FBR's COVID-19 ResourcesWe're committed to improving health through education
List of Resources
- The Centers for Disease Control and Prevention website
- White House briefings
- COVID-19 cases in the U.S.
- FEMA’s Rumor Control page
- American Anthropological Association’s webpage of COVID-19 resources
- SAGE Publishing’s COVID-19 webpage
- Research!America’s coronavirus resources
- Americans for Medical Progress’ COVID-19 resources
- American Society for Microbiology’s novel coronavirus (COVID-19) resources
- EARA’s global overview of how animals are helping in COVID-19 research
- BIO COVID-19 Therapeutic Development Tracker
Nearly every medicine, medical device, surgical procedure and therapy we have today has depended on animal testing and research. Animal research is one of the first steps in medical discovery.
“There are diseases in which you vaccinate someone, they get infected with what you are trying to protect them with, and you actually enhance the infection. You can get a good feel for that in animal models,” the director of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci, said during a White House briefing on March 26.
Contrary to the claims of animal rights groups, animal models have been and will continue to be crucial to medical development and public health.
The FBR team rounded up articles in the news in recent weeks on potential treatments and potential vaccines for the new coronavirus, as well as other COVID-19 developments, and the animal models used to develop them. In addition, Genetic Engineering & Biotechnology News put together a list (found here) of potential COVID-19 treatments in development.
Animal Research on the Front Lines
“Daewoong Pharmaceutical, a major bioengineering company in South Korea, will carry out the first phase of clinical trials in Indonesia for COVID-19 respiratory symptom treatment using mesenchymal stem cells after drug efficacy tests using animal models have identified anti-inflammatory and antiviral effects,” the article said.
“Animal research suggests COVID-19 vaccines could prevent serious disease but may not completely block infection. One study showed vaccinated animals avoided being infected with pneumonia but had some virus left in their noses and throats,” the article noted.
“The company has submitted data to DCGI based on animal trial, they conducted. Animals like- mice, rabbits, guinea pigs, rats were used and these animals developed antibodies against the virus,” mentioned a report.
“Dr. Donald Alcendor, an associate professor of microbiology and immunology at Meharry Medical College, began working on the COVID-19 antiviral in April and anticipates it is four to six weeks away from animal toxicity testing,” the report said.
“We have already completed the first round of preclinical animal testing and the results were quite encouraging,” University of Houston biology and biochemistry professor Zhang said. “I think there is no doubt that more research is needed for any vaccine development.”
“Scientists may be able to rule out these alternative explanations with more rigorous statistical analyses or a controlled experiment in an animal population,” WaPo reported.
“Antroquinonol was found to reduce viral nucleic acid replication and viral protein synthesis in both cell and animal experiments,” the press release said.
“Inovio … said INO-4800 provided ‘full protection’ from SARS-CoV-2 replication in the lungs of mice,” the article said.
“It’s extremely important to have safe and effective vaccines available for everyone in this country,” Fauci said in opening remarks before a Senate committee on June 30. He emphasized that researchers have made significant headway on experimental vaccines and therapies for COVID-19 thanks to preclinical vaccine and therapy trials with animal models.
“But we are cautiously optimistic, looking at animal data and the early preliminary data, that we will at least know the extent of efficacy sometime in the winter and early part of next year. … Hopefully, there will be doses available by the beginning of next year,” he said.
“In addition to positive interim Phase 1 data, INO-4800 has been shown to protect mice in SARS-CoV-2 viral challenge studies, where vaccination with INO-4800 prevented viral replication in the lungs of animals challenged with SARS-CoV-2,” the article said.
“In addition to positive interim Phase 1 data, INO-4800 has been shown to protect mice in SARS-CoV-2 viral challenge studies, where vaccination with INO-4800 prevented viral replication in the lungs of animals challenged with SARS-CoV-2,” the press release said.
Dr. Anthony Fauci testified during a Senate committee hearing and mentioned animal data.
“In addition, Inovio said that in a preclinical animal study, INO-4800 provided full protection against coronavirus replication in the lungs in mice that were infected with the virus,” the article said.
“Those within the industry say the company seems to have achieved vaccine stabilisation and completion of animal studies in record time considering that it was only on May 9, 2020 that the ICMR announced collaboration with Bharat Biotech ‘to develop a fully indigenous vaccine for COVID-19 using the virus strain isolated at ICMR’s National Institute of Virology (NIV), Pune,'” the article said.
“In earlier animal testing of the vaccine, which is produced in tobacco plants, mice began producing a positive antibody response within 10 days of receiving a single dose, researchers said in May,” the report noted.
“On April 30, Vaxart disclosed that it obtained positive preclinical results for its COVID-19 vaccine candidates, with ‘several’ of the candidates generating immune responses in all tested animals after a single dose,” the report said.
“Between the preclinical data from animal models and the retrospective data from humans, we felt there was good rationale to test this concept with COVID-19,” said Chetan Bettegowda, a professor of neurosurgery at the Johns Hopkins School of Medicine.
New Hampshire Democratic Sen. Jeanne “Shaheen and the other senators also noted that the Agency for Toxic Substances and Disease Registry (ATSDR) issued a ‘Statement on Potential Intersection between PFAS Exposure and COVID-19’ earlier this month,” the report said.
“This statement indicated that ‘there is evidence from human and animal studies that PFAS exposure may reduce antibody responses to vaccines … and may reduce infectious disease resistance,’” Shaheen and other senators wrote.
“The Chulalongkorn project employs new mRNA vaccine technology and the team expects final results from the animal-testing stage in the next two weeks,” the article said.
“Animal research suggests COVID-19 vaccines could prevent serious disease but may not completely block infection. One study that dripped the coronavirus into monkeys showed vaccinated animals avoided pneumonia but had some virus lurking in their noses and throats,” the report said.
The company had successful trials with mice, rats, rabbits and pigs.
