Sanofi’s mRNA COVID-19 Vaccine Elicits High Antibody Levels

Sanofi and Translate Bio recently announced positive preclinical results for their mRNA-based COVID-19 vaccine candidate in mice.

Specifically, the candidate called MRT5500 induced "potent" neutralizing antibodies against COVID-19, with levels significantly higher than those previously observed in infected patients. 

Just after one administration, all dose levels saw a 100 percent increase in serum antibody concentration (seroconversion). Additionally, antibody titers were observed across all dose levels after receiving the two-dose-administration regimen. 

But in the higher dose groups (5 micrograms, 10 micrograms), titers were detected after one administration of MRT5500 and were more notable after the second administration.

“Today’s presentation of these positive results is another development milestone for providing a safe and effective potential vaccine against SARS-CoV2 and shows how promising this technology is,” Thomas Triomphe, executive vice president and global head of Sanofi, said in the announcement. 

In mice, researchers assessed four dose levels of the mRNA-based vaccine, at 0.2, 1, 5, and 10 µg per dose using a two-dose vaccination schedule administered three weeks apart. 

But in non-human primates, three dose levels were assessed at 15, 45, and 135 micrograms per dose. Researchers then evaluated the potency of the mRNA-based vaccine candidate by two types of neutralizing assays: pseudovirus neutralization and micro-neutralization. 

A pseudovirus neutralizing assay is a retrovirus that can “integrate the envelope glycoprotein of another virus to form a virus with an exogenous viral envelope.” But the genome receives the characteristics of the retrovirus itself. 

And micro-neutralization assay measures what individuals are infected with influenza virus and if virus replication occurred. 

After the first administration of MRT5500, most non-human primates developed neutralizing antibodies against the COVID-19 spike protein significantly higher than those from human convalescent sera by Day 35, researchers noted.

It was also demonstrated that MRT5500-immunized mice and non-human primates exhibited a Th1-biased T cell response against SARS-CoV-2.

“The preclinical results we report in this paper demonstrate the ability of MRT5500 to elicit a favorable immune response in both mice and non-human primates. Importantly, these results provide additional support for using our mRNA platform to potentially expedite the development of alternative approaches to traditional vaccines,” said Ronald Renaud, chief executive officer at Translate Bio. 

A Phase 1/2 clinical trial of the mRNA-vaccine candidate is anticipated to begin in the fourth quarter of 2020.

mRNA-based vaccines are an alternative to standard vaccine approaches because they have high potency, ability to initiate protein production, and present an option for a rapid and safe treatment at a low-cost.

Many top pharmaceutical companies, such as Moderna,  Pfizer, and BioNTech have also released positive results for their mRNA-based COVID-19 vaccine candidates. 

Additionally, in July, NIH and Moderna launched a Phase 3 clinical trial for their mRNA-based vaccine candidate just a month after the Phase 2 study commenced. 

The trial enrolled 30,000 patients to uncover if mRNA-1273 could prevent symptomatic COVID-19 after two doses. The trial also aims to study whether the candidate can prevent severe COVID-19 in patients with or without disease symptoms.

Results from the trial are expected in the fourth quarter of 2020. 

At the end of August, Pfizer and BioNTech also shared that their mRNA COVID-19 vaccine candidate, BNT162b2, which elicited SARS-CoV-2 neutralizing geometric mean titers (GMTs) in younger adults just seven days after a second 30 microgram dose of the candidate.

Specifically, patients showed GMTs that were 3.8 times the GTM of 38 sera of SARS-CoV-2 convalescent patients and 1.6 times the GMT of the same panel seven days after a second 30 microgram dose. 

Notably, less than 20 percent of the participants suffered from a mild to moderate fever reaction.