Intranasal immunization in mice with recombinant lactococci expressing the interleukin-12 and the HPV-16 E7 antigen

Interleukin-12 (IL-12), a heterodimeric cytokine, plays an important role in cellular immunity against several bacterial, viral and parasitic infections, and has adjuvant activity when co-delivered with DNA vaccines. IL-12 has also been used with success in cancer immunotherapy treatments. However, systemic IL-12 therapy has been limited by high-level toxicity. Here, we describe the inducible expression and secretion of IL-12 performed in the foodgrade model lactic acid bacterium (LAB), Lactococcus lactis. IL-12 was expressed as 2 separate polypeptides (p35-p40), or as a single recombinant polypeptide (scIL-12). Local administration of IL-12 producing strains at the intranasal mucosal surface resulted in an antigen-specific cellular response (i.e., secretion of Th1 cytokines, IL-2 and IFN- gamma ) elicited by a recombinant L. lactis strain displaying a cell wall-anchored HPV-16 E7 antigen was dramatically increased by co-administration with an L. lactis strain secreting IL-12 protein. This work shows that IL-12 is produced and secreted in active form by L. lactis and that this strategy can be used successfully to enhance an antigen-specific immune response and to stimulate local mucosal immunity.