Biodegradable poly-l-lactide based microparticles as controlled release delivery system for filarial vaccine candidate antigens

Abstract

Modern recombinant vaccines are less immunogenic than conventional vaccines which require adjuvants to enhance the effect of a vaccine. Alum is being used as a standard adjuvant for protein based vaccines to augment immune response in several diseases. However, the problem associated with alum is it requires multiple doses at specific time intervals to achieve the adequate level of immunity. Currently the adjuvanticity of Poly-l-lactide microparticles as single dose immunization was explored to overcome multiple immunization and reported to be effective for several diseases. In this regard we adsorbed filarial recombinant chimeric multivalent vaccine candidates such as TV and FEP on to PLA by double emulsion method and analyzed the characterization of PLA encapsulated microparticles and evaluated its immune responses in mice. The efficacy of single dose of PLA encapsulated proteins was investigated in comparison with single dose of alum or protein alone. In mice, single dose of PLA encapsulated antigens such as TV and FEP elicited significantly high antibody titer of 50,000 and 64,000 respectively than single dose of alum adsorbed TV/FEP (6000/9000) and single dose of protein TV/FEP (3000/4000) alone. Further PLA encapsulated antigens induced higher levels of cellular proliferation together with significant (P<0.0001) levels of cytokine response [PLA-TV induced high levels of IL-4(Th2) and IFN-γ (Th1) cytokines whereas PLA-FEP showed high levels of IL-5(Th2) and IFN-γ (Th1)] indicating a balanced response elicited by PLA antigens. Overall strong humoral and cellular responses were observed for PLA encapsulated antigens compared with single dose of alum adsorbed or protein alone.

Keywords: Acetonitrile; Adjuvants; Controlled release delivery system; Dichloromethane; Immune response; Lymphatic filariasis; Microsphere; Poly-l-lactide; Poly-l-lactide (PLA); Polyvinyl alcohol (PVA).