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Data suggest feasibility of vaccine to reduce severity 
of S. aureus

Issue: October 2012

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Recent study findings from a collaboration between researchers at University of Maryland and Integrated Biotherapeutics Inc. support the development of a multivalent toxin-based Staphylococcus aureus vaccine for the reduction of severity of invasive S. aureus infection.

“Although S. aureus is a common cause of both hospital- and community-acquired infections, efforts to make a prophylactic vaccine have been challenging,” study researcher Mary-Claire Roghmann, MD, MS, told Infectious Disease News. “Our study suggests that a different approach to S. aureus vaccine development could be entertained. Rather than prevent the occurrence of invasive infections, a vaccine could reduce the risk of severe infections and still make a significant public health impact.”

Currently, there is no FDA-approved vaccine to prevent S. aureus infections. Roghmann and colleagues set out to examine data on 100 adults presenting with S. aureus infection across four Baltimore hospitals from 2009 to 2011. Researchers obtained serum samples before or at the time patients presented with the bacteremia to assess their immunoglobulin G (IgG) antibody levels to 11 known S. aureus exotoxins. Polymerase chain reaction was used to test bacterial isolates for the genes encoding S. aureus exotoxins.

Of the 100 eligible patients in the study, 27 developed sepsis. Compared with patients without sepsis, those with sepsis had lower antibody levels against prominent S. aureus toxins, including alpha hemolysin (P<.01), delta hemolysin (P<.01), LukF-PV (P=.02) and LukS-PV (P=.01), SEA (P=.01), SEC-1 (P=.01) and SED (P=.01). Patients with sepsis also had lower antibody levels against PSM-alpha 3 (P=.01). Total IgG levels were significantly lower in patients with sepsis (P=.02).

After adjusting for total IgG levels, the researchers found that sepsis risk was significantly lower in patients with higher levels of IgG against toxins alpha hemolysin, delta hemolysin, SEC-1 and PSM-alpha 3. Results also indicated that higher levels of antibodies against PVL and SEB toxins lowered sepsis risk only when PVL or SEB genes were present in the infected isolate.

“Over 19 superantigens are variably expressed in different S. aureus clinical isolates, posing a challenge for the inclusion of all superantigens in a multivalent S. aureus vaccine. However, it may be feasible to include only a few of the most frequently expressed toxins.” the researchers wrote. “Taken together, our results support our therapeutic rationale for passive or active immunization with a multivalent vaccine, which elicits high antibody levels against selected toxins for the reduction of severity of invasive S. aureus infections.”

• Adhikari RP. J Infec Dis. 2012;206:915-923.

Disclosures: Adhikari, Aman, Karauzum and Sarwar are employed by Integrated BioTherapeutics Inc. Chen is the principal investigator of a NIH-funded phase 1 study of a staphylococcal enterotoxin B vaccine co-sponsored by Integrated BioTherapeutics Inc. The other researchers report no relevant financial disclosures.