“A possible vaccine for the new coronavirus has shown good enough results in animals to attract federal money to take it to the next level, but the Colorado State University researchers involved caution that it has many hurdles to clear before going to the public. CSU’s labs have produced a small amount of a vaccine and tested it on hamsters, said Ray Goodrich, executive director of the university’s Infectious Disease Research Center,” the article said. “The hamsters have formed an immune defense and don’t get sick if they’re exposed to the virus, but not everything that looks promising in small animals works as well in humans.”
“The research is part of an ongoing and broader collaboration between Tonix and Southern Research to develop and conduct animal testing of Tonix’ TNX-1800, which is a live replicating virus vaccine designed to protect against COVID-19. The data will support the interpretation of animal trial results with TNX-1800, which are expected in the fourth quarter of 2020 and subsequent human trials,” the post said.
SDSU Assistant Professor of Mechanical Engineering Kevin “Wood has been in touch with physicians in Tijuana and officials at COFEPRIS (Mexico’s equivalent of the FDA) about getting the device approved for use in Mexico. That will likely involve additional animal experiments, he says,” the article said.
“There was never a coordination to this level, where we would be using a master protocol and harmonizing as much as we can across centers with shared controls,” said Jay Rappaport, a leader of ACTIV’s nonhuman primate work.
University of Ottawa plant biologist Allyson “MacLean’s work will be tested on mice in collaboration with John Bell of the Ottawa Health Research Institute,” the post said.
The company’s vaccine is in a nonhuman primate study.
“The firm said that its oral COVID-19 vaccine candidate would be involved in a nonhuman primate challenge study and that it was ‘the only oral vaccine being evaluated’ in the program,” the article said.
“Further to this, [researchers] explain that in mice, ‘removal of certain gut bacteria by antibiotic[s] leads to increased susceptibility to influenza virus infection in [the] lungs,’” the article said.
“In those animals that did not receive the vaccine, we saw high levels of virus present in the lungs, present in the trachea, present in samples that we took from various organs within the body. In the groups that were vaccinated, there’s no evidence of adverse effects and no evidence the disease has actually been occurring,” said Ray Goodrich, director of the Infectious Disease Research Center at Colorado State University.
“Animal studies of a potential COVID-19 vaccine have been so encouraging that researchers plan to speed up testing of the vaccine in humans,” the article said.
“According to the researchers, statins may serve such a purpose because these drugs slow the progression of lung injury in animals, improve immune cell responses, and strongly reduce inflammation, which is likely responsible for severe Covid-19 complications such as organ damage,” the article said.
“Only if a certain vaccine surpasses the animal testing phase is it allowed to proceed to clinical trials on humans,” the article said.
“It usually takes about two years to bring a new drug to market, even after large clinical trials are underway, although priority drugs can advance faster, she said. It’s an elaborate process, involving lab tests, animal experiments and human trials, plus ensuring that adequate production facilities, quality control and distribution chains are in place,” the article said.
“The virus also attacked pancreatic organoids that had been transplanted into mice, and cells in liver organoids. … The organoid study adds strength to the argument that SARS-CoV-2 might cause or worsen diabetes, but the paper itself is not enough to prove the link, says [scientist Abd] Tahrani,” the article said.
“One Duke researcher in Singapore who is working on a vaccine said they are in the animal testing phase right now, but hope to move to clinical trials soon,” the report said.
“The antibodies were introduced in the mice 12 hours after the viral challenge. The experiment showed that the antibody treatment reduced the amount of virus in the animals by 32.8% for one of the antibodies and 26% for the other, when compared to a control group three days post-infection,” the article said. “The animals treated with each antibody also had fewer lung lesions than the placebo control animals.”
“The studies demonstrated that vaccination with INO-4800 generated robust binding and neutralizing antibody as well as T cell responses in mice and guinea pigs,” Inovio Pharmaceuticals said in a statement.
June 23: ‘ACE2 and TMPRSS2 variation in savanna monkeys (Chlorocebus spp.): Potential risk for zoonotic/anthroponotic transmission of SARS-CoV-2 and a potential model for functional studies,’ PLOS One
“In this new study, the research group from The Pirbright Institute, the Jenner Institute of the University of Oxford, University of Surrey, Rutherford Appleton Laboratory Harwell Oxford and Public Health England decided to test the immunogenicity of either one or two doses of AZD1222 vaccine in mice and pigs in order to inform clinical development additionally,” the article said.
“Thai scientists administered a second dose of an experimental COVID-19 vaccine to monkeys on Monday, looking for another positive response to enable clinical trials in humans as early as October,” the report said.
“A team of scientists led by Dennis R. Burton from the Scripps Research Institute has discovered that neutralising antibodies present in the blood of COVID-19 infected who have recovered offers powerful protection against novel coronavirus in animals,” the article said.
“Alongside the findings published in Science, Australian evolutionary experts from the University of Sydney and University of Melbourne have published a complementary Perspective, proposing that similarly refining research about when COVID-19 and other zoonotic diseases emerged will assist in understanding how such pathogens jump from animals to humans,” the article said.
“This is also the first clinical trial in the world of therapeutic mAb in healthy people after evaluation in a non-human primate model,” the report said.
“In order to identify host genes indispensable for cell survival in response to SARS-CoV-2, this group of researchers decided to use the African green monkey cell line Vero-E6, which is highly amenable to SARS-CoV-2 infection and virus-induced cytopathic effects,” the article said.
“The partners formed an alliance in March this year to develop a vaccine against Covid-19 using Tonix’s horsepox vaccine platform. They agreed to develop and conduct animal testing of TNX-1800, a live modified horsepox virus vaccine formulated for percutaneous administration,” the article noted.
“Preliminary results in animal studies have so far proven successful,” the article said.
“What do Covid-19, Ebola, Lyme and AIDS have in common? They jumped to humans from animals after we started destroying habitats and ruining ecosystems,” the story said.
“Wyss [Institute] researchers have already identified promising compounds that are currently being tested by collaborating labs in human organ chip technologies and animal models, and the team is continuing to evaluate many more drugs,” the report said.
