Investigating prime-pull vaccination through a combination of parenteral vaccination and intranasal boosting

Roces, Carla B. and Hussain, Maryam T. and Schmidt, Signe T. and Christensen, Dennis and Perrie, Yvonne (2020) Investigating prime-pull vaccination through a combination of parenteral vaccination and intranasal boosting. Vaccines, 8 (1). 10. ISSN 2076-393X

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    Abstract

    Formulation of inhalable delivery systems containing tuberculosis (TB) antigens to target the site of infection (lungs) have been considered for the development of subunit vaccines. Inert delivery systems such as poly(lactic-co-glycolic acid) (PLGA) are an interesting approach due to its approval for human use. However, PLGA suffers hydrolytic degradation when stored in a liquid environment for prolonged time. Therefore, in this study, nano- and microparticles composed of different PLGA copolymers (50:50, 75:25 and 85:15), sucrose (10% w/v) and L-leucine (1% w/v) encapsulating H56 TB vaccine candidate were produced as dried powders. In vitro studies in three macrophage cell lines (MH-S, RAW264.7 and THP-1) showed the ability of these cells to take up the formulated H56:PLGA particles and process the antigen. An in vivo prime-pull immunisation approach consisting of priming with H56:CAF01 (2 x s.c) followed by a mucosal boost with H56:PLGA (i.n) demonstrated the retention of the immunogenicity of the antigen encapsulated within the lyophilised PLGA delivery system, although no enhancing effect could be observed compared to the administration of antigen alone as a boost. The work here could provide the foundations for the scale independent manufacture of polymer delivery systems encapsulating antigens for inhalation/aerolisation to the lungs.