In late February 2020, the modern pharmaceutical company (MRNA), located near Boston, announced that its prototype vaccine against the new coronavirus was ready to go to phase 1 of the trials and begin testing in humans. Now, the company has just published a note that advances the preliminary results of these first trials, led by the US National Institute of Allergy and Infectious Diseases. Although this is a very small sample and the data will have to be confirmed in the subsequent phases, these seem promising: the vaccine could be safe and capable of generating a powerful immune response in the participants.
RNA-based vaccine
The SARS-CoV-2 vaccine consists of inoculating genetic instructions, in this case RNA, that will be able to induce the formation of a coronavirus protein in human cells, which is what can provoke the immune response. Specifically, the production of protein S is stimulated, essential for the binding and infection of the host cell. 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 entire virus. The antibodies able to neutralize this protein, therefore, block the infectivity of the virus.
Phase 1 trials
In this first stage of human clinical trials, 45 volunteers between 18 and 55 years old participated, divided into three groups. One of the objectives of phase 1 is to check which dose of the vaccine is safe, and therefore each group has received two doses of the vaccine at different levels: 25 micrograms (µg), 100 µg and 250 µg. The preliminary results are already available for the first two, as well as for the first dose of 250 µg.
Two weeks after receiving the first dose, all participants developed antibodies to SARS-CoV-2, and the higher the vaccine dose, the greater the immune response. Not all of the results for this first trial are known yet, as we first started with the lowest doses, and seeing that there were no serious side effects, we started the trials with the higher doses. Moderna has also 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 in mice, the vaccine has also been shown to prevent replication of the virus in lung cells.
Security
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 a grade 3 adverse effect was experienced in a participant who received 100 µg and had transient redness around the injection site. In the 250 µg group, three patients with systemic grade 3 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, 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 carry out the phase 2 trials, which are expected to start in a few days. In addition, the company is currently finalizing the protocol for phase 3, which would start in July.
“These provisional data, although early, show that the experimental vaccine elicits an immune response of the same magnitude as that caused by natural infection, and that this response occurs even at a dose as low as 25 µg, Tal Zaks explained, medical director at the company. “When combined with the success in preventing viral replication in the lungs from a preclinical model at a dose that caused similar levels of neutralizing antibodies, the data corroborate our belief that this vaccine has the potential to prevent COVID disease. -19 “.
If successful, the company hopes 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 younger 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, told 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 looking forward to 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 that the vaccine is really effective in protecting us against COVID-19.