Format

Send to

Choose Destination
FEMS Microbiol Rev. 2019 Dec 16. pii: fuz030. doi: 10.1093/femsre/fuz030. [Epub ahead of print]

Development of a vaccine against Staphylococcus aureus invasive infections: Evidence-based on human immunity, genetics, and bacterial evasion mechanisms.

Miller LS1,2,3,4, Fowler VG5,6, Shukla SK7,8, Rose WE9,10, Proctor RA9,11.

Author information

1
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
5
Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
6
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, United States of America.
7
Center for Precision Medicine, Marshfield Clinic Research Institute, Marshfield, WI, USA.
8
Computation and Informatics in Biology and Medicine, University of Wisconsin, Madison.
9
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
10
Pharmacy Practice Division, University of Wisconsin-Madison, Madison, WI, USA.
11
Department of Medical Microbiology/Immunology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Abstract

Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread emergence of virulent and multi-drug resistant methicillin-resistant S. aureus strains. There is an urgent and unmet clinical need for non-antibiotic immune-based approaches to treat these infections as the increasing antibiotic resistance is creating a serious threat to public health. However, all vaccination attempts aimed at preventing S. aureus invasive infections have failed in human trials, especially all vaccines aimed at generating high titers of opsonic antibodies against S. aureus surface antigens to facilitate antibody-mediated bacterial clearance. In this review, we summarize the data from humans regarding the immune responses that protect against invasive S. aureus infections as well as host genetic factors and bacterial evasion mechanisms, which are important to consider for the future development of effective and successful vaccines and immunotherapies against invasive S. aureus infections in humans. The evidence presented form the basis for a hypothesis that staphylococcal toxins (including superantigens and pore-forming toxins) are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis.

KEYWORDS:

Evasion; Genetics; Immunity; MRSA; Staphylococcus aureus; Vaccine

PMID:
31841134
DOI:
10.1093/femsre/fuz030

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center