DEVELOPMENT OF AN ORAL VACCINE AGAINST TUBERCULOSIS BASED ON VIRUS-LIKE PARTICLES

MARTINA MARIANA; GARCIA VERONICA; SPARWASSER TIM; SERRADELL MARIANELA C; BEROD LUCIANA; RUPIL LUCÍA LARA; COLOMBO MARISA; LUJAN HUGO

cordoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

An effective vaccine is urgently needed to fight tuberculosis (TB), the leading cause of death from a single infectious agent worldwide. CBG is the only currently available TB vaccine but it is virtually not effective against adult pulmonary TB. Clinical trials suggest that other systemic vaccines have little advantage over CBG and that mucosal vaccines seem to provide better protection. The goal of our work is to produce an oral vaccine for TB by means of the generation of virus-like particles (VLPs) pseudotyped with Variant-specific Surface Proteins (VSPs) from Giardia lamblia and containing Mycobacterium tuberculosis (Mtb) specific antigens. VLPs are highly immunogenic and also safe and non-infectious. VSPs not only are resistant to proteases and low pH but also show adjuvant activity. We were able to express in HEK cells, expressing or not in their surface the extracellular domain of Giardia VSP1267, the Mo-MLV capsid protein GAG fused to ESAT-6, CFP-10 and Ag85B Mtb antigens. These proteins self-assembled into VLPs with or without VSPs on their surface, and were efficiently purified from the cell supernatant. Initial analysis of oral immunization of mice showed that the VLPs are capable of generating humoral and cellular immune responses against Mtb recombinant antigens. Further studies will provide new insights regarding the efficacy of this formulation to avoid Mtb infections.