Ying Men

Revisiting PLA/PLGA microspheres: an analysis of their potential in parenteral vaccination.

Poly(lactide) and poly(lactide-co-glycolide) microspheres have been studied for controlled antigen delivery and immune response enhancement for more than a decade. Early developments of such vaccines were basically technology-driven, stemming from the well-established biocompatibility of these polymers in concert with their innate properties to tailor rates of bioerosion and release. More recently, other features have become equally or even more appealing, such as the adjuvancy of such microspheres and their ability to elicit cellular effector responses, so-called cytotoxic T-cell responses, in addition to antibody responses observed already in the very early studies. In this review, we intended to revisit microsphere-based vaccines designed for the parenteral route and attempted to outline major developmental issues, as well as to analyze immunological fundamentals and data associated with antigen delivery by microspheres.

Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic peptides and human compatible adjuvants.

The goal of this study was the induction of a strong CTL response against multiple CTL epitopes present in HIV proteins using short synthetic peptides. Four HLA-A2.1 restricted peptides (RT 476-484, p17 77-85, gp41 814-823, RT 956-964) that showed stable binding to the HLA-A2.1 molecule in an in vitro binding assay were able to elicit a strong specific immune response in HLA-A2.1 transgenic mice when injected with IFA or Montanide. The use of biodegradable microspheres (MS) as adjuvant was also successfully tested for all peptides. When the peptides were injected as a mixture the response was weaker as compared to individual injections of the peptides indicating the occurrence of immunodominance (ID). We are currently investigating whether ID can be overcome by a combined injection of peptide loaded MS with different release patterns. Taken together, it seems feasible to induce a specific CTL response in HLA-A2.1 transgenic mice against several HIV proteins using short synthetic peptides and human compatible adjuvants.