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Authors:Ugur Sahin1,2, Alexander Muik1Evelyna Derhovanessian1, Isabel Vogler1, Lena M. Kranz1, Mathias 5  Vormehr1, Alina Baum4, Kristen Pascal4, Jasmin Quandt1, Daniel Maurus1, Sebastian Brachtendorf1, 6  Verena Lörks1, Julian Sikorski1, Rolf Hilker1, Dirk Becker1, Ann-Kathrin Eller1, Jan Grützner1, Carsten 7  Boesler1, Corinna Rosenbaum1, Marie-Cristine Kühnle1, Ulrich Luxemburger1, Alexandra Kemmer- 8  Brück1, David Langer1, Martin Bexon7, Stefanie Bolte1, Katalin Karikó1, Tania Palanche1, Boris 9  Fischer1, Armin Schultz6, Pei-Yong Shi5, Camila Fontes-Garfias5, John L. Perez3Kena A. Swanson3, Jakob Loschko3, Ingrid L. Scully3, Mark Cutler3, Warren Kalina3, Christos A. Kyratsous4, David Cooper3, Philip R. Dormitzer3, Kathrin U. Jansen3Özlem Türeci 

Journal/ Pre-Print:bioRxiv      

Tags: Immunology/Immunity, Therapeutics , Vaccines, Virology  

Research Highlights 

1.Two injectionofa potential COVID-19 RNA vaccine at 4 dose levels (1ug, 10, ug, 30 ug, 50 ug), encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein leads to development of IgG antibodies, serological neutralising titers and T-cell immune responses. The 60 ug dose-level cohort received only a priming dose 

2. Participants immunological responses were evaluated at day 7th and 21st after baseline priming and boosting dose in 12 participants of each group. RBD-binding IgG antibodies increased 21 days after priming dose, which further increased after boosting 

3.RBD-binding IgG concentrations were above those in a COVID-19 convalescent human serum panel. 

Summary 

In this phase 1/2 open-label dose-ranging clinical trialantibodies and T-cell responses were evaluated for a potential COVID-19 RNA vaccine. In contrast to the dose-dependency of RBD-binding IgG and neutralisation antibodies, there was no clear dose-dependency of T-cell responses. RBD-specific CD4+ and CD8+ T-cells secreted IFN-g and IL-2, with a very broad response among the vaccinees. CD4+ T-cells didn’t express IL-4. Supernatants of PBMCs showed pro-inflammatory cytokines (TNF, IL-1B, IL-12p70) but not IL-4 nor IL-5. 

Impact for SARS-CoV2/COVID19 research efforts 

  • Develop a vaccine for SARS-CoV2/COVID19 

Study Type 

  • In vivo study (Phase 1/2, open-label dose-ranging clinical trial with 12 participants each group in Germany)

Strengths and limitations of the paper 

Novelty: First-in-human clinical trial evaluating immunological responses of RBD COVID-19 RNA vaccine                  

Standing in the field: see. Translatability          

Appropriate statistics: Yes 

Viral model usedClinical trial evaluating immunological responses of RBD COVID-19 RNA vaccine      

Translatability:  If the mentioned potential vaccine (BNT16261) is efficacious in further phases of the clinical trials, it can be administered to the population if it is also safe in vulnerable populations since the study didn’t recruit participants older than 55 years old nor participants at higher risk of being exposed to COVID-19 

Main limitations:  

  • Small sample size (12 participants each group) 

  • Two doses needed to achieve immunogenicity comparable to a single dose of an e.g. viral vectored vaccine 

  • Open-label study and not blinded, no randomisation 

  • No further T-cell analyses (TCR repertoire analysis) 

  • In the absence of correlates of protection against SARS-CoV-2, vaccine immunogenicity can not be interpreted for future efficacy.