A new vaccine can reproduce independently in the body. The vaccine called ARCT-154 has just received permanent approval as the first of its kind. At first glance, the new vaccine, like the Covid vaccine from Biontech and Moderna, consists of mRNA – the biomolecule provides the building instructions for the spike protein that is on the surface of the Sars-CoV-2 coronavirus. As soon as the vaccines enter a person’s body cells, they begin to produce the spike protein according to the instructions from the mRNA; the immune system is warned and forms antibodies against the foreigner.
But while the conventional vaccines only contribute briefly to the production of the corona spike in the cell and are soon broken down, the new vaccine multiplies in the body. According to proponents of this technology, which is called “self-amplifying mRNA” (sa-mRNA), this has some advantages. Smaller amounts, which are only one sixth to one tenth as large as those of previous mRNA vaccines, may be sufficient to trigger a strong immune response. This also means that spike proteins are available in the body for a longer period of time, which in turn strengthens the immune response. The immunologist Drew Weissman, who has just received a Nobel Prize for his fundamental work on mRNA vaccination and advises the manufacturer Arcturus Therapeutics, is certainly hopeful about the self-replicating vaccines. He said he thinks it’s a very sustainable option according to a press release.
“An incredible endorsement for this field.”
The new vaccine has so far only been approved in Japan. The most important study to date on the benefits and risks of the product also took place there. According to the study, which has not yet been published in a specialist journal, the ARCT-154 vaccine has largely fulfilled the hopes placed on it: As part of the study, 828 test subjects who had already been vaccinated three times received a fourth vaccination – either with ARCT-154 or with the Biontech vaccine Comirnaty. Four weeks later, the antibody levels against the coronavirus had increased by a factor of 6.7 in those vaccinated with ARCT-154, but only by a factor of 4.4 in those vaccinated with Biontech. However, ARCT-154 did not prove to be milder: vaccination reactions occurred with similar frequency in both groups. 95 percent of those vaccinated with ARCT-154 and 97 percent of those vaccinated with Biontech reported local reactions at the injection site. Almost two thirds of those vaccinated in both groups complained of malaise and other symptoms such as headaches, chills or muscle pain.
This could be because the optimal dose has not yet been found, said vaccine researcher Niek Sanders from the University of Ghent, Belgium the magazine Nature. With sa-mRNA vaccines, it is sometimes tricky to find the right amount of mRNA and the right additional genes so that the desire for optimal effect with minimal side effects is fulfilled.
The new vaccine can replicate itself because it not only contains the mRNA for the spike protein, but also genes for the enzyme replicase, which replicates the mRNA. The biochemical machines that the vaccine needs come from the Venezuelan equine encephalitis virus. This pathogen can cause brain inflammation in horses and humans, but the vaccine only contains individual genes from this virus, so it cannot cause the disease.
Research into sa-mRNA has been going on for around 20 years, and there are also several companies and start-ups that have specialized in this topic. The first approved vaccine is “an incredible validation for this field,” said Nathaniel Wang, co-founder of Replicate Bioscience in San Diego, which is also developing sa-mRNA vaccines. Twelve sa-mRNA vaccine candidates are currently in clinical trials internationally. Some are directed against infectious diseases such as influenza or shingles, others are intended to help with cancer. But there are also other possible applications, for example the production of healing proteins in the body using the injected sa-mRNA.