Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 : A phase 1 randomized clinical trial.
Peter G. Kremsner,P. Mann,Arne Kroidl,Isabel Leroux-Roels,Christoph Schindler,Julian J. Gabor,Mirjam Schunk,Geert Leroux-Roels,Jacobus J. Bosch,Rolf Fendel,Andrea Kreidenweiss,Thirumalaisamy P. Velavan,Mariola Fotin-Mleczek,Stefan O. Mueller,Gianluca Quintini,Oliver Schönborn‑Kellenberger,Dominik Vahrenhorst,Thomas Verstraeten,Margarida Alves de Mesquita,Lisa Walz,Olaf‑Oliver Wolz,Lidia Oostvogels +21 more
TLDR
In this article, the authors used the RNActive technology platform (CureVac N.V., Tubingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilised form of SARS-CoV-2 spike (S) protein encapsulated in lipid nanoparticles (LNP).Abstract:
We used the RNActive® technology platform (CureVac N.V., Tubingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tubingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.read more
Citations
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The tangled history of mRNA vaccines.
TL;DR: This paper showed that hundreds of scientists had worked on mRNA vaccines for decades before the coronavirus pandemic brought a breakthrough, and that these vaccines had been successfully used to prevent the pandemic.
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The clinical progress of mRNA vaccines and immunotherapies
TL;DR: The emergency use authorizations (EUAs) of two mRNA-based severe acute respiratory syndrome coronavirus (SARS-CoV)-2 vaccines approximately 11 months after publication of the viral sequence highlights the transformative potential of this nucleic acid technology as mentioned in this paper .
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Covid-19 vaccines and variants of concern: A review.
TL;DR: In this article, the most relevant mutations in the SARS-CoV-2 spike protein, discusses VE against VOCs, presents rare adverse events after Covid-19 vaccination and introduces some promising Covid19 vaccine candidates.
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Advances in COVID-19 mRNA vaccine development
Enyue Fang,Xiaohui Liu,Miao Li,Zelun Zhang,Lifang Song,Baiyu Zhu,Xiao-hong Wu,Jingjing Liu,Danhua Zhao,Yuhua Li +9 more
TL;DR: In this article , the authors summarized current knowledge on the structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials and real-world data of COVID-19 mRNA vaccines as well as mRNA technology.
Journal ArticleDOI
Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial
Peter G. Kremsner,Rodolfo Andrés Ahuad Guerrero,Eunate Arana-Arri,Gustavo Aroca Martínez,Marc J.M. Bonten,Reynaldo Chandler,Gonzalo Corral,Eddie Jan Louis De Block,Lucie Ecker,Julian J. Gabor,Carlos Alberto Garcia Lopez,Lucy Gonzales,María Angélica Granados González,Nestor Gorini,Martin P. Grobusch,Adrian D Hrabar,Helga Junker,Alan Kimura,Claudio F. Lanata,Claudio F. Lanata,Clara Lehmann,Isabel Leroux-Roels,Philipp Mann,Michel F. Martinez-Resendez,Theresa J. Ochoa,Theresa J. Ochoa,Theresa J. Ochoa,Carlos Alberto Poy,Maria Jose Reyes Fentanes,Luis Maria Rivera Mejia,Vida Veronica Ruiz