Journal Article

A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate

Coelmont, Lotte, Arkalagud Javarappa, Mahadesh Prasad, Cawthorne, Christopher, De Keyzer, Carolien, Quaye, Osbourne, Teuwen, Dirk E., van Driel, Nikki, Boudewijns, Robbert, Van Looveren, Dominique, Schols, Dominique, Matthijnssens, Jelle, Bogers, Willy, Verschoor, Ernst, Neyts, Johan, Rasulova, Madina, Jansen, Sander, Kiemenyi-Kayere, Gwendoline, Ma, Ji, Yakass, Michael Bright, Seldeslachts, Laura, Jan Thibaut, Hendrik, Verstrepen, Babs E., Li, Li-Hsin, Zhang, Xin, Mishra, Niraj, Vande Velde, Greetje, Sharma, Sapna, Heylen, Elisabeth, Kuiken, Thijs, Kaptein, Suzanne J. F., Dallmeier, Kai, Lemmens, Viktor, Vercruysse, Thomas, Wang, Zhongde, Liesenborghs, Laurens, Sanchez-Felipe, Lorena, Weynand, Birgit, Opdenakker, Ghislain, ter Horst, Sebastiaan, Van Laere, Koen, Deboutte, Ward, Malengier-Devlies, Bert, Debaveye, Sarah, Matthys, Patrick, Bervoets, Lindsey, Böszörményi, Kinga P., Vandermeulen, Corinne, Vergote, Valentijn

2021

Overview

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 response 1 . 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 model 2 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. A candidate vaccine against SARS-CoV-2 that uses the yellow fever 17D live-virus vector is highly efficacious and displays a favourable safety profile in Syrian hamster, mouse and cynomolgus macaque models.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/1 / 13/106 / 13/109 / 13/21 / 13/31 / 13/44 / 13/51 / 14 / 14/19 / 14/63 / 38/23 / 38/39 / 59 / 631/250/590/1867 / 631/326/596/4130 / 692/699/255/2514 / Animal models / Animals / Antibodies / Antigens / Confidence intervals / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - adverse effects / COVID-19 Vaccines - genetics / COVID-19 Vaccines - immunology / Cricetinae / Disease Models, Animal / Emergency response / Female / Fever / Genetic Vectors - genetics / Glycosylation / Hamsters / Health aspects / Humanities and Social Sciences / Humoral immunity / Immune response / Immune response (cell-mediated) / Immune system / Immunity / Immunogenicity / Infections / Lung diseases / Lungs / Macaca fascicularis - genetics / Macaca fascicularis - immunology / Macaca fascicularis - virology / Male / Mesocricetus - genetics / Mesocricetus - immunology / Mesocricetus - virology / Mice / multidisciplinary / Pandemics / Respiratory diseases / Safety / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - chemistry / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - immunology / Spike Glycoprotein, Coronavirus - metabolism / Vaccines / Vaccines, Attenuated - administration & dosage / Vaccines, Attenuated - adverse effects / Vaccines, Attenuated - genetics / Vaccines, Attenuated - immunology / Vector-borne diseases / Viral antibodies / Viral diseases / Viral infections / Viruses / Yellow Fever Vaccine - genetics