Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains

• Published in: bioRxiv
• Main Authors: Stewart-Jones, Guillaume, Elbashir, Sayda M, Wu, Kai, Lee, Diana, Renzi, Isabella, Baoling Ying, Koch, Matthew, Sein, Caralyn E, Choi, Angela, Whitener, Bradley, Garcia-Dominguez, Dario, Henry, Carole, Woods, Angela, Ma, Lingzhi, Daniela Montes Berrueta, Avena, Laura E, Quinones, Julian, Falcone, Samantha, Hsiao, Chiaowen J, Scheaffer, Suzanne M, Thackray, Larissa B, White, Phil, Diamond, Michael S, Edwards, Darin K, Carfi, Andrea
• Format: Paper Journal Article
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 07.10.2022; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Biotechnology; Coronaviruses; COVID-19; Immune response; Immunology; mRNA; mRNA vaccines; Severe acute respiratory syndrome coronavirus 2; Spike protein; COVID-19; mRNA-1283; RBD; vaccines; challenge; mice; immunogenicity; viral variants; NTD
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2022.10.07.511319

With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 (NCT05137236). Competing Interest Statement Guillaume B.E. Stewart-Jones, Sayda M. Elbashir, Kai Wu, Diana Lee, Isabella Renzi, Matthew Koch, Caralyn E. Sein, Angela Choi, Dario Garcia-Dominguez, Carole Henry, Angela Woods, LingZhi Ma, Daniela Montes Berrueta, Laura E. Avena, Julian Quinones, Samantha Falcone, Chiaowen J. Hsiao, Phil White, Darin K. Edwards, Andrea Carfi are consultant or employees of and shareholders in Moderna Inc. Michael S. Diamond is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Moderna, inc., and Immunome. Bradley Whitener, Baoling Ying, Suzanne M. Scheaffer, Larissa B. Thackray, and Michael S. Diamond received unrelated funding support in sponsored research agreements from Vir Biotechnology, Immunome, Emergent BioSolutions, and Moderna, Inc.