Roundup: The Most Promising COVID-19 Vaccine Efforts

  • <<
  • >>

561875.jpg

 

The FDA approved the first vaccine for the prevention of Ebola on December 19, 2019—more than four years after the disease made its way from the Democratic Republic of Congo to the United States. Compared with COVID-19, Ebola was extremely tame, infecting only four people, killing one. Regardless, the need for a COVID-19 vaccine is clear; however, it will not happen tomorrow, next month, or even in a few months. All reports indicate the world is at least a year, most likely 18 months, away from a COVID-19 vaccine. While that may sound like a long time to others, scientists can read between the lines—researchers are working tirelessly to develop something to help the world in these trying times.

Since vaccine development is a long process, laboratories across the world find themselves at different development stages—which is not necessarily a negative. If, for instance, one of the vaccines developed first turns out not to work, there will undoubtedly be others waiting in the wings. First, let’s take a look at the vaccines furthest along the development chain:

  • Moderna, a biotechnology company based in Cambridge, Mass., has made perhaps the largest strides toward a coronavirus vaccine. On February 24, the company shipped vials of its vaccine, called mRNA-1273, to the National Institute of Allergy and Infectious Diseases (NIAID) to be used in the planned Phase 1 study in the U.S. mRNA-1273 is an mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein, which was designed by Moderna in collaboration with NIAID. The S protein complex is necessary for membrane fusion and host cell infection and has been the target of vaccines against the coronaviruses responsible for Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).
  • As of February 26, Novavax, a clinical-stage biotechnology company from Gaithersburg, Maryland, has advanced several vaccine candidates to animal testing. The company has produced and is currently assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing, which is expected to begin by the end of spring 2020. Novavax created the COVID-19 vaccine candidates using its proprietary recombinant protein nanoparticle technology platform to generate antigens derived from the coronavirus spike (S) protein. Novavax expects to utilize its Matrix-M adjuvant with its COVID-19 vaccine candidate to enhance immune responses.
  • Medicago, a Canadian biotech company that has received funds from DARPA, says it has produced a COVID-19 vaccine just 20 days after receiving the virus’s genetic sequence. However, the company uses plants as a bioreactor for growing vaccine protein rather than the traditional eggs. The unique technique is not yet approved by the FDA, so regulatory hurdles exist, including the need to go through clinical trials. That being said, Medicago CEO Bruce Clark said last week that if the hurdles can be cleared, the vaccine could become available November 2021.
  • Researchers in the Precision Vaccines Program (PVP) at Boston Children’s Hospital are on the front lines of developing a vaccine specially targeted toward older populations. Their strategy is to combine the coronavirus spike protein with adjuvants—small molecules added to a vaccine to boost the recipient’s immune response. In addition to a collection of known vaccine adjuvants, the team will test new adjuvants it has discovered in the PVP’s National Institutes of Health-funded Adjuvant Discovery Program. The group is already studying coronavirus responses in living animal models. Mice have been inoculated with a similar coronavirus spike protein derived from the SARS-2003 coronavirus with or without a lead adjuvant combination to get an early read on measuring an antibody response.
  • John Price, the CEO of Greffex, a genetic engineering company in Houston, said his company completed the development of a COVID-19 vaccine in late February. Rather than the live virus, Greffex's treatments use adenovirus-based vector vaccines, which are used to target various kinds of infectious diseases and cancers. Price said the company’s vaccine should move to animal testing soon. If the vaccine gets government approval, Greffex intends to give it away to the hardest hit countries.

Obtaining live samples of COVID-19 from the Centers for Disease Control and Prevention is the first step for laboratories and programs that produce vaccines the traditional way. Scientists at universities have begun that process and are gaining ground faster than usual.  

  • Scientists at the Colorado State University Infectious Disease Research Laboratory now have live strains of COVID-19 and are actively working to develop a vaccine. The first step for the team is to inactivate the COVID-19 virus, which they report they may be able to do as early as this week. Reports have indicated there is a possibility the first coronavirus vaccine will come out of CSU. The researchers are working extremely quickly, something the director of the lab attributes to the center’s experience working with similar respiratory viruses, like SARS and MERS.
  • Researchers at the University of Pittsburg expect to obtain live samples of COVID-19 in the coming weeks and will begin work to develop a vaccine immediately. The university’s Center for Vaccine Research has a stellar reputation, including development of the polio vaccine. It is a biosafety level 3 laboratory and has a team of scientists with significant experience working in aerobiology, biological imaging and immunopathology who investigate emerging infectious diseases and biodefense priority pathogens. It is one of the few labs nationwide qualified to handle pathogens like SARS-CoV-2.

Vaccines are critical to slow/halt COVID-19 now and in the future, there are other drug options, especially those that rely on drugs or molecules already approved by the FDA. While not always possible, this route removes the uncertainty of regulatory approvals.

  • On Monday, Regeneron Pharmaceuticals (Tarrytown, NY) and Sanofi (France) started a Phase 2/3 clinical trial evaluating Kevzara (sarilumab) in patients hospitalized with severe COVID-19. Kevzara is a fully-human monoclonal antibody that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19. The U.S.-based trial will begin at medical centers in New York, and will assess the safety and efficacy of adding Kevzara to usual supportive care, compared to supportive care plus placebo. The multi-center, double-blind, Phase 2/3 trial has an adaptive design with two parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infection across approximately 16 U.S. sites, and will evaluate the impact of Kevzara on fever and patients' need for supplemental oxygen. The second, larger part of the trial will evaluate the improvement in longer-term outcomes, including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.
  • The investigational drug remdesivir, developed by the University of Alabama at Birmingham, is already being used to treat select infected patients in the United States and in China who have been affected by COVID-19. Remdesivir, developed to treat the coronavirus causing MERS, was found to have significant activity against the COVID-19 strain when the outbreak began in the Chinese city of Wuhan. Importantly, remdesivir had demonstrated efficacy in treating other medically important coronaviruses MERS and SARS in cell culture and animal models. Based on the compassionate plea requests of treating physicians in the United States, Gilead Sciences released remdesivir for use in a few patients, although the drug has not yet been tested for safety or efficacy in these diseases.