The European Medicines Agency (EMA) has approved Kostaive (ARCT-154), a new Self-Amplifying Vaccine, a mRNA (sa-mRNA) COVID-19 vaccine developed by CSL and Arcturus Therapeutics, for use in individuals aged 18 and older, and it is now being rolled out in the European Union (EU). This development is seen as an important step in the effort to produce vaccines much more quickly than before to handle new virus outbreaks, a goal driven by the EU which is also investing in the further development of the RNA vaccines. While Kostaive is claimed to represents a significant advancement in vaccine technology due to its expected ability to amplify mRNA within cells, something said to reduce the required vaccine dose and meant to enhance immune responses, critiques and concerns have been raised by scientists and observers, particularly regarding safety, long-term effects, and ethical considerations.
Critics are voicing severe safety concerns pointing to the very imited long-term research done and the very high rates of serious side effects among clinical trial participants for Kostaive; 90% adverse event rate, 5 deaths. Although the EMA states that most side effects are mild and comparable to those of conventional mRNA vaccines (pain at the injection site, fatigue, headache), the lack of detailed, publicly available data on severe adverse events has raised concerns. For instance, a Phase III trial reported one hepatic event potentially linked to the vaccine, which critics argue warrants further scrutiny as the vaccine is rolled out to larger populations. Comparing Kostaive with mRNA vaccines is also a bit of an issue as they have already shown to cause an uncomparably gigantic amount of recorded reports of damages.
Self-amplifying mRNA vaccines are a novel technology, and Kostaive is the first sa-mRNA vaccine approved by the EMA, but already 33 other candidates are under development. The sa-mRNA vaccine distinguishes itself by being a self-amplifying vaccine that replicates in the body, the injection containing a self-amplifying messenger RNA molecule (sa-mRNA or saRNA) called zapomeran. This molecule carries instructions to produce a protein, in the case of Kostaive, from the original strain of SARS-CoV-2, the virus that is said to cause Covid-19. In addition to this, the vaccine also contains instructions to produce an enzyme that creates further copies of mRNA inside the cells. This mechanism means that the body itself functions as a copying machine for RNA, resulting in a higher and more long-lasting production of antigen. The salepitch is that this will enable the use of lower vaccine doses to achieve a similar immunological effect as previous mRNA vaccines. Unpredictable accumulations of the spike protein have also been a problem with the previous mRNA technology. The clinical relevance of higher antibody levels in Kostaive is unclear, as no large-scale efficacy studies have directly correlated these immunological outcomes with reduced disease severity or transmission.
That Kostaive targets the spike protein of the original SARS-CoV-2 strain, which limits its effectiveness against newer variants as these consistently evolve rapidly and the focus on the original strain reduces any potential positive impact on public health, something also not discussed.
The prolonged mRNA and protein production makes the vaccine behave like a syntethic virus several critics say. Its potential for unintended consequences such as prolonged inflammation and the biodistribution of lipid nanoparticles (LNPs) used to deliver the sa-mRNA distribute to non-target tissues, causing off-target effects is very concerning as is the high risk of auto-immune responses, excessive immune responses, triggered by the prolonged antigen production, yet no long-term safety profile is established due to the short duration of clinical trials. Swissmedic, a regulatory authority, has reportedly requested additional information on LNPs, biodistribution, and risks of autoimmunity, suggesting these are areas of ongoing issues.
Jonathan Gilthorpe, Senior Lecturer at the Department of Medical and Translational Biology at Umeå University, says in an interview to Swedish Epoch Times that the vaccine is a genetic engineering and the effects of the new technology (saRNA) is likely to have huge ramifications. He emphasizes that it is still unclear where in the body the spike protein will be formed, how long it will remain, and how it will affect different individuals, as reactions to this type of injection vary a lot.
The potential for sa-mRNA vaccines to cross the placental barrier due to the use of LNPs is another concern. This is particularly worrisome for individuals who may become pregnant, as the effects of sa-mRNA vaccines on fetal development are not studied. The EMA has noted that Kostaive has not been studied in pregnant individuals, the lack of data in this population is a significant gap.
