JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe

Selidji T Agnandji, Angela Huttner, Madeleine E Zinser, Patricia Njuguna, Christine Dahlke, José F Fernandes, Sabine Yerly, Julie-Anne Dayer, Verena Kraehling, Rahel Kasonta, Akim A Adegnika, Marcus Altfeld, Floriane Auderset, Emmanuel B Bache, Nadine Biedenkopf, Saskia Borregaard, Jessica S Brosnahan, Rebekah Burrow, Christophe Combescure, Jules Desmeules, Markus Eickmann, Sarah K Fehling, Axel Finckh, Ana Rita Goncalves, Martin P Grobusch, Jay Hooper, Alen Jambrecina, Anita L Kabwende, Gürkan Kaya, Domtila Kimani, Bertrand Lell, Barbara Lemaître, Ansgar W Lohse, Marguerite Massinga-Loembe, Alain Matthey, Benjamin Mordmüller, Anne Nolting, Caroline Ogwang, Michael Ramharter, Jonas Schmidt-Chanasit, Stefan Schmiedel, Peter Silvera, Felix R Stahl, Henry M Staines, Thomas Strecker, Hans C Stubbe, Benjamin Tsofa, Sherif Zaki, Patricia Fast, Vasee Moorthy, Laurent Kaiser, Sanjeev Krishna, Stephan Becker, Marie-Paule Kieny, Philip Bejon, Peter G Kremsner, Marylyn M Addo, Claire-Anne Siegrist
New England Journal of Medicine 2016 April 28, 374 (17): 1647-60
25830326

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa.

METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo.

RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants.

CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
25830326
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"