PSAA encapsulated mucoadhesive polycaprolactone microparticles as potential intranasal vaccine delivery system against pneumococcal infections / by Yamini Gorantla
Pneumococcal infections account for up to 1.6 million deaths annually, and the most affected population are infants and elderly. Streptococcus pneumonia occurs in more than 100 serotypes, but currently used vaccines (Pneumovax and Prevnar) protects only against few serotypes. Hence, there is an immediate need for vaccine that could protect against all serotypes. PsaA (pneumococcal surface adhesin A) is a 37 KDa adhesin, present in all serotypes with minimal structural variation. Our objective was to administer PsaA encapsulated microparticles intra-nasally to induce mucosal and systemic responses, however, the nasal delivery is limited by the mucociliary clearance. Polycaprolactone microparticles were thus coated with mucoadhesive polymers such as chitosan (C), alginate (A) and gelatin (G) to improve mucoadhesion, and further evaluated as vaccine carriers. PsaA encapsulated polycaprolactone microparticles were prepared using double emulsion method. Formulations C, G, A, and various dual coated formulations were tested for their mucoadhesion and immunogenicity in vitro. Nasal targeting potential of these microparticles in mice was evaluated using NIR dye tagged particles. Balb/c mice were vaccinated with PsaA solution, C, G microparticles intranasally (I.N) and uncoated microparticles intra peritoneally (I.P). Lymphocytes from lymphoid tissues were isolated and re-stimulated with antigen to study proliferation, cytokine profile and memory responses. ELISA and Luminex were used to analyze antibody and cytokine titers respectively. Formulations C, G, alginate & gelatin at different ratios (AG) showed optimum immunogenicity and mucoadhesion, amongst which C and G significantly improved (p ≤ 0.05) nasal retention in vivo. Mice vaccinated with uncoated (I.P) and G (I.N) induced high (p ≤ 0.05) anti-PsaA IgG responses (IgG2a ~ IgG1 >>> IgG3), while only G induced high mucosal anti-PsaA IgA (p ≤ 0.05). Both proliferation and cytokine responses indicates comparable cellular responses in spleen for all the treatments, while only G and C induced high responses in mucosal tissues. High induction of IL-6 and IL-10 was observed in the mice that received G and C (I.N). PsaA encapsulated Gelatin coated microparticles delivered I.N induced high anti-pneumococcal responses in both mucosal and systemic sites. The systemic response induced was comparable to parenterally delivered microparticles.