“In a new study, researchers examined the antiviral effect of hydroxychloroquine in macaques (a type of monkey) infected with the COVID-19 virus, used alone or in combination with drug azithromycin,” the report said.
“In cells and animal models, SARS-CoV-2 induced abnormally low levels of transcripts downstream of type I and type III interferons, juxtaposed with high levels of cytokines such as IL-6, Benjamin tenOever, of the Icahn School of Medicine at Mount Sinai, and his colleagues recently reported,” the article said.
“The study demonstrates the rapid process of isolating, testing and mass-producing antibody therapies against any infectious disease by using both genetically engineered mice and plasma from recovered COVID-19 patients,” the press release said.
“After lab testing, researchers move to animal testing and ultimately to humans,” the article said.
“Our data certainly implies that it will be more transmissible, but more animal experiments will be necessary,” Dr. Hyeryun Choe said.
“Eijkman Institute director Amin Soebandrio said animal testing was to ensure that the vaccine’s antigens could form antibodies in humans, which could help protect them from COVID-19. … Animal rights organizations have voiced their objections to animal testing despite researchers ensuring that they will adhere to ethical norms,” the article said.
“INO-4800 evidence has been well-tolerated first in preclinical studies in mice, and then in the first cohort of 40 participants in the Phase I stage of the study,” the article said.
“Moderna Inc., which is developing what is considered to be the lead candidate, for example, was given permission to begin testing in humans before waiting until testing in animals was complete. Animal testing is ongoing,” ABC reported.
University of Sao Paulo immunologist Gustavo Cabral de Miranda’s “group is starting animal testing, and some other COVID-19 vaccine candidates in preclinical evaluation are following a similar approach,” the article said.
“N.C. A&T said it plans to use the funding for multiple projects, from studies in both food and animal testing, affordable fever detection in K-12 schools, ways to cut down death rates among the elderly in assisted living facilities and the development of a nanoparticle that can kill the virus,” the article said.
“We believe that animal studies, including mice and monkeys, will show that the LSU patented vaccine is much more efficacious in conferring long-term responses to the virus,” Dr. Gus Kousoulas said.
“Remdesivir is an antiviral medication developed initially by U.S. biopharmaceutical company Gilead Sciences to treat Ebola. It wasn’t effective, but during animal testing it had shown promise treating SARS and MERS, both of which are coronaviruses,” the report noted.
“But with animals, researchers can ‘challenge’ those that are vaccinated or have had an initial infection to see if they can ward the virus off — which is what recent studies in monkeys demonstrated. Scientists found that the animals generated neutralizing antibodies after they first contracted the virus or when they were given experimental vaccines, and that the higher the level of the antibodies the monkeys had (the higher the ‘titer,’ in scientific parlance), the more protected they were against the pathogen when scientists sprayed a second dose into their noses,” STAT noted.
“This is a significant concern because despite many years of research on other human coronaviruses such as SARS‑CoV and MERS‑CoV, no vaccines of any kind have been approved. Another major concern is that some experimental vaccine studies in animal models suggest that insufficient protective immunity against coronaviruses such as SARS‑CoV may induce enhanced susceptibility to respiratory disease,” UConn vaccine researcher Paulo Verardi said. “In other words, inadequate or weak vaccines may not only lead to poor protection but also to vaccine-enhanced disease in COVID‑19 patients.”
“It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2,” the article’s summary said. “Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2).”
“In an experiment led by Castle professor of medicine and professor of immunology Dan Barouch, animals exposed to the virus a second time five weeks later developed no clinically observable symptoms and displayed immunologic control of the disease,” the article said.
“We have a lot of confidence based on what we’ve see so far based on our animal modeling that the vaccine will work,” said Gregory Glenn, president of research and development at Novavax.
“In a June 2 presentation, Novavax showed that NVX CoV2373 induced animals to produce neutralizing antibodies against SARS-CoV-2 and that titers increased at least eightfold following a second vaccination. The company also showed that Matrix-M enhances immunogenicity,” the article noted.
“Organoids can do a lot — but not everything, [Josef] Penninger [a medical geneticist at the University of British Columbia in Vancouver] acknowledges: ‘This will not replace animal models,”’ the article said.
“When judged based on animal test results, candidates introduced through this technology transfer are likely to be developed as therapeutic agents that are effective against various viruses that have undergone mutation,” LegoChem Bioscience CEO Kim Yong-joo said.
“Scientists at the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center have created a fingertip-sized skin patch that is also showing promising results in animal testing,” the article said.
The Times held a virtual round table discussion with a virologist, a vaccine scientist, an immunologist and oncologist, a biotech scientist and inventor, and a former head of the Food and Drug Administration.
“An ideal animal model is one that reproduces the human disease as closely as possible — in which, for example, clinical signs resembling symptoms in humans are observed, virus replication is observed in similar organs, immune response mirrors that in humans and so on. In addition, an animal model is often used to demonstrate whether a virus can be transmitted from an infected to an uninfected animal,” said Susan Weiss, a microbiology professor at the University of Pennsylvania. “Scientists use animal models to understand how the virus causes disease.”
Animal research is an important part of the vaccine testing process.
“It’s not clear how the virus invades the brain, said [Dr. Karima] Benameur. Some speculate it could be through the olfactory nerve, which might explain why some patients lose their sense of taste and/or smell,” the article said. “Benameur noted that animal research shows that when the virus is injected into nose fibers, it can travel to the brain.”
“Scientists had for years been finding viral strains in bats and other animals that were genetically similar to the virus behind the SARS epidemic. But sequence data has its limits,” the article said.
“Nearly all emerging pathogens like COVID-19 come from ‘zoonotic transfer’ — essentially, when a virus present in animals jumps to infect humans. … Zoonotic diseases are particularly complex because they overlap multiple sectors — environment, agriculture, and health — that are often siloed from one another,” the article said. “Dr. [Simon] Reid says his dream project would bring together researchers with knowledge of across multiple fields, including from human and animal medicine, ecology, sociology, microbiology and those who study the transmission of pathogens in humans, wildlife, and livestock.”