Kostaive is not the only replicate type of vaccine already out on the market. Merck has injections available for dogs and cats. Nicholas Hulscher, an epidemiologist, writes on his substack: “Meanwhile, the USDA quietly approved an experimental self-amplifying RNA injection for dogs developed by Merck in June 2024: Nobivac NXT Canine Flu H3N2. It appears that Merck is attempting to camouflage the fact that this product is self-amplifying. The primary product description only indicates that it uses “revolutionary RNA particle technology.” However, the novel platform works by RNA particles targeting dendritic cells, where they self-replicate and result in sustained antigen production.” There is also one for cats, Nobivac NXT FeLV, marketed as “ground-breaking” and “uncompromising safety and efficiancy”, despite the very limited testing published.
Shedding
Nicholas Hulscher notes that none of the clinical trials for sa-mRNA vaccines have adequately addressed the potential for “product shedding.” Shedding refers to the risk that vaccinated individuals release vaccine components (e.g., mRNA or spike protein) into the environment, affecting others. While there is no definitive evidence of shedding with sa-mRNA vaccines, the lack of studies investigating this issue is alarming.
The everpresent risk of shedding also have huge ethical concerns. The potential violation of bodily autonomy for unvaccinated individuals as they could be exposed to vaccine components such as mRNA, lipid nanoparticles, or spike proteins without their consent is an issue but the right of individuals to make their own medical decisions without unintended influence from others has repeatedly been proven of no interest to neither politicians, governements, health agencies nor vaccine manufacturers. Vaccinated individuals could mean unquantified risks for others.
Vaccinated individuals have not been adequately informed about their potential to transmit vaccine components to others. Ethical informed consent necessitates that patients understand all relevant risks, including those that might affect others. The failure to communicate this possibility, or the absence of data definitively ruling it out, erodes the little trust left in healthcare providers and regulatory bodies.
The risk of shedding also brings to the forefront concerns about potential harm to vulnerable populations. Groups such as immunocompromised individuals, pregnant women, and children, who may not be eligible for vaccination or might face higher risks from exposure, could be particularly susceptible. The absence of data on shedding’s effects on these groups raises ethical concerns about non-maleficence, the duty to do no harm. Specifically, concerns have been raised as mRNA lipid nanoparticles have been shown to cross the placental barrier. If shedding occurs, pregnant women exposed to vaccine components could face unknown risks to fetal health, amplifying ethical concerns about protecting future generations.
The ethical concerns surrounding shedding are heightened by the novel mechanism of sa-mRNA vaccines, with its amplifying of mRNA within cells, leading to prolonged antigen production. The absence of evidence disproving shedding, particularly for these novel vaccines, remains a critical gap that undermines informed consent, public trust, and the application of the precautionary principle.
Central approval for use in EU
Vaccines are approved centrally within the EU, which is also the case with Kostaive. The approval, Epoch Times writes, has taken place via the central procedure, where the EU Commission made a decision on approval based on a recommendation from the European Medicines Agency’s (EMA) scientific committee (CHMP). Through this approval, Kostaive becomes approved in all EU countries..
The development of the new vaccine is part of a larger goal to be able to produce vaccines against new viruses within 100 days. This idea comes from the Norwegian organization Coalition for Epidemic Preparedness Innovations (Cepi), which was founded in 2016 with support from several governments, foundations, and forums with the aim of preventing epidemics through the rapid development and distribution of vaccines. The EU has largely adopted Cepi’s goals and integrated parts of these ideas into its pandemic preparedness. The collaboration between Cepi and the EU has resulted in the funding of various vaccine programs, where Cepi has, among other things, received 100 million euros to support the development of Covid-19 vaccines. The EU also participates in global initiatives such as GloPID-R, where Cepi has an observer role.
The rapid development and accelerated approval of Kostaive, facilitated by the claim of an urgent need to address COVID-19, have led to regulatory processes having been rushed. EMA’s approval, based on clinical data from Phase 1/2/3 studies and booster trials, have not included sufficient scrutiny of long-term outcomes or adverse events. The fast tracked approal of these experiemental products are a violation of the precautionary principle as well as of bioethical principles. EMA and vaccine developers have not done anything to address these concerns and downplaying them without evidence is not a solution. The burden of proof lies solely with manufacturers and regulators.
