Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick

Abstract

Importance: Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick.

Objective: To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus.

Design and setting: Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014.

Interventions: The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa.

Results: The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected.

Conclusions and relevance: It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.

Figure 1. Transient Fever and Low-Level Viremia Postvaccination With VSVΔG-ZEBOV

The VSVΔG-ZEBOV vaccine was made up of a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. Prevaccination blood samples were not available. The needlestick occurred 43 hours before vaccination. A, The dashed horizontal line indicates 38°C. B, The number of polymerase chain reaction cycles required to amplify and detect the target RNA is known as the threshold cycle; thus, a lower threshold cycle value indicates that a higher concentration of target template is present. The dashed horizontal line indicates the limit of detection. Further details of real-time reverse transcription–polymerase chain reaction appear in the eMethods section in the Supplement.

Figure 2. Immune Responses From Assays Conducted on Days 2, 4, 9, 17, and 34

A, Determined by phenotyping using multicolor flow cytometry. B, Plasmablast response determined with multicolor flow cytometry.^, The plasmablasts are CD3⁻/CD20^−/low/CD19/CD27^high/CD38^high; the B cells are CD3⁻/CD20/CD19. C, The antibody response to Ebola glycoprotein is shown. Antibody to viral matrix protein 40 IgG was not detectable at all 5 time points assayed (not shown). D, Production of cytokines (INF-γ, tumor necrosis factor, IL-2, or some combination) by glycoprotein-specific T cells after peptide stimulation as measured by intracellular cytokine staining.

Figure 3. Levels of 48 Detected Plasma Cytokines, Chemokines, and Growth Factors After Vaccination

Day 2 was the day after vaccination. The numbers shown within each cell are fold increases (or decreases) relative to the level at day 34. The proteins were detected by antibody-bound beads and quantitated using a Luminex instrument. All protein levels were normalized to day 34 levels because a prevaccination plasma sample was not available. Fifteen additional cytokines were undetectable (eTable in the Supplement). BDNF indicates brain-derived neurotrophic factor; bNGF, β-nerve growth factor; EGF, epidermal growth factor; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HGF, hepatocyte growth factor; LIF, Leukemia inhibitory factor; MCP, monocyte chemotactic protein; MIP, macrophage inflammatory protein; PAI-1, plasminogen activator inhibitor 1; PDGF-BB, platelet-derived growth factor BB; RA, receptor antagonist; RANTES, regulated on activation normal T cell expressed and secreted; sCD40L, soluble CD40 ligand; SCF, stem cell factor; SDF-1α, stromal cell-derived factor 1α; sICAM-1, soluble intercellular adhesion molecule 1; sVCAM-1, soluble vascular adhesion molecule 1; TGF, transforming growth factor; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor–related apoptosis-inducing ligand; VEGF, vascular endothelial growth factor.