“The trial involved the drug to be administered for a maximum of 14 days to coronavirus patients between 20 and 74 years old with mild pneumonia. The study excludes pregnant women due to side effects shown in animal testing, [a Fujifilm spokesman] added,” the report said.
“Many scientists agree that our behaviour – particularly deforestation and our encroachment on diverse wildlife habitats – is helping diseases to spread from animals into humans more frequently,” the article said.
“The phase I clinical trial will test the safety and dosage of the neutralizing antibody among healthy people, and this is a clinical trial for the world-first neutralizing antibody treatment against COVID-19 among healthy people after non-human primate experiments,” the article said.
“STI-4398 COVIDTRAP protein and STI-1499 neutralizing antibody have shown efficacy in an in vitro cellular infection model for SARS-CoV-2 established in our laboratory and these results justify now the progression into animal studies. We are planning to submit all preclinical data for scientific publication in the next two to three months,” said Dr. Slobodan Paessler.
The article focuses on the gradual resumption of research in animal laboratories in the U.S. as the preliminary stages of reopening get underway.
“SARS-CoV-2 came from an animal but finding which one will be tricky, as will laying to rest speculation of a lab escape,” Nature noted.
“The directors also plan to expand the program by obtaining additional grants that they can use to begin coronavirus research,” the report said.
This article highlights the impact the COVID-19 pandemic is having on research using animal models, including research to find cures for rare diseases.
“Phase 1 studies look at both dose size and, if animal studies suggest two doses might be needed, then they also look at one dose versus two doses,” said Dr. Kelly Moore, associate director of immunization education for the Immunization Action Coalition.
“After testing a vaccine in animals, developers must show it’s safe and effective in humans,” the article said.
“Studies in animals and cell cultures in the lab show it may also help suppress the aggressive immune reaction that doctors have seen in some patients’ lungs and respiratory systems. That suggests that by the time a COVID-19 patient is hospitalized, it might be too late for hydroxychloroquine to help, since the infection is already well underway,” the report said.
“The potential for the use of interferons in coronavirus infections was examined in the earlier outbreaks of SARS and MERS. In vitro experiments showed that interferons did have antiviral activity on the SARS-CoV, especially IFN-β and IFN-γ, and for IFN- β, against MERS-CoV as well,” the article said. “Follow-up animal experiments showed that IFN-β had higher antiviral activity against MERS CoV compared to the lopinavir-ritonavir combination.”
“This is very promising. But of course it is an animal study, so we want to translate that really compelling result into humans,” King’s College London neuroimaging and psychopharmacology professor Mitul Mehta told the PA news agency.
The company will move to clinical trials after testing in animals.
“Even before COVID-19, Gilead had tested remdesivir against other coronaviruses — including those that cause SARS and MERS — in laboratory and animal studies,” the report noted.
“Why are animal models so important? Because there are many other factors that could affect antibody efficacy in a living organism that can’t be simulated in a petri dish,” the article said. “For example, how long are mAbs functional in the body and are they safe? Animal models can provide preliminary safety data. Beyond animal models, a key mAb property to consider is whether it can be efficiently manufactured in a stable, safe form for human use.”
“South Korea’s Celltrion Inc said on Monday its experimental treatment of COVID-19 demonstrated an up to 100-fold reduction in viral load of the disease in animal testing, saying it aims to start in-human clinical trials in late July,” the report said.
“Japan approved Avigan as a flu drug in 2014. It has only been used as a backup treatment and not given to most patients, partly because animal testing showed it could potentially cause birth defects,” WSJ reported.
“In this study we used optical mapping to demonstrate the arrhythmic effects of [hydroxychloroquine (HCQ)] on [guinea pig] and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL),” the authors wrote.
Fact #2: “Animal research suggests COVID-19 survivors may gain immunity.”
“It will be important to demonstrate the potential for vaccine efficacy in early-phase clinical studies by measuring the induction of neutralizing antibodies and in animal models by demonstrating protection against virus replication and disease,” the article said.
“Although vaccines are usually associated with very low risks, experimental vaccines might not protect participants and, in some cases, might even increase the severity of disease among those who are subsequently infected. These outcomes have occurred, for example, for vaccines against respiratory syncytial virus (46) and dengue virus, (47) in some cases resulting in small numbers of deaths among participants in vaccine research,” the article said. “This kind of danger might apply to coronavirus vaccines, because vaccine-enhanced disease has been observed in animal challenge studies with coronaviruses (12).”
“Since each lab is different, the procedures will vary. For example, the animal research labs cannot allow researchers into the lab past a certain time or it will interfere with the circadian rhythms of the animals — making it difficult to have multiple shifts,” the report said.
“Research on COVID-19 patient samples has shown the presence of two antibodies that inhibit viral RBD-ACE2 binding. Animal experiments have shown that these could reduce the viral load in the lungs of infected mice,” Dr. Liji Thomas wrote.
Scientists “are connecting hypothetical dots based on past studies of experimental vaccines for previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), in which some immunized animals developed more severe disease,” the report said.
“The Swiss drugmaker’s gene therapy unit AveXis is already making test batches of the vaccine and plans to start producing doses later in the summer that can be used for a clinical trial, said Dave Lennon, the unit’s president. … The Novartis unit has so far committed to manufacture doses for animal studies and a phase 1 trial, free of charge, Dr. Lennon said,” WSJ reported.
Researchers working with rhesus macaques published results in Nature on May 26.
Novavax started clinical trials for a coronavirus vaccine candidate, NVX-CoV2373, in Australia. Animal tests showed positive results in low doses.
“Oxford University in England and Maryland-based vaccine company Novavax seem ahead of the global race as their vaccine candidates have shown success in animal trials,” USA Today noted.
Researchers working with rhesus macaques found the first human neutralizing monoclonal antibody for COVID-19.
