Recombinant TcP21 as potential adjuvant for Trypanosoma cruzi vaccines based on live attenuated parasites

PEREZ BRANDAN C; MESIAS AC; TEIXEIRA, TL; VIEIRA DA SILVA C

Santa Fe

Simposio; XXVIII Reunión Anual de la Sociedad Argentina de Protozoología y Enfermedades Parasitarias - SIMPOSIO Internacional de Biología Celular y Molecular de la Enfermedad de Chagas; 2016

Sociedad Argentina de Protozoología

In the last years, vaccine research against Trypanosoma cruzi has gained renew attention due, mainly, to the advances in vaccine technology and to economic models predicting that a therapeutic or prophylactic vaccine wouldbe useful as an additional tool to control Chagas Disease in endemic areas. Several parasite antigens as well as DNA plasmids administered alone or in recombinant bacteria or virus as a delivery system have been evaluated showingpromising results for further vaccine development. TcP21 is a ubiquitous secreted protein of T. cruzi and its role during parasite cell invasion is not completely understood yet. However, recombinant TcP21 promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerization. Our goal was to study the immunogenicity and protective efficacy of therecombinant protein TcP21 in a mouse model of T. cruzi infection. For this purpose groups of mice were intraperitoneally vaccinated with therecombinant protein emulsified in saponin, given alone or in combination with live attenuated parasites, which have already demonstrated toinduce a strong protective effect. Three weeks later, mice were given a similar booster vaccine. Four weeks after the last immunization, animalswere challenge with a lethal dose of T. cruzi parasites. During the immunization period sera samples were collected for parasite specific IgGs and IgGs subtypes quantification and cytokines detection. Spleen was removed for lymphocytesisolation and further proliferation assays and cytokine production determination. After challenge, parasite load was recorded twice aweek. Our results showed that when administeredalone, recombinant TcP21 does not confer protection against a lethal challenge; however, when TcP21 is formulated with live attenuated parasites the protective capacity seems to beimproved compared to the one obtained by immunization with live attenuated parasite alone. So far these results create the impression thatrecombinant TcP21 per se is not a good inducer of a protective response, nevertheless its incipient adjuvant properties leave the possibility to furtherevaluate this protein in view of generating new multicomponent vaccine formulations. This work is supported by Agencia Nacional de PromociónCientífica y Técnica.