DEVELOMPENT OF AN ORAL RESPIRATORY SYNCYTIAL VIRUS VACCINE BASED ON VIRUS LIKE PARTICLES BEARING GIARDIA LAMBLIA?S SURFACE PROTEINS

BUENO CARLOS; RUPIL LUCÍA LARA; SERRADELL, MARIANELA DEL CARMEN; GARGANTINI PABLO RUBÉN; LUJAN HUGO D

Conferencia; 6th Resvinet conference; 2021

Mucosal vaccines elicit immune responses, secretory IgA and mucosally imprinted lymphocytes that provide protection at the first line of defence of the organism where the majority of pathogens enter. But, to achieve proper bioavailability mucosal vaccines must avoid antigen degradation by proteases. We have recently developed a vaccine platform that leverages the properties of Giardia lamblia?s variant-specific surface proteins (VSPs) to allow oral immunization of subunit vaccines. VSPs cover the entire surface of this parasite that inhabits the upper gastrointestinal tract where digestive enzymes have their highest concentration. Since VSPs are resistant to proteolysis, we engineered them to accommodate at a virus like particle (VLP), and demonstrated that they could confer protection to a viral antigen displayed on the particle. As a proof of concept, mice were orally immunized with VLPs containing glycoproteins of influenza virus and VSP1267. Immunized mice generated an efficient humoral and cellular, mucosal and systemic immune response that protected them from infection with the virus and from tumours expressing viral antigens. These exciting results prompted us to study the application of this platform as a potential respiratory syncytial virus vaccine. The fusion and attachment glycoprotein sequences have been cloned in expression vectors and the production and validation of VLPs are currently being evaluated. Next, we plan to administer these particles to mice and analyse the immune response and the protection from infection. The results obtained will shed light on the mechanisms of VLP-VSP vaccines and provide information on the attractive oral vaccination strategy for RSV prevention.