Inferring Reasons for the Failure of Staphylococcus aureus Vaccines in Clinical Trials

Multidrug resistant Staphylococcus aureus strains are emerging and current antibiotics are not efficacious against such strains. Therefore, there is an urgent need to develop vaccines to target this pathogen. However, both active and passive immunization strategies have thus far failed to show efficacy in humans. There are several potential reasons behind the disappointing results of clinical trials, however, we believe that just a few of them, which are common to all the trials, determined their downfall. First of all, preclinical results obtained with antigens tested in clinical trials were likely overestimated by vaccine manufacturers. Furthermore, vaccines tested in humans to date, since they all targeted single antigens, were probably disproportionate to the complex pathogenic mechanisms of the bacterium. In addition, the lack of known correlates of protection in humans has severely limited the ability to interpret both preclinical and clinical data. Finally, the vaccines did not contain new generation adjuvants, which may be critical in augmenting antibody production and steering the T-cell response toward the proper profile of cytokine production.