Solving the Staphylococcus aureus puzzle: lessons to guide future MRSA vaccine development

SUMMARYThe broad-spectrum use of antibiotics allows for the development of resistance in symptomatically and asymptomatically carried pathogenic bacteria. Antibiotic-resistant bacteria, with this review focusing on Staphylococcus aureus, cause significant morbidity and mortality and put considerable strain on the global healthcare system. In a vaccinated individual, bacteria are less likely to develop resistance mechanisms compared to an individual treated with antibiotics, highlighting a potential method for conserving antibiotic use. However, despite over a century of research, a S. aureus vaccine candidate is yet to progress past phase III clinical trials, and to develop a successful S. aureus vaccine, the shortcomings of previous attempts require critical analysis. After consideration of the five most successful S. aureus vaccine programs, it is identified in this review that future attempts should (i) be polyvalent to circumvent immune evasion, (ii) include carefully chosen antigens to avoid maladaptive memory, (iii) include T cell targeting to provide a comprehensive immune response, (iv) utilize multiple measures of preclinical efficacy in pre-exposed models, and (v) implement considered clinical study design, including appropriate vaccine formulation for the target population. By combining these attributes, such as in the form of epitope-based or nanoparticle vaccines, there is a promising future for the development of S. aureus vaccines that circumvent the issues that caused the downfall of previous vaccine programs, thereby protecting the global population from development toward a future where bacteria are resistant to all antibiotic treatments.