Merck Research Laboratories President Roger Perlmutter reportedly said the company plans to look at EIDD-2801’s cancer-causing potential in reproductive and developmental biology animal studies.
“In remdesivir’s case, government researchers narrowed the search from 1,000 compounds to the chemical that would become remdesivir, confirmed its potency in laboratory tests, tested it in monkeys, and finally sponsored a pivotal clinical trial in humans,” the report said.
“In the preclinical phase, researchers use cells and animals to assess safety and produce evidence of clinical promise, evaluated by the candidate’s ability to elicit a protective immune response,” a GAO report said.
“While it will be some months before we know whether any of the proposed vaccines are effective, initial safety trials and encouraging animal studies show promising early signs,” ABC noted.
“In mice, the vaccine provided full protection against viral replication in the lungs, which researchers tested by giving mice the vaccine and then deliberately infecting them with the virus,” The New Yorker reported about Moderna’s experimental vaccine. “(Scientists place a small drop of virus-laced fluid over the mouse’s nostrils. Similar trials on rhesus macaques are about to start.)”
The report said:
“‘This is promising data, but it’s early data,’ said Dr. Dan Barouch, director of vaccine research at Beth Israel Deaconess Medical Center in Boston, who was not involved in the work. ‘Over all, I would say this is good news.’
… And on Wednesday, Dr. Barouch and his colleagues published a study showing their prototype vaccine protected monkeys from coronavirus infection.”
“Three studies published Wednesday suggest it should be possible to come up with a coronavirus vaccine — tests performed on animals have shown the right results to prove a vaccine could be possible,” NPR reported.
Two studies published in Science found antibodies to SARS-CoV-2 provide some level of immunity in rhesus macaque monkeys, though it is unknown how long protection lasts.
“In one of the studies, nine rhesus macaque monkeys, which share 93 percent of the same DNA as humans, were injected with SARS-CoV-2, the virus that causes COVID-19. The virus quickly spread and all of the animals developed viral pneumonia, though all of them recovered within 28 days,” The Hill reported.
“Our partnership with Bharat Biotech will accelerate our vaccine candidate through the next phases of development,” Jefferson Vaccine Institute Director Matthias Schnell said. “We will be able to complete animal testing and move to a phase 1 clinical trial [in humans] rapidly.”
“Animal studies have raised expectations, too. Researchers at Beth Israel Deaconess Medical Center on Wednesday published research showing that a prototype vaccine effectively protected monkeys from infection with the virus,” the article said. “The findings will pave the way to development of a human vaccine, said the investigators.”
“Once they’ve determined an animal’s coronavirus symptoms, [Utah State University Professor Brett] Hurst said they can treat the animals with the drugs that proved to be successful in the human-cell model,” the report said.
“Another thing that was similar to humans is that most of the animals [primates] didn’t get sick, visibly ill, but there were a couple that did,” said Dr. Skip Bohm, chief veterinary medical officer of the Tulane National Primate Research Center.
“One way to find out whether vaccines can prevent transmission would be to study them in animals that are naturally susceptible to the virus and seem capable of spreading it, such as ferrets and hamsters, says [University of Pittsburgh Center for Vaccine Research aerobiologist Douglas] Reed,” the article said.
“When researchers identify the genetic sequence of a protein or enzyme that is essential to the virus’s replication, they then look for a compound that blocks it, called the inhibitor. The compounds are developed into a drug that not only lasts long enough in the body to kill the virus but is also nontoxic,” the report said. “Only then can it move to animal trials and, eventually, human trials.”
“CureVac said late last week that its lead COVID-19 vaccine candidate generated ‘high levels’ of virus-neutralizing titers in animal models and that it ‘has the potential to induce a strong immunologic response to neutralize SARS-CoV-2,'” the report said.
Two Lawrence Livermore National Laboratory researchers will collaborate with scientists from the University of New Mexico and the Tulane National Primate Research Center.
“Lab researchers see the [nanolipoprotein particles] NLPs platform as a flexible tool that can broadly be applied to developing vaccines for different pathogens,” the press release said.
The article said:
“‘These interim phase 1 data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 µg,’ Dr. Tal Zaks, the chief medical officer at Moderna, said in the statement. When combined with data from the mouse study, these results ‘substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.’”
“The neutralizing antibody and safety results from the Phase 1 clinical study are promising for the Moderna mRNA vaccine candidate and supportive to proceed forward with the planned Phase 2 studies,” RenovaCare Chief Scientific Officer Robin Robinson told STAT.
The health-oriented news website reported: “Vaccination with the candidate vaccine, provisionally labeled mRNA-1273, also prevented viral replication in the lungs of mice in preclinical testing, the [Moderna’s] statement said.”
“Chinese researchers have successfully identified multiple highly potent neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19, from convalescent plasma by high-throughput single-cell sequencing, according to a new study published in Cell on Sunday. … New results from animal studies showed that neutralizing antibodies provide a potential cure for COVID-19 as well as a means for short-term prevention, which marks a major milestone in the fight against the pandemic,” the report said.
“It costs quite a bit of money to run phase one and two studies, and you might be halfway through that when you show your animal has no protection,” Director of the Peter Doherty Institute for Infection and Immunity Sharon Lewin said.
“Before you move [the vaccine] into the human, […] you need to work in multiple animal models, which takes time, to show that not only were you able to show that it’s safe, but that in the event that that individual got infected, it stopped the infection from causing a clinical disease or at least reduced the clinical symptoms,” said Kristin Grimsrud, the associate director of vivaria and veterinary care at UC Davis’ Mouse Biology Program.
Research has shown that diseases such as malaria have a distinctive odor and also that respiratory disease can change the body’s odor. Scientists are working to determine if medical detection dogs can detect COVID-19 in humans.
“The ‘spike’ proteins of both SARS-CoV and SARS-CoV-2 are related and they attach to the same molecule called ACE 2 on human cells to infect people. We now also know through animal experiments with SARS-CoV-2 that neutralising antibodies protect from reinfection,” University of Melbourne professor Kanta Subbarao wrote in an article.
