Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2022 Mar 22

PMID 35313504

Authors

Li-Hsin Li

Laurens Liesenborghs

Lanjiao Wang

Marleen Lox

Michael Bright Yakass

Sander Jansen

Ana Lucia Rosales Rosas

Xin Zhang

Hendrik Jan Thibaut

Dirk Teuwen

Johan Neyts

Leen Delang

Kai Dallmeier

Affiliations

Soon will be listed here.

Abstract

New platforms are needed for the design of novel prophylactic vaccines and advanced immune therapies. Live-attenuated yellow fever vaccine YF17D serves as a vector for several licensed vaccines and platform for novel candidates. On the basis of YF17D, we developed an exceptionally potent COVID-19 vaccine candidate called YF-S0. However, use of such live RNA viruses raises safety concerns, such as adverse events linked to original YF17D (yellow fever vaccine-associated neurotropic disease [YEL-AND] and yellow fever vaccine-associated viscerotropic disease [YEL-AVD]). In this study, we investigated the biodistribution and shedding of YF-S0 in hamsters. Likewise, we introduced hamsters deficient in signal transducer and activator of transcription 2 (STAT2) signaling as a new preclinical model of YEL-AND/AVD. Compared with YF17D, YF-S0 showed improved safety with limited dissemination to brain and visceral tissues, absent or low viremia, and no shedding of infectious virus. Considering that yellow fever virus is transmitted by mosquitoes, any inadvertent exposure to the live recombinant vector via mosquito bites is to be excluded. The transmission risk of YF-S0 was hence compared with readily transmitting YF-Asibi strain and non-transmitting YF17D vaccine, with no evidence for productive infection of mosquitoes. The overall favorable safety profile of YF-S0 is expected to translate to other vaccines based on the same YF17D platform.

Citing Articles

Development of a fully automated chemiluminescent immunoassay for the quantitative and qualitative detection of antibodies against African swine fever virus p72.

Wang L, Li D, Zeng D, Wang S, Wu J, Liu Y Microbiol Spectr. 2024; 12(10):e0080924.

PMID: 39145655 PMC: 11448198. DOI: 10.1128/spectrum.00809-24.

Comparative Biodistribution Study of Baculoviral and Adenoviral Vector Vaccines against SARS-CoV-2.

Lee H, Chun J, Kim S, Aleksandra N, Lee C, Yoon D J Microbiol Biotechnol. 2023; 34(1):185-191.

PMID: 37830223 PMC: 10840461. DOI: 10.4014/jmb.2308.08042.

YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge.

Lemmens V, Kelchtermans L, Debaveye S, Chiu W, Vercruysse T, Ma J NPJ Vaccines. 2023; 8(1):99.

PMID: 37433816 PMC: 10336040. DOI: 10.1038/s41541-023-00699-7.

Live-attenuated YF17D-vectored COVID-19 vaccine protects from lethal yellow fever virus infection in mouse and hamster models.

Ma J, Bright Yakass M, Jansen S, Malengier-Devlies B, Van Looveren D, Sanchez-Felipe L EBioMedicine. 2022; 83:104240.

PMID: 36041265 PMC: 9419561. DOI: 10.1016/j.ebiom.2022.104240.

References

Danet L, Beauclair G, Berthet M, Moratorio G, Gracias S, Tangy F . Midgut barriers prevent the replication and dissemination of the yellow fever vaccine in Aedes aegypti. PLoS Negl Trop Dis. 2019; 13(8):e0007299. PMC: 6709925. DOI: 10.1371/journal.pntd.0007299. View

Garcia-Beltran W, Lam E, St Denis K, Nitido A, Garcia Z, Hauser B . Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell. 2021; 184(9):2372-2383.e9. PMC: 7953441. DOI: 10.1016/j.cell.2021.03.013. View

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

de Lataillade L, Vazeille M, Obadia T, Madec Y, Mousson L, Kamgang B . Risk of yellow fever virus transmission in the Asia-Pacific region. Nat Commun. 2020; 11(1):5801. PMC: 7669885. DOI: 10.1038/s41467-020-19625-9. View

