Vaccin contre la poliomyélite

Le vaccin contre la poliomyélite a pour but de prévenir une maladie causée par un virus appartenant à un sérotype de poliovirus. L'efficacité de ce vaccin destiné à prévenir la poliomyélite est élevée et ses effets secondaires sont le plus souvent sans gravité. Il fait partie des vaccins recommandés tout au long de la vie. La poliomyélite est due à un virus parmi les 3 sérotypes de poliovirus. Il s'agit d'une maladie touchant le tractus gastro-intestinal et pouvant atteindre les tissus nerveux. La gravité est liée à la survenue d'une forme paralytique, de l’ordre de 1 pour infections chez le petit enfant et de 1 pour 75 infections chez l’adulte. Un vaccin est développé par Jonas Salk en 1955. Parallèlement, en collaboration, Mikhaïl Tchoumakov en URSS de 1958-1959 a organisé la première production massive et les tests cliniques du vaccin contre la poliomyélite (VVACP) créé à partir de virus vivants atténuées développés par Albert Sabin. Cela fait de l’Union soviétique le premier pays à produire, breveter et largement utiliser ce vaccin très efficace qui a pratiquement éliminé la poliomyélite du pays après seulement quelques années d'utilisation. Un vaccin est dévéloppé quasiment simultanément à l'Institut Pasteur par le Professeur Pierre Lepine. Albert Bruce Sabin Invente le vaccin antipoliomyélitique oral dans les années 1960, quelques années après la mise au point du vaccin inactivé. Sabin a refusé de breveter son vaccin, renonçant à toute exploitation commerciale par les industries pharmaceutiques, afin que le bas prix garantisse une diffusion plus large du traitement et puisse être accessible à toutes les populations mondiales mêmes les plus pauvres. Depuis 2019, grâce au soutien de la Fondation Bill-et-Melinda-Gates, un vaccin très bon marché est produit par Univercells pour les pays en voie de développement (Pakistan, Afghanistan, Nigéria). De fausses rumeurs dissuadent souvent les populations concernées de se faire vacciner. Le vaccin contre la poliomyélite existe sous forme inactivée ou atténuée.

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

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

Clara Galan Navarro

EPFL2017