This Washington State University press release announced the development of an antibody that successfully neutralizes protein A9, a protein that triggers inflammation, including severe pneumonia in COVID-19 patients. University researchers discovered the specific role of this A9 protein by doing research with mice and studying the A9 protein in mice. Then they were able to develop an antibody.
A Korean placenta injection showed positive results in a ferret model.
The White House will soon announce its “Operation Warp Speed” to speed up the development of a COVID-19 vaccine. “The project, vaguely described to date but likely to be formally announced by the White House in the coming days, will pick a diverse set of vaccine candidates and pour essentially limitless resources into unprecedented comparative studies in animals, fast-tracked human trials, and manufacturing,” the article said.
“A Korean research team has developed a new vaccine platform using RNA-based adjuvants for the Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), which showed promise in nonhuman primates,” the publication reported.
“Researchers from the Emory Consortium for Innovative AIDS Research in Nonhuman Primates and their colleagues across North America have shown a new HIV vaccine is better at preventing infection and lasts longer, continuing to protect one year after vaccination. The findings, which are published online today in Nature Medicine, provide important insights for preventing HIV, and the timeliness of the results could also help shape the scientific community’s approach to developing vaccines for COVID-19,” a press release said.
“Recent research shows that ferrets, cats and golden Syrian hamsters can be experimentally infected with the virus and can spread the infection to other animals of the same species in laboratory settings,” the Q&A article said.
“Mairi Noverr of Tulane University School of Medicine along with Monica Vaccari and Tracy Fischer of Tulane National Primate Research Center all received Fast Grants for COVID-19 research,” according to the university.
On May 7, Extra TV’s Billy Bush sat down with Dr. Armand Dorian to discuss the latest headlines surrounding COVID-19. They discussed the University of Oxford’s successful COVID-19 vaccine trials with rhesus macaques. This allowed Oxford University to move into human trials in late April. Watch the Extra TV segment to learn more! Video credit: Extra TV
“In animal studies, Q-griffithsin worked against Ebola, hepatitis, MERS, SARS and other viruses,” the report said.
“Fauci has said that he thinks a final vaccine could be available for general use as early as January, which would break records for the speed at which previous vaccines were developed,” National Geographic reported. “One reason for his confidence is the ‘impressive’ results being seen now in animals tested with a vaccine candidate made by Cambridge, Massachusetts-based Moderna Therapeutics, which brought it into human trials in a record 42 days.”
Researchers at two Harvard-affiliated hospitals have studied their vaccine candidates in mice. The team expects to test for safety in monkeys in about a month.
“Animal research does suggest that SARS-CoV-2 antibodies may appear and confer some immunity,” the article said.
“Verndari, Inc. is also in discussions with the California National Primate Research Center at UC Davis to conduct further testing in nonhuman primates,” the article said.
“Vaccine development takes a long time. There has to be rigorous testing in different animal models, and then small-scale studies in humans,” said microbiologist Karl Klose, director of the South Texas Center for Emerging Infectious Diseases and professor of microbiology at UTSA. “The process is designed to ensure the safety of the people who take the vaccine. We will learn a lot from this process, including how to use a live vaccine platform to protect against an emerging disease. Hopefully in the future, we can respond quicker with a vaccine against the next pandemic.”
“Verndari, Inc., a biopharmaceutical company based in Napa, will begin preclinical testing of a possible coronavirus vaccine on mice this week in partnership with UC Davis’ mouse biology program,” the report said.
“This is gonna be a critical piece. It’s like you can’t fight a war without tanks,” said Dr. Ed Liu, president and CEO of The Jackson Laboratory. “You can’t fight a war, this war, the pandemic, without a model system to test whether the drugs or the vaccines work.”
“Our article published today shows that a single injection of our Ebola vaccine provided 100% protection for mice exposed to Ebola virus” said Flow Pharma Chief Science Officer Charles Herst, the first author on the article. “By relying on killer T-cells rather than antibodies, FlowVax Ebola is able to attack the nucleocapsid protein located at the center of the virus where antibodies cannot reach. We are taking the same approach with FlowVax COVID-19.”
“Scientists at the National Institutes of Health’s Rocky Mountain Laboratory in Montana last month inoculated six rhesus macaque monkeys with single doses of the Oxford vaccine. The animals were then exposed to heavy quantities of the virus that is causing the pandemic — exposure that had consistently sickened other monkeys in the lab,” the report said. “But more than 28 days later all six were healthy, said Vincent Munster, the researcher who conducted the test.
‘The rhesus macaque is pretty much the closest thing we have to humans,’ Dr. Munster said, noting that scientists were still analyzing the result.”
Beijing-based Sinovac Biotech’s COVID-19 vaccine-in-development showed promise in rhesus macaques, scientists reported.
This joint statement is the result of a collaboration between several research advocacy organizations along with individual biomedical researchers, animal care experts and university communicators.
“Ciclesonide is used to treat inflammatory disesaes such as asthma and allergic rhinitis. It is marketed under the brand names Alvesco for asthma etc. It was patented in 1990 and approved for adults and children 12 and over by the FDA in 2006,” the article said. “Regarding the molecular mechanism underlying its anti-inflammatory effect, it is most likely that this hormone blocks PAK1, mainly for following reasons: (i) first of all, inflammation in general requires PAK1 , and in PAK1-null mutant of mice no inflammation takes place , (ii) ciclesonide (10 mg/kg/day) almost completely suppresses the PAK1-dependent growth of lung cancer (A541 cell line) xenografts in immune-deficient mice as well , and (iii) this hormone was recently shown to block both PAK1-dependent replication and pathogenesis (fibrosis = lung inflammation) blocks COVID-19 pathogenesis clinically : https://writening.net/page?FC3QPm.”
“Investigators at Rocky Mountain Labs tested [remdesivir] in a non-human primate model, a SARS-Coronavirus Type 2 or Covid-19,” said RML’s associate director for scientific management, Dr. Marshall Bloom. “They found that this drug had significant affect in ameliorating the course and severity of COVID-19 infections in non-human primates, if given early enough during the course of the disease.”
