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 T(H)1-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 mu g ovalbumin (OVA) protein and 16 mu g CpG-ODN adjuvant (MP/OVA/CpG) in comparison to OVA-containing microparticles, soluble OVA plus CpG, or OVA formulated with Alhydrogel (R) aluminum adjuvant Mice vaccinated with MP/OVA/CpG developed the highest T(H)1-associated IgG2b and IgG2c antibody titers, while also eliciting T(H)2-associated IgG1 antibody titers on par with Alhydrogel (R)-formulated OVA, with all IgG subtype titers peaking at day 56. The MP/OVA/CpG vaccine also induced the highest antigen-specific splenocyte IFN-gamma responses, with high levels of IFN-gamma responses persisting until day 42. Thus the MP/OVA/CpG formulation produced a sustained and heightened humoral and cellular immune response, with an overall T(H)1 bias, while maintaining high levels of IgG1 antibody equivalent to that seen with Alhydrogel (R) adjuvant. The time course kinetics study provides a useful baseline for designing vaccination regimens for microparticle-based protein vaccines. (C) 2014 Elsevier Ltd. All rights reserved.