Considering the ‘Alternatives’ for Next-Generation Anti-Staphylococcus aureus Vaccine Development

Staphylococcus aureus is an opportunistic pathogen, which can readily develop antibiotic resistance and result in severe disease. To combat antibiotic resistance, new treatment strategies are being developed with a particular focus on vaccine development. S. aureus vaccines that target humoral immunity alone do not provide sufficient protection from all disease phenotypes associated with this pathogen. Recent studies have identified the requirement for cellular immunity to provide a robust immune response to this infection. Driving conventional T cell responses has therefore become the focus of intense research in this area. Recently described ‘alternative’ T cells could provide a novel strategy for improving therapeutic efficacy and success in next-generation anti-S. aureus vaccine design. Antibody responses alone are not sufficient to drive protective immunity to S. aureus infection; cellular immunity is also required. γδ T cells are particularly important in the production of IL-17 at the early stages of S. aureus infections in mice. Similar human IL-17-producing γδ cells have yet to be described in S. aureus-infected individuals. Other alternative lymphocyte subsets such as ILCs and MAIT cells, which can produce IFN-γ and IL-17, directly target infected cells and bacteria, and potentially have other immunomodulatory functions. These have also been implicated in the immune response to S. aureus. Alternative lymphocyte subsets can develop a memory phenotype, are localised to specific tissues, and respond rapidly to stimuli, making them a first-line of defence, which could be targeted in vaccine formulations. How alternative cells are involved in S. aureus infection and what potentially novel ligands they respond to has yet to be fully established and requires further study.