At the end of February 2020, the Modern Pharmaceutical Company (MRNA), located near Boston, announced that its prototype vaccine against the new coronavirus was ready to move to phase 1 of the trials and begin testing in humans. Now, the company has just published a note in which it advances the preliminary results of these first trials, led by the National Institute of Allergies and Infectious Diseases of the United States. Although it is a very small sample and the data will have to be confirmed in successive phases, these look promising : the vaccine could be safe and capable of eliciting a strong immune response in the participants.
RNA-based vaccine
The vaccine against SARS-CoV-2 consists of inoculating genetic instructions, in this case RNA, that will be able to induce in human cells the formation of a coronavirus protein, which is what can provoke the immune response. Specifically, the production of protein S, essential for host cell attachment and infection, is stimulated. In this way, it is possible to reproduce the orders given by SARS-CoV-2 when it infects a cell without needing to inoculate the complete virus. Antibodies capable of neutralizing this protein will therefore block the infectivity of the virus.
Phase 1 trials
In this first stage of the human clinical trials, 45 volunteers between 18 and 55 years of age participated, divided into three groups. One of the objectives of phase 1 is to verify which dose of the vaccine is safe, and therefore each group has received two doses of it at different levels: 25 micrograms (µg), 100 µg and 250 µg. Preliminary results are already available for the first two, as well as for the first 250 µg dose.
Two weeks after receiving the first dose, all the participants developed antibodies to SARS-CoV-2, and the higher the dose of vaccine, the greater the immune response. All the results for this first trial are not yet known, as the lowest doses were started first and, noting that there were no serious side effects, the trials were started with the higher doses. Moderna also has not provided data on the amount of antibodies produced at each dose or on whether there have been significant differences in the immune response between the participants.
In other parallel studies carried out in mice, in addition, it has been shown that the vaccine prevents the replication of the virus in lung cells.
Safety
The vaccine would present a safety profile consistent with that observed in previous clinical trials for other vaccines against infectious diseases developed by Moderna. In the 25 µg and 100 µg dose groups, only one adverse effect classified as grade 3 was experienced in one participant who received 100 µg and exhibited transient redness around the injection site. In the 250 µg group, three patients with grade 3 systemic symptoms were observed after the second dose. All adverse events were transient, self-resolving, and no higher grade adverse events have been reported.
Based on these results, in phase 2 two dose levels will be studied in depth: 50 µg and 100 µg. In addition, the phase 1 study is being modified to include a 50 µ dose level cohort.
What dates are being considered?
The team of researchers has just received approval from the US Food and Drug Administration (FDA) to conduct phase 2 trials, which are expected to begin in a few days. In addition, the company is currently finalizing the protocol for phase 3, which would begin in July.
“These provisional data, albeit early, show that the experimental vaccine elicits an immune response of the same magnitude as that caused by a natural infection, and that this response occurs even at a dose as low as 25 µg,” explained Tal Zaks, medical director in the company. “When combined with the success in preventing viral replication in the lungs of a preclinical model at a dose that elicited similar levels of neutralizing antibodies, the data supports our belief that this vaccine has the potential to prevent COVID disease. -19 “.
If successful, the company expects to have the vaccine ready for distribution in the US by the end of the year, and in early 2021 it could be available to other countries.
Can we sing victory? Let’s wait until phase 3
As we have already commented, the results advanced by Moderna in its press release are preliminary, they belong to a very small sample and, this is very important, the participants belong to the youngest age group.
“Until the phase 3 trial is completed, it will not be known if the vaccine is really effective in preventing COVID-19 disease,” Stephen Evans, professor of pharmacoepidemiology at the School of Hygiene and Tropical Medicine , explained to the Science Media Center. from London, and who has not participated in the study. “ The goal of phase 1 is not to demonstrate efficacy in reducing or preventing disease , but to measure what is called ‘immunogenicity’, which is the antibody response, a minimum requirement for the vaccine to work. On the other hand, ‘reactogenicity’ is also evaluated, which studies whether there are immediate reactions to the vaccine ”, explains the expert.
The whole world is waiting with anticipation for the arrival of the long-awaited vaccine and, although the results are encouraging, experts recommend caution: until the results of phase 3 arrive, we will not really know the vaccine is really effective to protect ourselves against COVID-19 .
