Immunogenicity, Lot Consistency, and Extended Safety of RVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2019 Sep 11

PMID 31505665

Citations 32

Authors

Scott A Halperin

Rituparna Das

Matthew T Onorato

Kenneth Liu

Jason Martin

Rebecca J Grant-Klein

Rick Nichols

Beth-Ann Coller

Frans A Helmond

Jakub K Simon

Affiliations

Soon will be listed here.

Abstract

Background: This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).

Methods: Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed.

Results: ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination.

Conclusions: Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development.

Clinical Trials Registration: NCT02503202.

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References

Qiu X, Fernando L, Alimonti J, Melito P, Feldmann F, Dick D . Mucosal immunization of cynomolgus macaques with the VSVDeltaG/ZEBOVGP vaccine stimulates strong ebola GP-specific immune responses. PLoS One. 2009; 4(5):e5547. PMC: 2678264. DOI: 10.1371/journal.pone.0005547. View

Kennedy S, Bolay F, Kieh M, Grandits G, Badio M, Ballou R . Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia. N Engl J Med. 2017; 377(15):1438-1447. PMC: 5705229. DOI: 10.1056/NEJMoa1614067. View

Marzi A, Robertson S, Haddock E, Feldmann F, Hanley P, Scott D . EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Science. 2015; 349(6249):739-42. PMC: 11040598. DOI: 10.1126/science.aab3920. View

Feldmann H, Jones S, Daddario-DiCaprio K, Geisbert J, Stroher U, Grolla A . Effective post-exposure treatment of Ebola infection. PLoS Pathog. 2007; 3(1):e2. PMC: 1779298. DOI: 10.1371/journal.ppat.0030002. View

Henao-Restrepo A, Camacho A, Longini I, Watson C, Edmunds W, Egger M . Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2016; 389(10068):505-518. PMC: 5364328. DOI: 10.1016/S0140-6736(16)32621-6. View

Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Moller P, Wagner R . Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol. 2004; 78(10):5458-65. PMC: 400370. DOI: 10.1128/jvi.78.10.5458-5465.2004. View

Marzi A, Ebihara H, Callison J, Groseth A, Williams K, Geisbert T . Vesicular stomatitis virus-based Ebola vaccines with improved cross-protective efficacy. J Infect Dis. 2011; 204 Suppl 3:S1066-74. PMC: 3203393. DOI: 10.1093/infdis/jir348. View

Mire C, Miller A, Carville A, Westmoreland S, Geisbert J, Mansfield K . Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates. PLoS Negl Trop Dis. 2012; 6(3):e1567. PMC: 3308941. DOI: 10.1371/journal.pntd.0001567. View

Huttner A, Agnandji S, Combescure C, Fernandes J, Bache E, Kabwende L . Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Lancet Infect Dis. 2018; 18(7):738-748. PMC: 6408946. DOI: 10.1016/S1473-3099(18)30165-8. View

10.

Agua-Agum J, Allegranzi B, Ariyarajah A, Aylward R, Blake I, Barboza P . After Ebola in West Africa--Unpredictable Risks, Preventable Epidemics. N Engl J Med. 2016; 375(6):587-96. DOI: 10.1056/NEJMsr1513109. View

11.

Agnandji S, Huttner A, Zinser M, Njuguna P, Dahlke C, Fernandes J . Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med. 2015; 374(17):1647-60. PMC: 5490784. DOI: 10.1056/NEJMoa1502924. View

12.

Marzi A, Engelmann F, Feldmann F, Haberthur K, Shupert W, Brining D . Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates. Proc Natl Acad Sci U S A. 2013; 110(5):1893-8. PMC: 3562844. DOI: 10.1073/pnas.1209591110. View

13.

WEIBEL R, STOKES Jr J, BUYNAK E, HILLEMAN M . Influence of age on clinical response to HPV-77 duck rubella vaccine. JAMA. 1972; 222(7):805-7. View

14.

Feldmann H, Geisbert T . Ebola haemorrhagic fever. Lancet. 2010; 377(9768):849-62. PMC: 3406178. DOI: 10.1016/S0140-6736(10)60667-8. View

15.

Marzi A, Feldmann H . Ebola virus vaccines: an overview of current approaches. Expert Rev Vaccines. 2014; 13(4):521-31. PMC: 4785864. DOI: 10.1586/14760584.2014.885841. View

16.

Juan-Giner A, Tchaton M, Jemmy J, Soumah A, Boum Y, Faga E . Safety of the rVSV ZEBOV vaccine against Ebola Zaire among frontline workers in Guinea. Vaccine. 2018; 37(48):7171-7177. DOI: 10.1016/j.vaccine.2018.09.009. View

17.

Halperin S, Arribas J, Rupp R, Andrews C, Chu L, Das R . Six-Month Safety Data of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein Vaccine in a Phase 3 Double-Blind, Placebo-Controlled Randomized Study in Healthy Adults. J Infect Dis. 2017; 215(12):1789-1798. PMC: 5853326. DOI: 10.1093/infdis/jix189. View

18.

Gunn B, Yu W, Karim M, Brannan J, Herbert A, Wec A . A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus. Cell Host Microbe. 2018; 24(2):221-233.e5. PMC: 6298217. DOI: 10.1016/j.chom.2018.07.009. View

19.

Heppner Jr D, Kemp T, Martin B, Ramsey W, Nichols R, Dasen E . Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. Lancet Infect Dis. 2017; 17(8):854-866. DOI: 10.1016/S1473-3099(17)30313-4. View

20.

Henao-Restrepo A, Longini I, Egger M, Dean N, Edmunds W, Camacho A . Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015; 386(9996):857-66. DOI: 10.1016/S0140-6736(15)61117-5. View