Effect of an Investigational Vaccine for Preventing Staphylococcus aureus Infections After Cardiothoracic Surgery

Abstract

NFECTIONS WITH STAPHYLOCOCCUS aureus following median sternotomy cause substantial morbidity and mortality. 1-3 A safe vaccine that provides protection against a majority of S aureus strains during the postoperative period would address an important unmet medical need. 4,5 A novel vaccine candidate (V710; Merck Sharp & Dohme Corp) containing the highly conserved S aureus 0657nI iron surface determinant B (IsdB) was protective in animal challenge models 6-8 and immunogenic within 14 days after a single dose of either an adjuvanted or nonadjuvanted formulation in healthy volunteers. 9,10 Antibody response to V710 was similar in younger and older partici-For editorial comment see p 1408.

Naturally occurring IgG antibody levels to theStaphylococcus aureusprotein IsdB in humans

“…9 The potential use of this antigen as a component of a vaccine for prevention of S. aureus disease has been previously described. 9,15 However, as a stand-alone vaccine (V710), protection was not observed in a clinical efficacy trial among cardiac surgery patients, 21 despite a significant increase in IsdB antibody titers in the V710 vaccinated patients. Although the IsdB specific with the hospital controls (p = 0.05).…”

“…Although colonization data were not collected in the current study, in the Merck V710 (Protocol 003) trial, nasal colonization data was collected at day of vaccination. 21 Among Protocol 003 patients, it was observed that those who were nasally colonized with S. aureus, had baseline anti-IsdB antibody response was stimulated by V710, it remains unclear which immune mechanisms are critical to mediate clinical efficacy against S. aureus. In recently reported data, protection mediated via IsdB vaccination in mice was dependent on the T-cell (CD4+) response to the vaccine.…”

“…24,29,30 The assay has been extensively characterized and used to support multiple Merck clinical trials. 20,21,31 Briefly, a truncated form of IsdB (aa 42-486), containing the two NEAT domains of IsdB (aa140-462) (750 µg) was covalently bound to 9.6 × 10 6 Radix maleimide-modified microspheres (Radix) via a C-terminal cysteine residue at room temperature. Microspheres were washed with phosphate buffered saline (PBS)/0.05% Tween-20 (Sigma-Aldrich) and then quenched with 1M N-acetyl-l-cysteine for 2 h at room temperature.…”

“…Antibody titers were no different between V710 patients who contracted S. aureus infections vs. those who did not. 21 To determine if the vaccine target antigen was conserved in the S. aureus strains from the trial, the isdB gene was analyzed in > 250 isolates, and all contained the gene encoding IsdB. A representative subset was examined for IsdB expression, and expression was confirmed in vitro under iron-restricted conditions (data not shown).…”

Superantigens of a superbug: Major culprits ofStaphylococcus aureusdisease?

“…In fact clinical results suggests that vaccination with ISdB may have worsened the outcome of S. aureus infection as vaccinated individuals showed significantly higher rate of multi-organ failure. 5 A recent study also suggested a deleterious effect on subsequent S. aureus infection in rabbits vaccinated with a crude surface antigen preparation. 6 These findings reflect the complex nature of S. aureus interactions with the host and challenges facing vaccine development for this pathogen.…”