Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates

Abstract

An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority. 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.

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“…In Balb/c mice, two doses in the range of 0.2–10 µg resulted in binding and neutralization titers well above convalescent levels. In non-human primates 15, 45 and 135 µg doses all generated titers exceeding the human convalescent panel [ 56 ]. The immune response was also Th1 biased.…”

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“…Technically, this is the easiest vaccine production strategy. MRT5500 [ 167 ] is an mRNA vaccine produced by Sanofi and Translate Bio. Recently, the US pharmaceutical company Pfizer and the German pharmaceutical company BioNTech announced their initial research data on mRNA-based vaccine candidate BNT162b2 [ 168 ], claiming that the vaccine jointly developed by the two companies is as efficient as 90%, which is much higher than the minimum requirement of the FDA (50%).…”

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“…ARCoV is currently being evaluated in phase 1 clinical trials. Other mRNA vaccine candidates showed immunogenicity by eliciting potent neutralizing antibodies in mice and/or NHPs ( 121 , 122 ).…”