Will there ever be a universal Staphylococcus aureus vaccine?

Developing a universal vaccine for S. aureus is a top priority but to date we have only had failures in human clinical trials. Given the plethora of bacterial virulence factors, broad range of the health of humans at-risk for infections, lack of any information regarding immune effectors mediating protection for any manifestation of S. aureus infection and overall competence of this organism as a colonizer, commensal and pathogen, we may just simply have to accept the fact that we will not get a universal vaccine. Antigenic variation is a major challenge for some vaccine targets and for many conserved targets the organism can easily decrease or even eliminate expression to avoid immune effectors without compromise to infectivity and ability to cause disease. Studies of human immune responses similarly have been unable to identify any clear mediators of immunity and data from such studies can only eliminate those found not to be associated with protection or that might serve as a marker for individuals with a higher level of resistance to infection. Animal studies are not predictive of success in humans and unlikely will be except in hindsight if and when we develop an efficacious vaccine. Successful vaccines for other bacteria based on capsular polysaccharides have not worked to date for S. aureus, and laboratory studies combining antibody to the major capsular serotypes and the other S. aureus surface polysaccharide, poly-N-acetyl glucosamine, unexpectedly showed interference not augmentation of immunity. Potential pathways toward vaccine development do exist but for the foreseeable future will be based on empiric approaches derived from laboratory-based in vitro and animal tests and not on inducing a known immune effector that predicts human resistance to infection.