“We have seven scientists and a staff of over 30 people working overtime on establishing [nonhuman primate] animal models,” Texas Biomed President and CEO Larry Schlesinger said.
“Remdesivir is one of the unique compounds that actually gets stuck and makes the replication complex stop in its tracks,” Dr. Robert Gottlieb told KERA. “It has been used against SARS in vitro, and actually that’s why it became such a good lead compound with the current epidemic. … We’ve studied [SARS-CoV-1] and some similar viruses like [MERS] … both in small animals as well as in larger animals, and this remdesivir seems to work just fine in those cases.”
“Veterinary diagnostic labs across the country are developing their own tests for Covid-19, and many use the same basic processes that human tests do,” the article said.
“In order to assess vaccine efficacy, COVID-19 specific animal models are being developed, including ACE2-transgenic mice, hamsters, ferrets and non-human primates. Biosafety-level 3 containment measures are needed for animal studies involving live-virus challenges, and the demand for these capabilities is likely to require international coordination to ensure that sufficient laboratory capacity is available,” the article said.
“Flow Pharma, Inc., a San Francisco Bay Area biotechnology company developing the FlowVax(TM) peptide vaccine platform technology, today announced that researchers at the University of Texas Medical Branch at Galveston (UTMB) will begin testing Flow Pharma’s FlowVax COVID-19 vaccine candidate by challenging nonhuman primates with SARS-CoV-2, the virus that causes COVID-19 in humans, after the animals are vaccinated this month with FlowVax COVID-19,” a press release said.
“When you talk about developing a vaccine for millions of people, safety is an enormous priority,” said Dr. Mark Poznansky, director of the Vaccine and Immunotherapy Center at Massachusetts General Hospital.
Scientists from Emory University in Atlanta; the University of North Carolina at Chapel Hill; and Vanderbilt University Medical Center in Nashville, Tennessee, reported promising results after testing the drug EIDD-2801 on mice infected with coronaviruses similar to the one that causes COVID-19.
“In animal tests against SARS and MERS, diseases caused by similar coronaviruses, the drug helped prevent infection and reduced the severity of symptoms when given early enough in the course of illness,” the AP reported.
The Tulane National Primate Research Center in Louisiana will study COVID-19 in three species of nonhuman primates and evaluate potential COVID-19 vaccines and treatments in the nonhuman primate species that most closely mimics the progression of the disease in a human.
The World Health Organization cleared potential coronavirus vaccines for animal testing. Researchers in Australia have inserted vaccine samples into ferrets. “Australia’s Commonwealth Scientific and Industrial Research Organization (CSIRO) says its tests will be the first comprehensive pre-clinical trials of the vaccines to use an animal model,” the article said.
A team at the University of Pittsburgh School of Medicine is working on a potential COVID-19 vaccine. It’s shown promise during initial tests in mice, scientists said.
“We already have a lot of data on the safety of the vaccine candidate, because the necessary preclinical studies in nonhuman primates and animals have already been carried out,” J&J research chief Paul Stoffels said in an interview with the German newspaper Tagesspiegel.
“Researchers will use the funds to amplify efforts to investigate how SARS-CoV-2 – the virus that causes COVID-19 or the novel coronavirus – affects animals. Previously, research was limited to studying the effects on baboons, but now will include macaques, marmosets, mice, and guinea pigs,” the article said.
GeoVax is preparing to test three candidate vaccines for the novel coronavirus in animals, CEO David Dodd says. With funding from the Biomedical Advanced Research and Development Authority, GeoVax will use animal testing to zero in on the vaccine that is most likely to protect people from COVID-19, then scientists will test the most promising of them in clinical trials later this year.
Veterinarians don’t have evidence that pets can spread SARS-CoV-2, but they want more information, and several labs have developed veterinary tests. Shelley Rankin, a microbiologist at the University of Pennsylvania School of Veterinary Medicine, says if pets were readily susceptible to the virus, a spike would have been noticed by now, and the USDA and many experts warn against widespread testing of pets for COVID-19.
Scientists at the Tulane National Primate Research Center in Louisiana are working hard to fight COVID-19. ABC News gave an inside look at the challenges these researchers are up against.
About 82% of the 174.5 million doses of influenza vaccine distributed across the U.S. this season were produced in chicken eggs, according to the CDC, but the many chickens kept in secure facilities in the U.S. won’t be useful in developing a COVID-19 vaccine. Coronaviruses and influenza viruses have different receptors and other characteristics, and the novel coronavirus can’t replicate inside eggs the way influenza can, says pathology professor John Nicholls.
Researchers are studying antibodies to find out how to beat COVID-19. “If the antibodies work to protect cells from infection, then researchers will test them in animals exposed to the virus — to see if the proteins prevent the animals from getting sick, or, alternatively, if they can improve the health of animals that are sick with a version of COVID-19,” the report said.
“With about 15% of COVID-19 patients suffering from severe disease and hospitals being overwhelmed, treatments are desperately needed. So rather than coming up with compounds from scratch that may take years to develop and test, researchers and public health agencies are looking to repurpose drugs already approved for other diseases and known to be largely safe. They’re also looking at unapproved drugs that have performed well in animal studies with the other two deadly coronaviruses, which cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS),” the article said.
“We know that gorillas are very sensitive to human diseases,” Paula Kahumbu, chief executive of the Kenya-based conservation group WildlifeDirect, told the AP. “If anyone has a cold or a flu they are not allowed to go and see the gorillas. With coronavirus having such a long time of no symptoms in some cases, it means that we could actually put those gorillas at risk.”
“The University of Saskatchewan’s Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) is the first Canadian lab to develop an animal model for COVID-19 vaccine testing,” the article said.
