Development of a multivalent recombinant vaccine against Toxoplasma gondii in cats

Toxoplasma gondii causes severe human diseases ranging from encephalitis to congenital neurological defects, and is a major cause of zoonotic diseases worldwide. Around a third of the Swiss and the world’s population is chronically infected with this parasite. Although in many individuals toxoplasmosis causes mild or no symptoms, for immunocompromised patients and unborn children the infection is potentially lethal. A few therapies are available to control acute toxoplasmosis, however it is currently impossible to medically eradicate the parasite and cure chronic infections. During a chronic infection Toxoplasma gondii persists in the body in form of a dormant tissue cyst, but is capable of reactivation, thus causing a recurrence of the acute disease.

Toxoplasma gondii infects virtually all warm blooded animals and causes considerable economical losses to the livestock sector. For example, Toxoplasmosis is an important cause of abortion in sheeps, and the economic damage estimated in 1996 in the UK was £18 million. All in all, an effective vaccine against Toxoplasma gondii would be of great benefit for the society.

 

Infection with Toxoplasma gondii occurs either by ingesting oocysts that contaminate soil, water, fruit and vegetables, or by eating cysts in undercooked meat of livestock. Importantly felids are the only definitive host of this parasite, and every human infection results directly or indirectly from cats shedding fertile oocysts into the environment. Blocking oocysts shedding in the environment is therefore crucial to prevent infections.

 

The estimated number of cats in Switzerland is 1.5 million, of which around 50% are freely roaming and therefore continuously exposed to intermediate hosts of T. gondii (i.e., rodents and birds). At any moment, around 1% of cats are shedding up to 55 million T. gondii oocysts per day, and the oocysts survive in the environment for several months. Notably most cats are domestic and regularly visited by a veterinarian, indicating the feasibility of a systematic vaccination program of young cats.

 

The goal of our project is to develop a vaccine to prevent oocyst formation and shedding in cats. We aim at targeting several stages of the Toxoplasma gondii life cycle with a multivalent vaccine based on recombinant proteins. A transcriptomic profiling of various Toxoplasma gondii life cycle stages conducted at our institute in collaboration with the “Molecularbiology Group” highlighted important players that are upregulated during infection in cats (Hehl at al., 2015, BMC Genomics). We are currently establishing the production of selected vaccine candidates in both bacterial and yeast protein expression systems and in the near future we will evaluate the immunogenic potential of the recombinant proteins.

 

Institute members: Prof. Peter Deplazes (Project Co-leader), Prof. Adrian Hehl (Project Co-leader), Dr. Stefania Geiger, Sasa Stefanic, Simone Meier (med. vet.).

Funding sources: KTI Project: 18485.1 PFLS-LS – " The Path to a Transmission-Blocking Vaccine for cats against Toxoplasma gondii: A feasibility Study Using Stage-specific Recombinant Proteins" and National Health and Medical Research Council (Australia; APP1128911, main applicant, N. Smith).

In collaboration with: Prof. Nick Smith (Project Co-leader), Dr. Cibelly Goulart and Dr. Erik Tjhin, Research School of Biology, Australian National University, Canberra, Australia.