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.
Highlights
Staphylococcus aureus is a gram-positive bacterium responsible for significant morbidity and mortality worldwide
We propose that the usage of more relevant animal models, more representative in vitro models and ex vivo human tissues to study the pathogenicity of S. aureus will increase the fidelity of data obtained at the preclinical level and increase the likelihood of vaccines entering into clinical trials being efficacious
We aim to provide this information while using evidence from past failings regarding S. aureus vaccine design, as well as lessons learned from non-S. aureus vaccine research, to provide a critical discussion of current research activities in order to pave the way for future research efforts in the field
Summary
Staphylococcus aureus is a gram-positive bacterium responsible for significant morbidity and mortality worldwide. The efficacy of successful humanization as measured by the ratio of human to murine CD45+ cells was directly correlated with the size of skin abscesses in mice and skin lesions were significantly reduced in humanized mice when a PVL-deficient strain of S. aureus was used, an effect not observed in wild-type mice [102] These findings combine to suggest that S. aureus host-specificity is a crucial factor for the outcome of infection and that humanization of mice may be a highly useful tool to increase the translatability of preclinical vaccine data [105]. Another lesson from SA4Ag’s failure is that while retrospective analysis of Nabi’s StaphVax vaccine seemed to indicate that waning antibody titres might lead to a decreased efficacy overtime [19], here SA4Ag was shown to induce lasting humoral responses for periods of time longer than
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
