A Surprising Outcome in a Staph Vaccine Trial

Patients who received an investigational Staphylococcus aureus vaccine before cardiothoracic surgery showed significantly increased rates of postoperative multiorgan failure and death from staphylococcal infections.

Given increasing problems with antibiotic resistance in Staphylococcus aureus, new approaches to prevent staphylococcal infections are needed. In recent studies, a novel vaccine candidate (V710) based on a highly conserved S. aureus iron surface determinant was found to be protective in animal studies and highly immunogenic after a single dose in healthy volunteers. Now, in a manufacturer-sponsored, multinational, multicenter, phase IIb/III trial, researchers have assessed the vaccine's efficacy and safety in preventing serious S. aureus infections in adults who were about to undergo cardiothoracic surgery.

A total of 7983 participants had been vaccinated with either V710 or placebo when the data safety monitoring committee recommended study termination. The V710 vaccine was immunogenic and did induce increased levels of antistaphylococcal antibodies with opsonophagocytic activity. However, the incidence of the S. aureus bacteremia and deep surgical site infections was similar between vaccine and placebo recipients, and the incidence of postoperative multiorgan failure was significantly increased in vaccine recipients. In addition, the mortality rate among patients who developed a postoperative S. aureus infection was significantly higher for vaccine recipients than for placebo recipients.

Comment

The authors note that this study does not establish a causal relationship between the V710 vaccine and worse clinical outcomes in patients with staphylococcal infections, and a clear mechanism for such an effect is not clear. However, paradoxical reactions leading to more-severe clinical disease have been seen previously with other vaccines. The present findings highlight the need for a much deeper understanding of the humoral and cellular immune response to S. aureus before a safe and effective staphylococcal vaccine can be developed.

Reviewing Author

Richard T. Ellison III, MD

Disclosures

Consult/Advisory BoardAcurx Pharmaceuticals, LLC;

Grant/Research SupportDoctors Company Foundation, Massachusetts Department of Public Health

Richard T. Ellison III, MD

Disclosures

Consult/Advisory BoardAcurx Pharmaceuticals, LLC;

Grant/Research SupportDoctors Company Foundation, Massachusetts Department of Public Health

Citation(s):

Fowler VG Jr et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: A randomized trial. JAMA 2013 Apr 3; 309:1368.