Pulendran B . Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology. Nat Rev Immunol. 2009; 9(10):741-7. DOI: 10.1038/nri2629. View

Ma H, Lai C, Chiu N, Lee P . Adverse events following immunization with the live-attenuated recombinant Japanese encephalitis vaccine (IMOJEV®) in Taiwan, 2017-18. Vaccine. 2020; 38(33):5219-5222. DOI: 10.1016/j.vaccine.2020.06.008. View

P Monath T, Liu J, Kanesa-Thasan N, Myers G, Nichols R, Deary A . A live, attenuated recombinant West Nile virus vaccine. Proc Natl Acad Sci U S A. 2006; 103(17):6694-9. PMC: 1436023. DOI: 10.1073/pnas.0601932103. View

Kum D, Mishra N, Vrancken B, Thibaut H, Wilder-Smith A, Lemey P . Limited evolution of the yellow fever virus 17d in a mouse infection model. Emerg Microbes Infect. 2019; 8(1):1734-1746. PMC: 6896426. DOI: 10.1080/22221751.2019.1694394. View

Cai C, Peng Y, Shen E, Huang Q, Chen Y, Liu P . A comprehensive analysis of the efficacy and safety of COVID-19 vaccines. Mol Ther. 2021; 29(9):2794-2805. PMC: 8342868. DOI: 10.1016/j.ymthe.2021.08.001. View

10.

Cromer D, Steain M, Reynaldi A, Schlub T, Wheatley A, Juno J . Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe. 2021; 3(1):e52-e61. PMC: 8592563. DOI: 10.1016/S2666-5247(21)00267-6. View

11.

Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y . Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. N Engl J Med. 2021; 385(23):2132-2139. PMC: 8531986. DOI: 10.1056/NEJMoa2110737. View

12.

Heinz F, Stiasny K . Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action. NPJ Vaccines. 2021; 6(1):104. PMC: 8368295. DOI: 10.1038/s41541-021-00369-6. View

13.

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

14.

Biedenbender R, Bevilacqua J, Gregg A, Watson M, Dayan G . Phase II, randomized, double-blind, placebo-controlled, multicenter study to investigate the immunogenicity and safety of a West Nile virus vaccine in healthy adults. J Infect Dis. 2010; 203(1):75-84. PMC: 3086439. DOI: 10.1093/infdis/jiq003. View

15.

P Monath T . Review of the risks and benefits of yellow fever vaccination including some new analyses. Expert Rev Vaccines. 2012; 11(4):427-48. DOI: 10.1586/erv.12.6. View

16.

Neukirch L, Fougeroux C, Andersson A, Holst P . The potential of adenoviral vaccine vectors with altered antigen presentation capabilities. Expert Rev Vaccines. 2020; 19(1):25-41. DOI: 10.1080/14760584.2020.1711054. View

17.

Barrett A, Teuwen D . Yellow fever vaccine - how does it work and why do rare cases of serious adverse events take place?. Curr Opin Immunol. 2009; 21(3):308-13. DOI: 10.1016/j.coi.2009.05.018. View

18.

Quaresma J, Pagliari C, Medeiros D, Duarte M, Vasconcelos P . Immunity and immune response, pathology and pathologic changes: progress and challenges in the immunopathology of yellow fever. Rev Med Virol. 2013; 23(5):305-18. DOI: 10.1002/rmv.1752. View

19.

Dallmeier K, Meyfroidt G, Neyts J . COVID-19 and the intensive care unit: vaccines to the rescue. Intensive Care Med. 2021; 47(7):786-789. PMC: 8143986. DOI: 10.1007/s00134-021-06414-1. View

20.

Guy B, Noriega F, Ochiai R, LAzou M, Delore V, Skipetrova A . A recombinant live attenuated tetravalent vaccine for the prevention of dengue. Expert Rev Vaccines. 2017; 16(7):1-13. DOI: 10.1080/14760584.2017.1335201. View