Failure of a vaccine using immunogenic recombinant proteins rNcSAG4 and rNcGRA7 against neosporosis in mice

Characterisation of NcGRA7 and NcSAG4 proteins: Immunolocalisation and their role in the host cell invasion by Neospora caninum tachyzoites

“…Similar to other specific-bradyzoite proteins in T. gondii (Di Cristina et al 2004), its immunogenicity seems to be reduced when compared to secreted/excreted proteins (Aguado- Martínez et al 2008Martínez et al , 2009a). This reduction serves as an immune evasion mechanism, allowing it to persist in the host (Kim and Boothroyd 2005).…”

A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis

“…In addition, we assume that this response remained active after the infection, since sera from vaccinated and challenged animals recognized the same specific bands by Western blotting. Hence, the lack of a protective effect cannot be attributed to a lack of immune stimulation against the original protein as reported in previous studies (Cannas et al, 2003a;Aguado-Martínez et al, 2009;Jiménez-Ruiz et al, 2012).…”

“…In the present work, NcROP40 and NcNTPase, which are more abundantly expressed in high virulence isolates (Regidor-Cerrillo et al, 2012), were expressed as recombinant proteins and assessed as vaccine candidates, either as monovalent vaccines or in combination with NcROP2 and NcGRA7 (Aguado-Martínez et al, 2009;Debache et al, 2009;Jiménez-Ruiz et al, 2012). Combining these vaccine candidates into a polyvalent formulation was done in anticipation to increase the efficacy of final formulations, since these antigens were selected based on their predicted functional role during the tachyzoite lytic cycle (Coppens et al, 1999;Ferguson, 2004;El Hajj et al, 2006;Cesbron-Delauw et al, 2008).…”

“…Particularly, proteins located in micronemes, rhoptries and dense granules, organelles whose contents are involved in tachyzoite host cell adhesion and invasion, have emerged as promising vaccine targets to block parasite dissemination and foetal transmission during the acute phase of infection . Vaccine candidates have been traditionally selected based on their immunogenic capacities (Ellis et al, 2008), their role in tachyzoite to bradyzoite stage conversion (Aguado-Martínez et al, 2009;Jiménez-Ruiz et al, 2012;Uchida et al, 2013) and their implication in adhesion or invasion processes (Debache et al, 2009;Monney et al, 2011), with variable results in experimental mouse models. Recently, proteome expression changes in different isolates revealed that the rhoptry protein NcROP40 and the dense granule protein NcNTPase are more abundantly expressed in virulent isolates compared to isolates of low virulence (Regidor-Cerrillo et al, 2012).…”

“…Furthermore, vaccination of mice with recombinant NcROP2 was shown to protect mice against neosporosis (Debache et al, 2008(Debache et al, , 2009(Debache et al, , 2010Monney et al, 2011). On the other hand, NcNTPase was shown to form a complex with the immunodominant dense granule antigen NcGRA7, whose efficacy as a recombinant vaccine was also assessed in mice (Aguado-Martínez et al, 2009;Jiménez-Ruiz et al, 2012). In T. gondii tachyzoites, the expression of the two dense granule antigens TgGRA7 and TgNTPase is essential for active replication (Coppens et al, 1999;Cesbron-Delauw et al, 2008).…”