Herrera,Xavier Sáez-Llorens,Oliver Schönborn-Kellenberger,Mirjam Schunk,Alexandra Sierra Garcia,Itziar Vergara,Thomas Verstraeten,Marisa Vico,Lidia Oostvogels,Luciano Lovesio,Fabián Diez,Franco Grazziani,Maria Cristina Ganaha,Viviana Judith Zalatnik,Ricardo Julio Dittrich,Lidia Espínola,Sandra Lambert,Andrea Longhi,Claudia Vecchio,María Mastruzzo,Alberto Moreno Fernandez,Silvina Borchowiek,Roberto Potito,Fernando Martin Guardiani,Sofia Castella,Monica Foccoli,Aldana Pedernera,Ariel Braida,Virginia Durigan,Carolina Martella,Antonela Bobat,Bruno Emilio Boggia,Sergio Andrés Nemi,Javier Gerardo Tartaglione,Fabián César Piedimonte,Jessie De Bie,Humberto Reynales Londoño,Paula Andrea Rodríguez Ordoñez,Johanna Marcela García Cruz,Leonardo Bautista Toloza,Margot Cecilia Ladino González,Adriana Pilar Zambrano Ochoa,Iñigo Prieto Pradera,Daniela Torres Hernandez,Diana Patricia Mazo Elorza,Maria Fernanda Collazos Lennis,Beatriz Vanegas Dominguez,Lina Marianur Solano Mosquera,Rolf Fendel,Wim Alexander Fleischmann,Erik Koehne,Andrea Kreidenweiss,Carsten Köhler,Meral Esen,Carola Horn,Sandra Eberts,Arne Kroidl,Kristina Huber,Verena Thiel,Sonia Mazara Rosario,Gilda Reyes,Laura Rivera,Yeycy Donastorg,Flavia Lantigua,Dania Torres Almanzar,Rosalba Candelario,Lourdes Peña Mendez,Nadia Rosario Gomez,Antonio Portolés-Pérez,Ana Ascaso del Río,Leonor Laredo Velasco,Maria Jesus Bustinduy Odriozola,Igor Larrea Arranz,Luis Ignacio Martínez Alcorta,María Isabel Durán Laviña,Natale Imaz-Ayo,Susana Meijide,Aitor García-de-Vicuña,Ana Santorcuato,Mikel Gallego,Gloria Mayela Aguirre-García,Jocelyn Olmos Vega,Pablo González Limón,Andrea Vázquez Villar,Jaime Chávez Barón,Felipe Arredondo Saldaña,Juan de Dios Luján Palacios,Laura Julia Camacho Choza,Eduardo Gabriel Vázquez Saldaña,Sandra Janeth Ortega Dominguez,Karen Sofia Vega Orozco,Ivonne Aimee Torres Quiroz,Alejandro Martinez Avendaño,Javier Herrera Sanchez,Esperanza Guzman,Laura Castro Castrezana,Guillermo Miguel Ruiz Palacios y Santos,Ronald Frank Jacobus de Winter,Hanna K de Jonge,Jenny L Schnyder,Wim Boersma,Lisa Hessels,Remco Djamin,Simone van der Sar,Rodrigo DeAntonio,Moisés Peña,Gabriel Rebollon,Marianela Rojas,Johnny Escobar,Bruno Hammerschlag Icaza,Digna Y Wong T,Paulo Barrera Perigault,Sergio Ruiz,Milagros Chan,Dommie Janneth Arias Hoo,Ana I Gil,Carlos R Celis,Maria Pia Balmaceda,Omar Flores,Mayra Ochoa,Bia Peña,Carolina de la Flor,Camille María Webb,Enrique Cornejo,Fatima Sanes,Valerie Mayorga,Gladys Valdiviezo,Suzanne Pamela Ramírez Lamas,Gustavo Alberto Grandez Castillo,Javier R. Lama,Milagros Erika Matta Aguirre,Lesly Angela Arancibia Luna,Óscar Carbajal Paulet,José Zambrano Ortiz,Anais Camara,Fernanda Guzman Quintanilla,Carmen Diaz-Parra,Jose Morales-Oliva,Rubelio E Cornejo,Sheby A Ricalde,Jhonny Vidal,Luis Rios Nogales,Darline Cheatham-Seitz,Giorgia Gregoraci,Alain Brecx,Lisa Walz,Dominik Vahrenhorst,Tobias Seibel,Gianluca Quintini +178 more
TL;DR: The HERALD trial as discussed by the authors is a randomized, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America.
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