. Based on the collected traces, a graph is constructed to model the disease propagation, and a new metric (called connectivity centrality) is presented to find the important nodes in the constructed graph for disease containment. Connectivity centrality considers both a node's local and global effect to measure its importance in disease propagation. Centrality based algorithms are presented and further enhanced by exploiting the information of the known infected nodes, which can be detected during targeted vaccination. Simulation results show that our algorithms can effectively contain infectious diseases and outperform other schemes under various conditions.

Ieee-Inst Electrical Electronics Engineers Inc2016

A high-resolution human contact network for infectious disease transmission

Marcel Salathé

The most frequent infectious diseases in humans--and those with the highest potential for rapid pandemic spread--are usually transmitted via droplets during close proximity interactions (CPIs). Despite the importance of this transmission route, very little is known about the dynamic patterns of CPIs. Using wireless sensor network technology, we obtained high-resolution data of CPIs during a typical day at an American high school, permitting the reconstruction of the social network relevant for infectious disease transmission. At 94% coverage, we collected 762,868 CPIs at a maximal distance of 3 m among 788 individuals. The data revealed a high-density network with typical small-world properties and a relatively homogeneous distribution of both interaction time and interaction partners among subjects. Computer simulations of the spread of an influenza-like disease on the weighted contact graph are in good agreement with absentee data during the most recent influenza season. Analysis of targeted immunization strategies suggested that contact network data are required to design strategies that are significantly more effective than random immunization. Immunization strategies based on contact network data were most effective at high vaccination coverage.

2010

Evaluation of oxidation-sensitive polymersomes as vaccine nanocarriers to enhance humoral responses against arenavirus envelope glycoproteins

Clara Galan Navarro

EPFL2017