Infectious Disease

Researchers find targets for monoclonal antibodies in S. aureus

March 25, 2021

2 min read

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Source:

Bennett M. et al. Abstract 31. Presented at: St. Jude / PIDS Research Conference on Pediatric Infectious Diseases; March 4-6, 2021 (virtual meeting).

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At the time of publication, Healio was unable to confirm any relevant financial information.

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Monoclonal antibodies isolated from children with invasive staphylococcal aureus were able to perform broad neutralization against distantly related variants of the two-component leukotoxin LukAB, researchers reported.

“LukAB is critical to the targeting and killing of human neutrophils by S. aureus and is abundantly produced as part of an invasive human infection.” Monique Bennett, PhD, a junior faculty member in the Department of Pediatric Infectious Diseases at Vanderbilt University Medical Center, and colleagues reported. “LukAB is unique among the S. aureus cytotoxins in that it exists in distant form through distantly related strains of clinically relevant S. aureus.”

The researchers said they isolated B cells from children with invasive S. aureus infections, including bacteremia or acute hematogenous osteomyelitis.

After Epstein-Barr virus transformation, cell supernatants were screened for LukAB binding and selected to generate monoclonal hybridomas. The monoclonal antibodies were examined for their binding and neutralization function by in vitro cytotoxicity tests, and neutrophils HL-60 cells were cultured in the presence of human monoclonal antibodies and various allelic variants of LukAB.

There were 34 different human anti-LukAB monoclonal antibodies raised by three children with invasive S. aureus, the authors reported. Of these, 22% were isolated after infection with a strain of the clonal complex (CC) 8, which was consistent with the USA300 epidemic clone, while 78% were raised against CC5 strains.

They reported that all monoclonal antibodies neutralized LukAB from the same clonal complex as the infecting isolate. 23 also showed neutralization against other allele variants.

Seven monoclonal antibodies were able to comprehensively and effectively neutralize LukAB variants from clinically relevant tested clonal complexes – CC8, CC30, CC45, CC75, CC1, CC5 and CC398.

“We found strong evidence of a conserved target (or targets) for antibody-mediated toxin neutralization in various S. aureus strains,” the authors wrote. “This provides additional support for this toxin as a target of intervention as some previous vaccination attempts have likely been unsuccessful due to activity against a narrow subset of circulating S. aureus strains.”

S. aureus is one of the most common causes of superficial and invasive infections in children and adults. In the late 1990s, community-based MRSA became a major driver of infection in otherwise healthy individuals.

The development of novel antibiotics against S. aureus and especially against MRSA has been a focus of pharmaceutical companies in recent years and has been largely successful. However, developing antibody-based therapeutics and ultimately an S. aureus vaccine to prevent invasive infections has been much more difficult. There are several reasons for this, including the complex interaction of S. aureus as part of the normal human microbiome, as well as wide variation between S. aureus isolates.

Understanding how humans develop immunity to S. aureus may be key to solving the mystery of how effective S. aureus therapeutics and vaccines can be developed. The development of these therapies has the potential to significantly improve the quality of life of people with recurrent MRSA infections and potentially be life-saving for people at high risk for invasive infections, including people with central lines, people on hemodialysis, and people with other immunocompromised diseases.

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James Wood, MD, MSCI

S. aureus is one of the most common causes of superficial and invasive infections in children and adults. In the late 1990s, community-based MRSA became a major driver of infection in otherwise healthy individuals.

The development of novel antibiotics against S. aureus and especially against MRSA has been a focus of pharmaceutical companies in recent years and has been largely successful. However, developing antibody-based therapeutics and ultimately an S. aureus vaccine to prevent invasive infections has been much more difficult. There are several reasons for this, including the complex interaction of S. aureus as part of the normal human microbiome, as well as wide variation between S. aureus isolates.

Understanding how humans develop immunity to S. aureus may be key to solving the mystery of how effective S. aureus therapeutics and vaccines can be developed. The development of these therapies has the potential to significantly improve the quality of life of people with recurrent MRSA infections and potentially be life-saving for people at high risk for invasive infections, including people with central lines, people on hemodialysis, and people with other immunocompromised diseases.

James Wood, MD, MSCI

Assistant Professor of Pediatrics

Indiana University School of Medicine

Disclosure: Wood does not report any relevant financial information.

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