Although IL-12 has been widely accepted to play a central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body.

To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly (_DL-lactic-co-glycolic acid) (PLGA).

We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific CD4⁺ and CD8⁺ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of CD8⁺ T cell response was not detectable when CD4⁺ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the CD8⁺ T cell response by IL-12EM is dependent on CD4⁺ T cell "help".

Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.