Systematic mapping review of preclinical and clinical studies of Staphylococcus aureus vaccines

Staphylococcus aureus is a pathogen that annually causes more than one million deaths globally. However, despite substantial research, no vaccine for human use has yet been licensed. We conducted a systematic mapping review to evaluate the different pre-clinical and clinical approaches taken in Staphylococcus aureus (S. aureus) vaccine development as well as veterinary vaccines. We examined the testing frequency of different antigens, platforms, routes of immunisation, types of immune response and pre-clinical challenge models. We identified and analysed 358 relevant publications in PubMed. More than 150 antigens were studied in preclinical trials, with alpha-hemolysin (Hla) being the most frequently tested antigen. With respect to pre-clinical challenge models, systemic infections have been studied for the longest period and are the most widely used. Subunit vaccines were the most studied platform; this includes toxoids and polysaccharide antigens. Complete Freund's Adjuvant was the most common adjuvant used and, surprisingly, is still frequently used in recent studies. Antibody titre was the most frequently assessed vaccine-induced immune parameter and opsonophagocytosis has been the most common functional humoral readout. This review identifies trends for the development of a S. aureus vaccine, and highlights the lessons learned from past failures and the opportunities for current and future development. This quantitative evidence identifies predominant themes in the S. aureus vaccine field and therefore contributes to highlighting less explored gaps and potential new avenues of research in ongoing efforts to developing urgently needed, effective S. aureus vaccines.