Vaccine model based on recombinant hydrophobic protein and saponin

The Bd37 is an erythrocyte binding protein anchored at the surface of the parasite Babesia divergens. B. divergens is an Apicomplexa parasite, mostly of veterinary importance but able to infect humans after tick-bites. The lab model of bovine and human babesiosis is provided by the gerbils Meriones unguiculatus infected by Babesia divergens.rnRecombinant hydrophobic Bd37 is able to induce complete protective immune response when mixed with saponin, in contrast to hydrophilic Bd37 which only induce non-protective antibodies.

Interest / Relevance: Vaccine based on recombinant proteins, as well as efficient adjuvants, are challenging to develop. Interestingly, combination of hydrophobic recombinant protein and saponin has been successfully used in CoVID-19 vaccine from NOVAVAX and in the R21 vaccine against malaria.rnThe Bd37 vaccine model allows shifting from an inefficient to a fully protective immune response using hydrophobic peptide sequence and saponin. So this model is ideal to study protective and unprotective immune responses from basic point of view, to try correlate of protection discovery pipeline etc...rnRanging from in vitro to in vivo experiments, this vaccine model can also be used in the development of new vaccine formulation and efficient adjuvant.rn

Keywords: POC in vivo, vaccine, Apicomplexa, parasite, adjuvant,

Scientist's name: Stéphane DELBECQ
Schetters TPM

Publications:

1: Delbecq S. Major Surface Antigens in Zoonotic Babesia. Pathogens. 2022 Jan 1511(1):99. doi: 10.3390/pathogens11010099.rnrn2: Nathaly Wieser S Schnittger L Florin-Christensen M Delbecq S Schetters T.rnVaccination against babesiosis using recombinant GPI-anchored proteins. Int JrnParasitol. 2019 Feb49(2):175-181. doi: 10.1016/j.ijpara.2018.12.002. rnrn3: Delbecq S Auguin D Yang YS Löhr F Arold S Schetters T Précigout ErnGorenflot A Roumestand C. The solution structure of the adhesion protein Bd37rnfrom Babesia divergens reveals structural homology with eukaryotic proteinsrninvolved in membrane trafficking. J Mol Biol. 2008 Jan 11375(2):409-24. doi:rn10.1016/j.jmb.2007.08.019. rnrn4: Hadj-Kaddour K Carcy B Vallet A Randazzo S Delbecq S Kleuskens JrnSchetters T Gorenflot A Precigout E. Recombinant protein Bd37 protectedrngerbils against heterologous challenges with isolates of Babesia divergensrnpolymorphic for the bd37 gene. Parasitology. 2007 Feb134(Pt 2):187-96. doi:rn10.1017/S0031182006001399. rnrn5: Delbecq S Hadj-Kaddour K Randazzo S Kleuskens J Schetters T Gorenflot ArnPrécigout E. Hydrophobic moeties in recombinant proteins are crucial to generaternefficient saponin-based vaccine against Apicomplexan Babesia divergens. Vaccine.rn2006 Jan 3024(5):613-21. doi: 10.1016/j.vaccine.2005.08.073.

Detailed technology overview: This vaccine model use gerbils (Meriones unguiculatus) as host, which are immunized with positive and negative Bd37 vaccines. Immunization schedule consists in two injections at 3 weeks intervals, then infectious challenge is performed. Living parasites from in vitro culture are injected by IP route in gerbils. The infection develops in 3-10 days and clinical signs are monitored daily (parasitemia and haematocrit) by blood sampling at the tail. The positive Bd37 vaccine induce a complete protection, both against parasites (no infection) and diseases (no clinical signs). So any modification of the antigen Bd37 (either new hydrophobic sequence, lipids, etc…) could be tested, as well as new adjuvants or even new vaccine technologies (mRNA, nanoparticles…).

Reference:

RT00511