Emergence - Emergence

Development of an innovative sub-unit vaccine against toxoplasmosis – NANOTOXO

Development of a sub-unit vaccine against toxoplasmosis based on nanoparticles

A life vaccine is on the market however it has numerous drawbacks: very poor stability at room temperature, low efficacy and potential risk of infection by the parasites. The development of a sub-unit vaccine based on nanoparticles is necessary to lower toxoplasma infection burden.

Development of a nanoparticulate mucosal vaccine against toxoplasma infection

Toxoplasmosis is a parasitic disease affecting up to 50% of the human population in western europe. Human is contaminated by eating infected meat. Deleting the animal reservoir will lead to decrease the prevalence of the disease and increase the production of meat livestock, by limiting spontaneous abortion from infected animals. The main objective of the NANOTOXO project is to develop and improve a sub-unit vaccine without living parasite, based on nanoparticles, in order to increase the efficacy of the vaccine, compared to the existing ones, to improve the stability of the vaccine and to bypass the underlying risks caused by the use of living parasites for vaccine. It will be used to vaccine livestock animals to gain in productivity and limit the transmission to human beings.

Nanoparticles used in the NANOTOXO project are made of starch and lipids. The nanoparticles will be coupled to Toxoplasma gondii antigens to generate our vaccine formulation. The formulation will be optimised in term of antigen binding and stability. Studies of the vaccine will be performed in mice in order to elicit an immune response protective against Toxoplasma gondii infection.

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PATENT 1. Betbeder D., Dimier-Poisson I. Ducourneau C.
Pharmaceutical composition for its use in the preventive treatment of infections caused by an intra-cellular pathogen, more particularly Toxoplasma gondii.
European patent N°: 12370002.3-2406 date of filing: 17.09.12

Congenital toxoplasmosis is of considerable economic importance in the livestock industry, because it is one of the principal causes of fetal death, stillbirths and abortion (1 million in Europe every year) in sheep and goat. Primary Toxoplasma infection leads to an immune response that confers lifelong protection against reinfection and against the congenital transmission of toxoplasmosis. Therefore, it should be possible to develop a safe and effective vaccine against acquired and congenital toxoplasmosis.

Presently only one vaccine, based on live attenuated Toxoplasma tachyzoites, has been licensed. However, the possibility exists that it might at some point revert to a pathogenic form, which makes it a poor vaccine candidate for humans.

Moreover, this vaccine is expensive, requires a cold storage for its delivery, causes side effects, is difficult to manufacture and has a short shelf life. In an attempt to overcome these problems, current research is investigating subunit vaccines. Therefore, we are focusing on the conception of a nanoparticle-based subunit vaccine administered intra-nasally.

Feasibility studies with our vaccine have shown it elicits potent, long-lasting humoral and cell-mediated immunity, as well as providing protection. So the aim of this project is to develop an innovative and efficient synthetic vaccine for veterinary use. We expect that this vaccine would reduce or prevent formation of T.gondii tissue cysts, a source of meat contamination for humans. This vaccine should lower the intra-cerebral and intra-muscular cysts and protect pregnant ewe against abortion if they are contaminated during pregnancy. The standardization of the vaccine formulation in term of antigen preparation, binding to nanoparticles, size, stability and immunogenicity will be assessed to select the optimal formulation for animal clinical studies at the end of this 2-year evaluation.

Project coordinator

Monsieur BETBEDER Didier (Université Lille 2 Droit et Santé - Equipe d'Accueil : Impact de l'environnement chimique sur la santé humaine) – didier.betbeder@neuf.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

SATT NdFV SATT Nord de France Valo SAS
UL2 Université Lille 2 Droit et Santé - Equipe d'Accueil : Impact de l'environnement chimique sur la santé humaine
IPV (Université Tours) UMR Université-INRA ISP 1282 "Immunologie Parasitaire, Vaccinologie et Biothérapie Anti-Infectieuse" UFR de Pharmacie

Help of the ANR 259,205 euros
Beginning and duration of the scientific project: October 2012 - 24 Months

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