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1.
iScience ; 25(8): 104705, 2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-1914523

ABSTRACT

Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent patient with COVID-19, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 D614G, beta, gamma, and delta infection in vitro, with three mAbs neutralizing omicron as well. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta, and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 µg/mL, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.

2.
Nature ; 590(7845): 320-325, 2021 02.
Article in English | MEDLINE | ID: covidwho-953381

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.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Genetic Vectors/genetics , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Yellow Fever Vaccine/genetics , Animals , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/genetics , Cricetinae , Disease Models, Animal , Female , Glycosylation , Macaca fascicularis/genetics , Macaca fascicularis/immunology , Macaca fascicularis/virology , Male , Mesocricetus/genetics , Mesocricetus/immunology , Mesocricetus/virology , Mice , Safety , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/genetics
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