Immunotherapies and Vaccines against Diseases Caused by Staphylococcal Toxins

Dear Colleagues,

Staphylococcus aureus (SA) is a human commensal and, at the same time, formidable pathogen that can cause a wide range of diseases, from skin and soft tissue infections to life threatening bacteremia, pneumonia, surgical site infections, and osteomyelitis. The growing prevalence of methicillin-resistant SA (MRSA), as well as multidrug resistant strains, represents a major public health challenge. SA has a large arsenal of virulence factors that help establish the infection and to evade host immune defenses.  Several of these factors, notably, all cell-associated, were evaluated as vaccine and immunotherapy targets in human efficacy trials, but they all either lacked efficacy or resulted in more severe disease. S. aureus also produces many secreted toxins that modulate host immune responses, kill key innate immune cells, intoxicate components of the adaptive immune response, cause barrier dysfunction enabling bacterial dissemination, help extract nutrients from the host, cause excessive inflammation, promote platelet aggregation, and induce toxic shock. These toxins include pore-forming toxins (PFTs), including alpha hemolysin and bicomponent PFTs; more than twenty superantigens (SAgs); SAg-like toxins (SSLs); delta toxin; phenol soluble modulins (PSMs); and exfoliative toxins. Recent data in several animal models indicate that neutralizing key toxins can facilitate immune-mediated SA clearance. Epidemiologically, some of these toxins, such as Panton-Valentine leukocidin (PVL) and PSM, have been linked to the emergence of community acquired MRSA (CA-MRSA) in the past two decades. Alpha hemolysin and PVL have emerged as critical virulence factors for necrotizing pneumonia and skin and soft tissue infections. Superantigens are the main cause of staphylococcal toxic shock syndrome (TSST) and food poisoning, and are also implicated in atopic dermatitis and other forms of allergic diseases.

Thus, staphylococcal toxins should be considered important targets of vaccine and immunotherapy. While animal studies and epidemiological evidence support this notion, many questions and challenges remain to be addressed.  Which one of the numerous toxins produced by S. aureus must be targeted, and for which staphylococcal syndromes? Can the neutralization of toxins prevent infection? Can severity endpoints be defined that allow for measurable clinical outcomes? Can anti-toxin strategies be used to mitigate flares of atopic disease?

The focus of this Special Issue of Toxins is on staphylococcal toxins as the target of vaccines and immunotherapy. This will include a wide range of topics, such as a deeper understanding of the interaction of the toxins with the host; immune modulation by the toxins and its role in pathogenesis; epidemiological and clinical evidence for the role of toxins in SA diseases; and animal models and studies evaluating toxoid vaccine or anti-toxin immunotherapeutic candidates.

Dr. M. Javad Aman
Guest Editor

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• Staphylococcus aureus
• staphylococcal toxins
• pore-forming toxins
• superantigens
• immunotherapy
• toxoid vaccine
• immune evasion
• anti-virulence vaccine