Naturally occurring IgG antibody levels to the Staphylococcus aureus protein IsdB in humans

Abstract

Staphylococcus aureus is a well-recognized, clinically important cause of nosocomial infections, and as such, a vaccine to prevent S. aureus infections would be an important achievement. A Phase IIB/III study of V710, a vaccine containing iron-regulated surface determinant B (IsdB), demonstrated significant sero-conversion rates in cardiovascular surgery patients following a single pre-surgery immunization. However, the vaccine was not efficacious in preventing bacteremia or deep sternal wound infection post-surgery, thus raising the possibility that IsdB might not be available for immune recognition during infection. The purpose of the work described herein was to evaluate and quantify the naturally occurring anti-IsdB levels at baseline and over time during infection, to understand whether IsdB is expressed during a S. aureus infection in hospitalized non-vaccinated patients. We evaluated baseline and follow-up titers in 3 populations: (1) healthy subjects, (2) hospitalized patients with non-S. aureus infections, and (3) hospitalized patients with S. aureus infections. Baseline anti-IsdB levels generally overlapped between the 3 groups, but were highly variable within each group. In healthy subjects, baseline and follow-up levels were highly correlated (Spearman's rho = 0.93), and the geometric mean fold-rise (GMFR) in anti-IsdB levels between study entry and last value was 0.9-fold (95% confidence interval (CI): 0.8 to 1.0 ; p = 0.09), showing no trend over time. The convalescent GMFR in anti-IsdB levels from baseline was 1.7-fold (95% CI: 1.3 to 2.2, p = 0.0008) during S. aureus infection, significantly different from the 1.0-fold GMFR (95% CI: 0.9–1.2, p = 0.60) in non-S. aureus infection, p = 0.005. Additionally, S. aureus isolates (51) obtained from the hospitalized patient group expressed the IsdB protein in vitro. Collectively, these data suggest that IsdB expression levels rise substantially following infection with S. aureus, but not with other pathogens, and IsdB is likely well-conserved across S. aureus strains.

Keywords: :

• S. aureus infection
• IsdB
• antibody levels
• healthy subjects
• hospitalized patients

Disclosure of Potential Conflicts of Interest

This analysis was supported by Merck and Co., Inc. JKZ, ME, MR, NK, TM, SSS, ASA, and JMA are current or former employees of Merck Sharp and Dohme and may own stock and/or stock options in the company. BNK and DDA were consultants for Merck.

Acknowledgments

All authors are responsible for the work described in this paper, and they contributed to the conception, data interpretation, and drafting of the manuscript and/or revising the manuscript for important intellectual content. All authors provided final approval of the version to be published.

Merck Sharp and Dohme Corp., a subsidiary of Merck and Co., Inc. funded this study.

The authors thank Jennifer Pawlowski and Kim Strohmaier (Merck Sharp and Dohme Corp.) for their assistance with the preparation and submission of this manuscript. The authors also thank Jonathan Hartzel for assistance with clinical statistics from the Merck V710 Protocol 003 clinical trial.

Supplemental Materials

Supplemental materials may be found here: www.landesbioscience.com/journals/vaccines/article/25253