The United States’ health authorities will soon request that millions of Americans receive booster vaccines against COVID-19. Vaccines are created by drug companies, but must be approved by regulators to be safe and effective for human consumption. In stunning newsMany health experts were baffled when the U.S. Food and Drug Administration indicated that they would accept efficacy data from animals using the most recent COVID-19 subvariants Omicron Ba.4 and Omicron Ba.5, which left many others scratching their heads. in lieuHuman data. These results will be combined with safety data from an earlier Omicron Subvariant, BA.
This unprecedented move by the FDA is likely to be driven by the desire to speed up regulatory approval in time for a Fall 2022 boost rollout. On August 17, White House COVID-19 Response Coordinator Ashish Jha asserted that boosters will be available to teens and adults “in a few short weeks.” On August 31, the FDA approved the COVID-19 boostersIn a rush, you may not be able to complete the final authorization process by the Centers for Disease Control and Prevention. However, substituting critical health data in humans for animal results is a dangerous practice.
Vaccines are amongst the most reliable public interventions against infectious diseases. Vaccinations have been used to immunize people for years. crucial in protecting human health. One good example of the benefits of vaccines is the dramatic difference in the number COVID-19 deaths between 2005 and 2009. unvaccinated and vaccinated individuals. Vaccines do not provide protection against all diseases. For instance, new variants can go undetected by the immune system and “outsmart” the immunity offered by earlier immunization. As you can see, the immune system weakens as we age and when other medical conditions are present. in COVID-19 patients.
By design, COVID-19 boosters seek to enhance one’s protection from coronavirus and confer immunity against new emerging variants. Coronaviruses and other viruses change constantly. faster than a vaccine can stop them. More than 12 variants of COVID-19To date, no other known cases have been reported. Omicron is one of the most important and controversial vaccines in the world. Omicron also has many subvariants, such as the Omicron BA.1, Omicron.4 and Omicron.5.
During the COVID-19 pandemic, health officials often used the term “flattening the curve” as a key public health strategy. The curve is a visual representation that shows the number of patients who need care over time. The curve can be kept flat by effective immunization boosters, which are available in COVID-19 variants or subvariants. This will reduce the pressure on health care systems, allow for better vaccine development, and prevent another pandemic.
The U.K. approved a dual COVID-19 vaccine on August 15. It targeted Omicron BA.1 as well as the original virus, SARS.CoV-2. This approval was based in part on solid safety and efficacy information gathered from a clinical trial investigating Omicron BA.1. BA.5 is currently the most popular Omicron subvariant, accounting for a whopping 80% of all Omicron subvariants in the U.S. almost 90 percent of new COVID-19 infections,According to the CDC. It is also thought to be the most contagious.
U.S. regulators opted for this option. not to adopt the strategyTheir counterparts in the U.K. Instead, the FDA asked drug companies to develop multivariant booster shots in June 2022. This would allow them to protect against multiple variants simultaneously, including the most recent BA.4 or BA.5 subvariants. Drug makers are often in a race against their time to create vaccines for the latest variants and get regulatory approval. This involves the generation of preclinical data usually in artificial animal models. Then, clinical trials are used to determine safety and efficacy in humans. These trials are also known as first-in-human (FIH) trials. This type of trial is still required for approval of pharmaceutical drugs and vaccines.
There are many issues at play here. First, subvariants like BA.1, BA.4 & BA.5 have different acute effects than the original virus. They can cause havoc on the immune system as well as their ability to evolve and spread. Nearly all of the new COVID-19 variants, even the Omicron subvariants have not been fully characterized. We don’t know enough about the subvariants to be able to test them in humans before making booster vaccines available for millions. We are only beginning to understand their long-term effects.
Second, substituting efficacy data in mice or artificial animal models for human data is a remarkable thing under any circumstances. It is not surprising that many scientific discoveries in animals do not translate into medical discoveries in humans. 90 percent of experimental drugs that were tested on animals fail to work in humans because of safety or efficacy concerns. Animal data used in clinical applications should be treated with the greatest skepticism in most cases.
