YF17D-vectored Ebola Vaccine Candidate Protects Mice Against Lethal Surrogate Ebola and Yellow Fever Virus Challenge

Overview

Journal NPJ Vaccines

Date 2023 Jul 11

PMID 37433816

Authors

Viktor Lemmens

Lara Kelchtermans

Sarah Debaveye

Winston Chiu

Thomas Vercruysse

Ji Ma

Hendrik Jan Thibaut

Johan Neyts

Lorena Sanchez-Felipe

Kai Dallmeier

Affiliations

Soon will be listed here.

Abstract

Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV GP-specific antibodies and cellular immune responses, that protected against lethal infection using EBOV GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protected Ifnar mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of the 2022 outbreak in Uganda.

Citing Articles

Immunogenicity and Protective Efficacy of Aerosolized Live-Attenuated Yellow Fever 17D Vaccine in Mice.

Zhu F, Sun M, Zhao S, Qin C, Wang J, Deng Y Vaccines (Basel). 2024; 12(8).

PMID: 39203982 PMC: 11360090. DOI: 10.3390/vaccines12080856.

Parallel Multifactorial Process Optimization and Intensification for High-Yield Production of Live YF17D-Vectored Zika Vaccine.

Gobel S, Kazemi O, Ma J, Jordan I, Sandig V, Paulissen J Vaccines (Basel). 2024; 12(7).

PMID: 39066393 PMC: 11281342. DOI: 10.3390/vaccines12070755.

References

Bausch D . The need for a new strategy for Ebola vaccination. Nat Med. 2021; 27(4):580-581. DOI: 10.1038/s41591-021-01313-w. View

Li L, Liesenborghs L, Wang L, Lox M, Bright Yakass M, Jansen S . Biodistribution and environmental safety of a live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Mol Ther Methods Clin Dev. 2022; 25:215-224. PMC: 8925082. DOI: 10.1016/j.omtm.2022.03.010. View

Whitt M . Generation of VSV pseudotypes using recombinant ΔG-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines. J Virol Methods. 2010; 169(2):365-74. PMC: 2956192. DOI: 10.1016/j.jviromet.2010.08.006. View

Muller U, Steinhoff U, Reis L, Hemmi S, Pavlovic J, Zinkernagel R . Functional role of type I and type II interferons in antiviral defense. Science. 1994; 264(5167):1918-21. DOI: 10.1126/science.8009221. View

Huttner A, Dayer J, Yerly S, Combescure C, Auderset F, Desmeules J . The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2015; 15(10):1156-1166. PMC: 6624136. DOI: 10.1016/S1473-3099(15)00154-1. View

Marzi A, Kercher L, Marceau J, York A, Callsion J, Gardner D . Stat1-Deficient Mice Are Not an Appropriate Model for Efficacy Testing of Recombinant Vesicular Stomatitis Virus-Based Filovirus Vaccines. J Infect Dis. 2015; 212 Suppl 2:S404-9. PMC: 4564544. DOI: 10.1093/infdis/jiv188. View

Carnino L, Vetter P, Peyraud N, Aebischer-Perone S, Chappuis F, Huttner A . Feasibility and safety of rVSV-ZEBOV vaccination of humanitarian health workers against Ebola virus disease: an observational study. J Travel Med. 2021; 28(8). DOI: 10.1093/jtm/taab086. View

Ferrara F, Temperton N . Pseudotype Neutralization Assays: From Laboratory Bench to Data Analysis. Methods Protoc. 2019; 1(1). PMC: 6526431. DOI: 10.3390/mps1010008. View

Agnandji S, Massinga Loembe M . Ebola vaccines for mass immunisation in affected regions. Lancet Infect Dis. 2021; 22(1):8-10. DOI: 10.1016/S1473-3099(21)00226-7. View

10.

Marchevsky R, Mariano J, Ferreira V, Almeida E, Cerqueira M, Carvalho R . Phenotypic analysis of yellow fever virus derived from complementary DNA. Am J Trop Med Hyg. 1995; 52(1):75-80. DOI: 10.4269/ajtmh.1995.52.75. View

11.

Meier K, Gardner C, Khoretonenko M, Klimstra W, Ryman K . A mouse model for studying viscerotropic disease caused by yellow fever virus infection. PLoS Pathog. 2009; 5(10):e1000614. PMC: 2749449. DOI: 10.1371/journal.ppat.1000614. View

12.

Sanchez-Felipe L, Vercruysse T, Sharma S, Ma J, Lemmens V, Van Looveren D . A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature. 2020; 590(7845):320-325. DOI: 10.1038/s41586-020-3035-9. View

13.

. Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Wkly Epidemiol Rec. 2017; 92(16):193-204. View

14.

Mate S, Kugelman J, Nyenswah T, Ladner J, Wiley M, Cordier-Lassalle T . Molecular Evidence of Sexual Transmission of Ebola Virus. N Engl J Med. 2015; 373(25):2448-54. PMC: 4711355. DOI: 10.1056/NEJMoa1509773. View

15.

Huber C, Finelli L, Stevens W . The Economic and Social Burden of the 2014 Ebola Outbreak in West Africa. J Infect Dis. 2018; 218(suppl_5):S698-S704. DOI: 10.1093/infdis/jiy213. View

16.

Bredenbeek P, Molenkamp R, Spaan W, Deubel V, Marianneau P, Salvato M . A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins. Virology. 2006; 345(2):299-304. PMC: 1388090. DOI: 10.1016/j.virol.2005.12.001. View

17.

Ma J, Bright Yakass M, Jansen S, Malengier-Devlies B, Van Looveren D, Sanchez-Felipe L . Live-attenuated YF17D-vectored COVID-19 vaccine protects from lethal yellow fever virus infection in mouse and hamster models. EBioMedicine. 2022; 83:104240. PMC: 9419561. DOI: 10.1016/j.ebiom.2022.104240. View

18.

Seligman S . Risk groups for yellow fever vaccine-associated viscerotropic disease (YEL-AVD). Vaccine. 2014; 32(44):5769-75. DOI: 10.1016/j.vaccine.2014.08.051. View

19.

Diallo B, Sissoko D, Loman N, Bah H, Bah H, Worrell M . Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days. Clin Infect Dis. 2016; 63(10):1353-1356. PMC: 5091350. DOI: 10.1093/cid/ciw601. View

20.

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