2021 Feb;590(7845):320-325.
doi: 10.1038/s41586-020-3035-9. Epub 2020 Dec 1.
A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate
- PMID: 33260195
- DOI: 10.1038/s41586-020-3035-9
Abstract
The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.
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https://pubmed.ncbi.nlm.nih.gov/33260195/
JOHAN NEYTS
research group Johan Neyts
Rega – Herestraat 49 – box 1043
3000 Leuven
Belgium
room: 08.A064tel: +32 16 32 18 93 or +32 16 37 90 20
contactJohan Neyts (CV) is full professor of virology at the University of Leuven, Belgium. He teaches virology at the medical school and at the school of dentistry. His lab has a long-standing expertise in the development of antiviral strategies and drugs against emerging and neglected viral infections (such as dengue and other flaviviruses, Chikungunya, enteroviruses, noroviruses, coronaviruses, HEV and rabies). His lab is also intensively involved in the development of antivirals against SARS-CoV2. A second focus of the lab is the development of novel vaccine technologies. To that end the yellow fever vaccine is being used as a vector. Using this technology the team developed a potent single shot SARS-CoV2 vaccine candidate. The PLLAV (Plasmid Launched Live Attenuated Virus) technology, also developed in his lab, allows to rapidly engineer highly thermostable vaccines against multiple viral pathogens. Johan Neyts is past president of the International Society for Antiviral Research (www.isar-icar.com). Four classes of antivirals discovered in his laboratory have been licensed to major pharmaceutical companies (two on HCV, one on dengue and one on rhino/enteroviruses). He published >500 papers in peer reviewed journals and has given ~230 invited lectures; he is regularly interviewed by lay-press. https://rega.kuleuven.be/cmt/jn/staff-1/staff/00014425
Batavia and KU Leuven join forces to accelerate development of highly promising COVID-19 vaccine candidate
Leiden, 3 December 2020 – KU Leuven, a leading research institution and one of the top 50 universities in the world and Batavia Biosciences, a contract development and manufacturing organization focused on delivering sustainable manufacturing solutions in the field of vaccines and oncology, today announce their partnership on the development of a vector based COVID-19 vaccine candidate.
The virology team at the KU Leuven Rega Institute for Medical Research, headed by Prof Dr Johan Neyts, has developed a SARS-CoV-2 vaccine candidate consisting of an attenuated vector carrying the SARS-CoV-2 spike immunogen. The vector is derived from the live-attenuated yellow fever vaccine (YF17D strain), which is a proven safe and effective vaccine, used worldwide to protect more than 500 million people against yellow fever.
The YF17D-SARS-CoV-2 vaccine candidate, tentatively named RegaVax, shows convincing pre-clinical immunogenicity and efficacy data in challenge studies, as recently published in Nature (Sanchez-Felipe et al., 2020). Based on this promising data the research group is now confident to start the next phase of development, heading towards preparation for clinical trials.
To support this activity, KU Leuven has partnered with Batavia Biosciences, a frontrunner in developing highly intensified and low-cost vaccine manufacturing processes. Batavia will leverage its vaccine development and manufacturing experience together with its high intensity HIP-Vax® manufacturing technology to develop a clinical manufacturing process for the vaccine candidate, deliver clinical product and prepare for large-scale commercial supply.
Prof Neyts (Head of the Virology research group at the KU Leuven Rega Institute) commented: “RegaVax is the only COVID-19 vaccine candidate based on the yellow fever vaccine. In preclinical models, for example with hamsters, one single dose appears to be highly efficient in protecting against infection with SARS-CoV-2. We hope that this vaccine, will, like the yellow fever vaccine on which it is based, provide, after a single dose, long-lasting protection against this coronavirus.”
Dr. Menzo Havenga (CEO, Batavia Biosciences) stated: “We are delighted to team up with the group of Prof Neyts as the preclinical data generated by the team at KU Leuven for this vaccine candidate look extremely promising.” Dr Christopher Yallop (COO, Batavia Biosciences) added: “Our HIP-Vax technology is ideally suited to develop and manufacture this vaccine rapidly and cost effectively and we are very much looking forward to work closely with the KU Leuven team to deliver the clinical product and help move this vaccine candidate to licensure.”
The partnership aims to deliver the clinical product and to commence clinical testing in 2021.
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