Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

Abstract

Staphylococcus aureus is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against S. aureus have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Translational science studies are attempting to discover correlates of protection using animal models as well as in vitro and ex vivo models assessing efficacy of vaccine candidates. Several new vaccine candidates are being tested in human clinical trials in a variety of target populations. In addition to vaccines, bacteriophages, monoclonal antibodies, centyrins and new classes of antibiotics are being developed. Some of these have been tested in humans with encouraging results. The complexity of the diseases and the range of the target populations affected by this pathogen will require a multipronged approach using different interventions, which will be discussed in this review.

Keywords: Staphylococcus aureus; host-pathogen interactions; humoral immunity; models of infection; vaccinology.

Figure 1

Methods of targeting Staphylococcus aureus. There are numerous therapies being investigated as treatments for S. aureus infections. Antibiotics are currently the only option with clinical approval. Antibiotics act directly on bacteria via either bacteriostatic or bactericidal mechanisms. Bacteriophages also act directly on S. aureus to kill bacteria. Centyrins are small proteins with the ability to neutralize bacterial exo-toxins and virulence factors. Monoclonal antibodies can act in the same manner as centyrins to neutralize bacterial exo-toxins and virulence factors, with a secondary mechanism of opsonizing the bacteria due the presence of antibody Fc regions. Vaccines generate populations of memory B and T cells. B cells produce antibodies that act in the same manner as described for monoclonal antibodies. Memory T cells can also be induced which, through pro-inflammatory cytokines such as IFN-γ and IL-17, aid in the activation and recruitment of innate effector cells such as Macrophage (Mφ) and Neutrophils (PMN) which in turn kill bacteria. While CD4⁺ T cells have a more classical role in adaptive memory responses, there is growing evidence to suggest that γδ T cells may be induced by vaccination and play a protective role during S. aureus infections (–13).