title: Mortality among recipients of the Merck V710 Staphylococcus aureus vaccine after postoperative S. aureus infections: an analysis of possible contributing host factors.
abstract: In a blinded randomized trial, preoperative receipt of the Merck V710 Staphylococcus aureus vaccine was associated with a higher mortality rate than placebo in patients who later developed postoperative S. aureus infections. Of the tested patients, all 12 V710 recipients (but only 1 of 13 placebo recipients) with undetectable serum IL2 levels prior to vaccination and surgery died after postoperative S. aureus infection. The coincidence of 3 factors (low prevaccination IL-2 levels, receipt of V710, and postoperative S. aureus infection) appeared to substantially increase mortality in our study population after major cardiothoracic surgery. Furthermore, 9 of the 10 V710 recipients with undetectable preoperative IL17a levels and postoperative S. aureus infections died. Although the current study is hypothesis-generating and the exact pathophysiology remains speculative, these findings raise concern that immune predispositions may adversely impact the safety and efficacy of staphylococcal vaccines actively under development. The potential benefits of an effective vaccine against S. aureus justify continued but cautious pursuit of this elusive goal.
authors.affiliation: a Merck Research Laboratories ; West Point , PA USA.
authors.forename: Tessie B
authors.initials: TB
authors.lastname: McNeely
authors.forename: Najaf A
authors.initials: NA
authors.lastname: Shah
authors.forename: Arthur
authors.initials: A
authors.lastname: Fridman
authors.forename: Amita
authors.initials: A
authors.lastname: Joshi
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Hartzel
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Keshari
authors.forename: Florea
authors.initials: F
authors.lastname: Lupu
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
mesh_terms: D016207:Cytokines / Q000097:blood; D006801:Humans; D011183:Postoperative Complications / Q000401:mortality*; D013203:Staphylococcal Infections / Q000276:immunology / Q000401:mortality*; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014611:Vaccination
chemical_list: D016207:Cytokines; D013209:Staphylococcal Vaccines; C579630:V710 vaccine
keywords: CMI, Cell mediated immunity; IL, interleukin; Ig, immunoglobulin; IsdB, iron-regulated surface determinant B; LOD, limit of detection; S. aureus; Th, T helper; V710 vaccine; interleukins; original antigenic sin; postoperative infection