PT  - JOURNAL ARTICLE
AU  - Kirill V. Kalnin
AU  - Timothy Plitnik
AU  - Michael Kishko
AU  - Jinrong Zhang
AU  - Donghui Zhang
AU  - Adrien Beauvais
AU  - Natalie G. Anosova
AU  - Timothy Tibbitts
AU  - Joshua M. DiNapoli
AU  - Po-Wei D. Huang
AU  - James Huleatt
AU  - Deanne Vincent
AU  - Katherine Fries
AU  - Shrirang Karve
AU  - Rebecca Goldman
AU  - Hardip Gopani
AU  - Anusha Dias
AU  - Khang Tran
AU  - Minnie Zacharia
AU  - Xiaobo Gu
AU  - Lianne Boeglin
AU  - Sudha Chivukula
AU  - Ron Swearingen
AU  - Victoria Landolfi
AU  - Tong-Ming Fu
AU  - Frank DeRosa
AU  - Danilo Casimiro
TI  - Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
AID  - 10.1101/2020.10.14.337535
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.14.337535
4099  - http://biorxiv.org/content/early/2020/10/14/2020.10.14.337535.short
4100  - http://biorxiv.org/content/early/2020/10/14/2020.10.14.337535.full
AB  - An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority1. Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.Competing Interest StatementThe authors have declared no competing interest.