Separately, it is hard to reconcile this FDA approach with the landmark decision taken at the March 2020 meeting of the International Coalition of Medicines Regulatory Authorities (ICMRA) — more specifically during the Global regulatory workshop on COVID-19 vaccine development. There, global regulators stipulated that, “It is not required to demonstrate the efficacy of the SARS-CoV-2 vaccine candidate in animal challenge models prior to proceeding to FIH clinical trials.” That important policy decision was a vital step to accelerate the development of successful vaccines in the first place. The FDA is now promoting the opposite.
Retrospectively, much of COVID-19’s animal data generated during pandemic caused more questions than answers. Had it not been for the world’s full attention on developing vaccines, relying only on artificial animal models for directions and “next steps” could have been catastrophic from the standpoint of saving time or generating actionable information. Studying COVID-19 in mice is misleading, for instance. This is the most widely used model in the world. Mice — unlike humans — are not naturally susceptible to COVID-19 due to a key structural difference between the two species in their host-pathogen interaction. For example, ACE2, a cell surface receptor that allows coronaviruses infect cells, is unresponsive in mice. Murine models had to be artificially modified or “humanized” before they could be infected.
Non-human primates (NHPs), which are closer to humans than any other species, also showed very impressive results. mild clinical symptomsSARS-CoV-2 rendered them virtually unreliable as research models. SARS-CoV-2-infected NHPs did not suffer from any deaths due to disease burden. This makes them ineligible for modeling COVID-19-induced multisystem organ dysfunction, which is a hallmark of COVID-19 related deaths. A thorough examination of the many reveals that they are actually quite objective. artificial animal models used to study COVID-19 reveals disparate characteristics — with hardly any capturing the sequela of COVID-19 infections in humans. These discrepancies are due to radical structural, physiological, metabolic, and behavioral differences among species.
To be fair, the FDA has taken concrete measures to explore new technologies that could reduce dependence on artificial animal models. These include advancing the science and applications of Microphysiological Systems (MPS) — a category of sophisticated research tools, like Organ-Chips, also known as alternative methods to animal experimentation. These advanced systems are possible because of the convergence of many disciplines, such as biophysics and regenerative medicine. The FDA was, for example, a co-host at the inaugural World Summit focusing on MPS2022 and earlier in 2022. The agency also supports programs like the Predictive Toxicology Roadmap ISTANDSimilar goals. More recently, a new initiative, although poorly funded, has been conceived by the FDA “to implement a cross-agency New Alternative Methods Program.” In its budget proposal for fiscal year 2023, the agency expressly stated that, “New alternative methods have the potential to provide both more timely and more predictive information to accelerate product development and enhance emergency preparedness.” In addition to Organ-ChipsAlternate methods include artificial Intelligence (AI) or machine-learning approaches, as well three-dimensional (3D), Bioprinting Techniques, which are advanced engineering techniques for the fabrication and modification of biomedical components that replicate the features found in natural human tissues.
All of this takes place in a climate where legislative momentum is building to advance research methods that are based upon human biology (e.g. the FDA Modernization Act). At top biotech companies and academic institutions, efforts to achieve similar goals are underway. The decision to rely on animal efficacy data for regulatory approval of booster vaccines is not in line with growing human relevance. It could also reflect competing dogmas within agency regarding regulatory approvals of booster vaccines.
The FDA’s seemingly mixed-and-matched approach to vaccine efficacy, whereby critical data in humans is substituted for efficacy data in other animals, and safety data on Omicron subvariants, sets a negative precedent. This could backfire. While COVID-19 vaccination is vital for public health, relying on animal data is a dangerous gamble. This is a dangerous reliance that can lead to cutting corners and not a smart health policy. To make matters worse, vaccination detractors will use any reports of health complications or deaths that could be avoided with human data to increase skepticism and undermine a public health program. The FDA should explore other scenarios, such as obtaining data from representative human cohorts, or allowing for clinical trials results on Omicron Subvariants to be completed, in order to support the Fall 2022 boosters. The agency must continue to support MPS technologies and similar human-based methods as viable alternatives to animal experimentation in the long-term. The FDA will not be looking ahead if this is not achieved.