Chloroquine phosphate, an 85-year-old antiviral drug that has previously been used for the treatment of malaria, and its derivative hydroxychloroquine have recently shown promising in-vitro results in primate cells infected with SARS-CoV-2. Chloroquine phosphate became the first-choice antiviral drug for malaria after researchers discovered it drastically reduced mortality in African penguins with avian malaria.
Monkeys are vulnerable to SARS-CoV-2. Primate center scientists are working to prevent colonies from infection.
Extensive studies in a variety of nonhuman primates, including macaques, led to the development of lopinavir and ritonavir as HIV/AIDS combination anti-retroviral drugs. In 2015, researchers discovered that lopinavir and ritonavir improved outcomes in marmoset monkeys infected with the MERS coronavirus (MERS-CoV). Since SARS-COV-2 and MERS-CoV are both coronaviruses and share many similarities, researchers launched a clinical trial of lopinavir and ritonavir in patients with COVID-19 in China.
The heads of two animal facilities spoke with the academic journal about how they are dealing with COVID-19.
Regeneron has developed hundreds of monoclonal antibody drugs that show potential for treating SARS-COV-2. Regeneron’s antibodies are produced in mice that have been genetically modified to have human-like immune systems.
Moderna and NIAID are currently investigating a potential messenger RNA vaccine for the new coronavirus. A clinical trial in humans has begun in Seattle for the mRNA-1273 vaccine. Despite reports to the contrary, the clinical trial began after mRNA-1273 was tested in mice.
Gilead Sciences’ antiviral drug remdesivir is currently being tested in five human clinical trials for its effectiveness against the new coronavirus (SARS-CoV-2). Pre-clinical research in laboratory mice and other animals demonstrated that remdesivir was effective against the MERS and SARS coronaviruses.
Doctors tested remdesivir on a critically ill patient with COVID-19 in California. An infectious disease specialist on the team treating the patient answered questions about the case. In February, Gilead and the National Institute of Allergy and Infectious Diseases (NIAID) published a paper demonstrating that remdesivir inhibited the replication of the coronavirus MERS in infected monkeys.
“It’s a basic rule of medical research: Before you inject anything into humans, conduct experiments on animals—frequently mice—to determine whether treatments are safe and effective. In the race to develop a vaccine for the new coronavirus, however, your everyday mouse won’t do,” Bloomberg correspondent Bruce Einhorn wrote.
“Given the urgency to stem the spread of the new coronavirus, some drugmakers are moving straight into small-scale human tests, without waiting for the completion of such animal tests.
‘I understand the importance of accelerating timelines for vaccines in general, but from everything I know, this is not the vaccine to be doing it with,’ Dr Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, told Reuters.”
Researchers will test potential vaccines in mice.
Preclinical tests involve research in animals to make sure a vaccine is safe. “If the vaccine protects in animal models, it can be made pure enough to be tested on humans,” Dr. Bart Haynes told USA TODAY.
“Animal research has played a critical role in virtually every medical advance over the last century,” said Matthew R. Bailey, president of the Foundation for Biomedical Research.
APN01 is a recombinant human Angiotensin Converting Enzyme produced by APEIRON Biologics that successfully blocked viral spread of SARS-CoV-2 and minimized lung injury when tested in laboratory mice. APN01 is now entering the clinical trial phase with COVID-19 patients in China.
The Detroit News published an opinion editorial written by FBR’s president on the importance of animal research in the search for a vaccine to control the coronavirus outbreak.
“We are working together to develop a plan to build out nonhuman primate models to test medical countermeasures such as vaccines and therapeutics,” said David O’Connor, professor at the UW School of Medicine and Public Health. “We want to make sure we are recapitulating the kind of clinical signs (of virus infection) that happen in people.”
We would like to say a word about the role of research animals in basic research to understand how COVID-19 infects humans and animals. A basic research study in macaque monkeys revealed that monkeys who recovered from COVID-19 developed some immunity to the SARS-COV-2 virus and did not get reinfected with the virus. Further basic research studies will be conducted to confirm these results. Several other teams of researchers are studying how the SARS-COV-2 virus jumped from animals to humans by using data from studies of other coronaviruses like SARS and MERS in bats, civets, pangolins, and camels. Here are a few good articles on basic research to understand the zoonotic transmission of COVID-19 from animals to humans:
“Researchers haven’t established that androgens control TMPRSS2 in the lung—ground zero for SARS-CoV-2 infection—as they do in the prostate; studies in lung tissue and cells from mice and humans come to conflicting conclusions,” the article noted.
These results come from the Tulane National Primate Research Center.
“Such chimeric mice would be very useful for studying COVID-19, which gravely impacts human, but barely affects mice,” State University of New York at Buffalo physiology and biophysics professor Jian Feng said.
“Further development of our technology could enable the generation of even larger quantities of specific types of mature human cells to allow us to create more effective mouse models to study diseases that gravely affect humans, such as malaria or COVID-19,” said professor Jian Feng.
Also, check out FBR’s white paper “The Critical Role of Nonhuman Primates in Medical Research” (linked here).
“In tests conducted at the Pasteur Institute in Paris, researchers found that when dextromethorphan was introduced into the cells of African green monkeys growing in petri dishes, the subsequent addition of SARS-CoV-2 resulted in more prolific viral growth,” the report said.
“We know from animal experiments that vaping itself — not even giving any drugs with it — can produce inflammatory changes in the lung,” National Institute on Drug Abuse Director Nora Volkow told Kaiser Health News.
Researchers, such as those at The Jackson Laboratory in Maine, are breeding transgenic mice. Experts will test different strains of transgenic mice as well as a variety of other laboratory animals including nonhuman primates to determine which ones are susceptible to infection with the virus.
“Every day, it seems another company announces an attempt to make its own virus-fighting vials. But to test an experimental formulation, scientists can’t just jump from Petri dishes into people,” STAT News reporter Eric Boodman wrote. “They need to try it in critters first, to check that the stuff is safe and effective.”
The Tulane National Primate Research Center launched a research project to understand COVID-19 with animal models. The researchers are trying to understand how the disease spreads and progresses in nonhuman primates.