Comparative Efficacy of miniKexin DNA versus protein vaccination against Pneumocystis infection.

Pneumocystis Pneumonia (PCP) is a leading cause of death in individuals with AIDS or other immunocompromised conditions. We have previously shown that mice vaccinated with DNA encoding full-length PC antigen Kex1 have approximately a three-log reduction in PC organism burden after challenge. Full length Kex1 is poorly expressed so to improve on this we developed codon optimized vectors expressing a truncated conserved form of Kex1, mini-kexin. This also allowed investigation of a prime boost strategy since mini-kexin could be efficiently packaged into recombinant adenovirus. Mice were vaccinated with DNA encoding mini-kexin followed by boosting with adenovirus, CD4+ T cells were then depleted by GK1.5, and finally the mice were challenged with live Pneumocystis. The results showed significantly reduced PC burden in vaccinated mice. We then proceeded to generate a protein-based, E coli produced vaccine, however, this time vaccine elicited similar anti-Kex1 titers but lacked protection. We hypothesize that post-translational modification such as glycosylation could play a role in the efficacy of mini-kexin vaccination.