The Problem

Increasing emergence of antibiotic-resistant strains of staphylococci in the human and veterinary medicine marketplace will hamper chemotherapeutic treatments of these infections. New antibiotics which will efficiently kill these antibiotic-resistant strains will apparently not be readily available in the near future. 

The Solution

Immunology Laboratories, Inc. (ImmLab) has patented and patent pending, novel technological inventions for the treatment of staphylococcal infections in humans and animals.

ImmLab has been granted Patent 6,929,798 from the United States Patent and Trademark Office for its “Compositions and Methods for Treatment of Microbial Infections”.  ImmLab is continuing to expand its intellectual property portfolio with a proactive strategy to insure maximum protection for technologies which it has obtained or developed.

Microbiological Aspects of S. aureus Infections

Staphylococci are gram-positive bacteria represented by more than a dozen species ranging from those indigenous to normal flora of the skin, and mucosal surfaces, to highly virulent pathogens. Among the many staphylococci species, S. aureus is among the most common and most virulent forms of staphylococci encountered throughout history, from the pre-antibiotic era to the present time.

Staphylococcal infections are characterized by intense suppuration, necrosis of local tissues, and a tendency for the infected area to form "walled off" abscesses. S. aureus can cause skin infections (furuncles, carbuncles, and impetigo) as well as deep lesions from bacteria spread from skin lesions (bones, joints, soft tissues, and deep organs). S. aureus is also a major cause of wound infections.  Surgical wound infections may be very severe and even fatal at times. S. aureus can produce various toxins causing scalded skin syndrome, toxic shock syndrome, and staphylococcal food poisoning.   

Treatments of staphylococcal infections with antibiotics were originally very successful. However, after many years use of beta-lactam antibiotics, S. aureus became resistant to many classes of antibiotics.  MRSA strains manifest increasing prevalence in hospital-acquired infections as well as in nosocomial and community-onset infections. Vancomycin, as the "last resort" antibiotic, is still effective but reports on emergence of VISA indicate that this situation is changing rather rapidly.  Antibiotic resistance in a bacterium is usually conferred by plasmid-encoded genes, and as such, resistance genes can be transferred to antibiotic-susceptible strains from reservoir strains containing these resistance genes.  

According to a July 13, 2005 Wall Street Journal article, a Pennsylvania state agency conducted a study regarding hospital-acquired infections. The article indicated that the “…agency has found that 11,668 hospital-acquired infections were associated with 1,793 deaths, 205,000 extra hospital days and $2 billion in additional hospital charges last year”. The article goes on to say, “Extrapolating from the Pennsylvania data to the rest of the country suggests that more than 125 people a day are dying from hospital-acquired infections with an associated $50 billion of related hospital charges every year…”  

Most community-acquired infections of S. aureus are autoinfections, with strains being carried in the anterior nares or on the skin.  Hospital epidemics, on the other hand, are caused by highly virulent and antibiotic-resistant strains of S. aureus associated with patients undergoing invasive treatments. These epidemics are a continuing and recurrent problem. S. aureus strains produce a variety of substances that may contribute to their virulence. The most important factors include alpha-hemolysin, pyrogenic exfoliatins, coagulase, protein A, and other extracellular enzymatically active substances. 

Although a variety of phenotypes and products appear to contribute to S. aureus virulence, no one factor can be singled out as the primary contributor to its ability to multiply and cause lesions in the tissues. Therefore, a single candidate for an effective immunization appears unlikely. Natural immunity to staphylococcal infections is of short duration and incomplete, although involving both humoral and cellular mechanisms. Obviously, a different approach to vaccination is in order.  

Based on years of research and development in Europe, a novel preventative and therapeutical approach has been developed by ImmLab. This approach is based on use of a broad-range of antigens derived from staphylococcal cells. 

Immunity to Staphylococcal Infections

Resistance of human organism against bacterial pathogens involves both innate and adaptive immunity. Innate immunity provides mechanisms for immediate protection against a wide variety of pathogens. It includes:

•      a pattern recognition system for the pathogens

•     activation of effector mechanisms quickly destroying the pathogens

•     pathways that can activate adaptive immunity   

Adaptive immunity provides responses to persistent pathogens, and has both humoral and cellular components. Innate response to pathogens initiates, controls and instructs the adaptive immune response. In order to establish a persistent infection, bacterial pathogens posses a plethora of mechanisms (so called virulence factors) to overcome the multi-layered host defenses.

S. aureus is a human and animal pathogen with many virulence factors described. It targets native or adaptive immune responses. S. aureus has several mechanisms that allow the pathogen to prevent, or even hijack, this response to its advantage. Not only can the bacteria develop a resistance against antimicrobial proteins, they can also survive inside neutrophils. This is likely an important factor in persistent infections. In addition, various strains of S. aureus may posses some of the battery of toxins and enzymes and other products that enhance infectivity and bacterial survival and proliferation. Here, a combination of host’s cellular and humoral mechanisms comes into place. Antibodies specific against toxins and enzymes and other soluble products neutralize their activities while antibodies specific against cells and cellular components opsonize the targeted cells and enhance their phagocytosis. It thus seems very plausible to speculate that, in patients with chronic S. aureus infections, one or more defense pathways may not be activated or functional.
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