Will there ever be a universal Staphylococcus aureus vaccine?

Abstract

Developing a universal vaccine for S. aureus is a top priority but to date we have only had failures in human clinical trials. Given the plethora of bacterial virulence factors, broad range of the health of humans at-risk for infections, lack of any information regarding immune effectors mediating protection for any manifestation of S. aureus infection and overall competence of this organism as a colonizer, commensal and pathogen, we may just simply have to accept the fact that we will not get a universal vaccine. Antigenic variation is a major challenge for some vaccine targets and for many conserved targets the organism can easily decrease or even eliminate expression to avoid immune effectors without compromise to infectivity and ability to cause disease. Studies of human immune responses similarly have been unable to identify any clear mediators of immunity and data from such studies can only eliminate those found not to be associated with protection or that might serve as a marker for individuals with a higher level of resistance to infection. Animal studies are not predictive of success in humans and unlikely will be except in hindsight if and when we develop an efficacious vaccine. Successful vaccines for other bacteria based on capsular polysaccharides have not worked to date for S. aureus, and laboratory studies combining antibody to the major capsular serotypes and the other S. aureus surface polysaccharide, poly-N-acetyl glucosamine, unexpectedly showed interference not augmentation of immunity. Potential pathways toward vaccine development do exist but for the foreseeable future will be based on empiric approaches derived from laboratory-based in vitro and animal tests and not on inducing a known immune effector that predicts human resistance to infection.

Keywords: :

• vaccines
• S. aureus
• immunotherapy
• clinical trials
• antibody
• T-cells

Conflict of Interest

GBP is an inventor of Intellectual Properties (IP) (Human monoclonal antibody to PNAG and PNAG vaccine) that are licensed by Brigham and Women’s Hospital (BWH) to Alopexx Vaccines LLC, and Alopexx Pharmaceuticals LLC. As an inventor of the IP, he has the right to receive a share of licensing-related income (royalties, fees) through BWH from Alopexx Pharmaceuticals and Alopexx Vaccines. GBP also holds equity in these two companies. GBP’s interests were reviewed and are managed by the BWH and Partners Healthcare in accordance with their conflict of interest policies.

Acknowledgments

I thank Dr. Colette Cywes-Bentley for provision of the confocal micrographs. Research results related to PNAG vaccines discussed in this review were supported by grants from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) grant numbers AI46706 and AI057159, a component of Award Number U54 AI057159, by a sponsored research agreement with Sanofi, Inc. and by an unrestricted gift from Alopexx Pharmaceuticals LLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.