Optimization of Non-Coding Regions for a Non-Modified mRNA COVID-19 Vaccine.
Makda S. Gebre,Susanne Rauch,Nicole Roth,Jingyou Yu,Abishek Chandrashekar,Noe B. Mercado,Xuan He,Jinyan Liu,Katherine McMahan,Amanda J. Martinot,David R. Martinez,Tori Giffin,David L. Hope,Shivani A. Patel,Daniel Sellers,Owen Sanborn,Julia Barrett,Xiaowen Liu,Andrew C. Cole,Laurent Pessaint,Daniel Valentin,Zack Flinchbaugh,Jake Yalley-Ogunro,Jeanne Muench,Renita Brown,Anthony L. Cook,Elyse Teow,Hanne Leth Andersen,Mark G. Lewis,Adrianus C. M. Boon,Ralph S. Baric,Stefan O. Mueller,Benjamin Petsch,Dan H. Barouch,Dan H. Barouch +34 more
TLDR
In this paper, a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates was conducted.Abstract:
The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine with non-modified nucleosides but optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including the delta variant. Moreover, CV2CoV proved comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tract. Binding and neutralizing antibody titers correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in nonhuman primates.read more
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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.
Journal ArticleDOI
COVID-19 mRNA vaccines: Platforms and current developments
TL;DR: A review of mRNA vaccines can be found in this paper , where a brief history and the current status of four mRNA vaccine platforms, nucleoside-modified and unmodified mRNA, circular RNA, and self-amplifying RNA, as well as an overview of the recent progress and status of COVID-19 mRNA vaccines are discussed.
Journal ArticleDOI
The landscape of mRNA nanomedicine
TL;DR: The recent success of the two highly efficacious mRNA vaccines produced by Moderna and Pfizer-BioNTech to protect against COVID-19 highlights the huge potential of mRNA technology for revolutionizing life science and medical research as mentioned in this paper .
Journal ArticleDOI
Unlocking the promise of mRNA therapeutics
TL;DR: Early clinical trials of mRNA therapeutics include studies of paracrine vascular endothelial growth factor (VEGF) mRNA for heart failure and of CRISPR-Cas9 mRNA for a congenital liver-specific storage disease as discussed by the authors .
Journal ArticleDOI
Innate immune mechanisms of mRNA vaccines
TL;DR: The lipid nanoparticle (LNP)-encapsulated, nucleoside-modified mRNA platform has been used to generate safe and effective vaccines in record time against COVID-19 as mentioned in this paper .
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