title: rhIL-12 as adjuvant augments lung cell cytokine responses to pneumococcal whole cell antigen.
abstract: Conjugate pneumococcal vaccines offer suboptimal protection against mucosal infections and are restricted in serotype and geographical coverage. New protein-based vaccines using conserved pneumococcal antigens and better mucosal adjuvant technology are urgently needed. Interleukin-12 (IL-12) has shown efficacy as a pneumococcal protein vaccine adjuvant in murine models of pneumococcal infection. Systemic administration of recombinant human (rh) IL-12 to humans, however, has been associated with adverse clinical and laboratory side effects. Inhaled forms of IL-12 have improved the safety profiles in humans, as suggested by animal models. Here we evaluated rhIL-12 as an adjuvant on ex vivo human BAL cells when stimulated with pneumococcal whole cells. We show that co-incubation of ex vivo human BAL cells with pneumococcal whole cell antigen (WCA) and a low dose of rhIL-12 (2 ng) can elevate TNF production compared to treatment with WCA (p=0.06) or rhIL-12 (p=0.03) alone. The production of IFNγ was also increased but not in an antigen specific manner, suggesting perhaps a predominant Th(1) response. Our data suggest that 100-200-fold lower doses of inhaled rhIL-12 than those previously tested for systemic use may be adequate in a phase 1 study and commend further evaluation of rhIL-12 as a potential mucosal adjuvant in human vaccine studies.
authors: Biomedical Research Centre in Microbial Diseases, National Institute of Health Research, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. adam.wright@liverpool.ac.uk
authors: Adam K A
authors: AK
authors: Wright
authors: Ioanna
authors: I
authors: Christopoulou
authors: Sherouk
authors: S
authors: El Batrawy
authors: Jane
authors: J
authors: Limer
authors: Stephen B
authors: SB
authors: Gordon