Sting agonist and antigen design as a vaccine model to combat parasitic chronic infections

SANCHEZ ALVERTI A; BIVONA A; CERNY N; CAZORLA SI; SCHULZE, K; WEIßMANN, S; EBENSEN, T; GUZMAN C; MALCHIODI EL

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Simposio; KEYSTONE SYMPOSIA on Molecular and Cellular Biology; 2014

KEYSTONE SYMPOSIA on Molecular and Cellular Biology

T. cruzi is an obligatory intracellular parasite recognized by WHO as a neglected tropical disease, which affects 10-12 million people in Latin America. After 100 years of its discovery, there are still no effective vaccines or drugs to prevent or treat the infection. In this work we combined rational design of the Immunogen in order to achieve a multivalent display of key parasitic cytotoxic T lymphocytes (CTL) and antibodies targets as well as to omit known Immune evasion associated sequences. In search of novel components that can increase the levels of CTL response we have employed cyclic di nucleotides (CDNs) ? 3?5?-c-di-AMP (STING agonist) with rProtein or DNA-prime + rProtein-boost ? in vaccination protocols by the intranasal route. With these strategies we have been able to obtain not only an excellent humoral immune response that blocked in-vitro infection (more than 60% vs. preimmune serum p