Time course study of the antigen-specific immune response to a PLGA microparticle vaccine formulation

Microparticle-based vaccine delivery systems are known to promote enhanced immune responses to protein antigens and can elicit TH1-biased responses when used in combination with Toll-like receptor (TLR) agonists. It is important to understand the kinetics of the immune responses to microparticle-based protein vaccines in order to predict the duration of protective immunity and to optimize prime-boost vaccination regimens. We carried out a 10-week time course study to investigate the magnitude and kinetics of the antibody and cellular immune responses to poly(lactic-co-glycolic acid) (PLGA) microparticles containing 40 μg ovalbumin (OVA) protein and 16 μg CpG-ODN adjuvant (MP/OVA/CpG) in comparison to OVA-containing microparticles, soluble OVA plus CpG, or OVA formulated with Alhydrogel(®) aluminum adjuvant. Mice vaccinated with MP/OVA/CpG developed the highest TH1-associated IgG2b and IgG2c antibody titers, while also eliciting TH2-associated IgG1 antibody titers on par with Alhydrogel(®)-formulated OVA, with all IgG subtype titers peaking at day 56. The MP/OVA/CpG vaccine also induced the highest antigen-specific splenocyte IFN-γ responses, with high levels of IFN-γ responses persisting until day 42. Thus the MP/OVA/CpG formulation produced a sustained and heightened humoral and cellular immune response, with an overall TH1 bias, while maintaining high levels of IgG1 antibody equivalent to that seen with Alhydrogel(®) adjuvant. The time course kinetics study provides a useful baseline for designing vaccination regimens for microparticle-based protein vaccines.