News of vaccines under development to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have provided many people with the first sense of optimism for a future beyond the pandemic, and Dr. Trushar Patel, an associate professor in the Department of Chemistry and Biochemistry and Canada Research Chair in RNA and Protein Biophysics, counts himself in that crowd.
“We should be very positive and hopeful,” says Patel. “I’m so excited because, in the next few months, we will likely have an explosion of SARS-CoV-2 vaccines. There are about 48 vaccines in Phase 1, 2 and 3 trials. We have about 160 candidates in pre-clinical trials. We are looking at about 200 vaccines at different stages of development and they use different platforms.”
As the number of COVID-19 cases continues to rise around the globe, health-care systems are being put under extreme stress. The need for effective vaccines, with enough supplies for everyone, is crucial. The response must be global, Patel says, because the virus will keep circulating in countries without a vaccine, giving it the opportunity to mutate, completely change its structure and possibly come back as a new strain of virus.
He says he’s heartened by the response of the World Health Organization (WHO) and the global initiative to work with vaccine manufacturers to provide all countries with access to safe, effective, licensed and approved vaccines.
The recent announcements of vaccines by Moderna, Pfizer and BioNTech, AstraZeneca and the Gamaleya Center (Sputnik V) have brought new technology to vaccine creation. Traditional vaccines use viral proteins or an inactivated virus that cannot replicate. When injected, a person’s immune system begins developing antibodies that train the immune system to recognize the real virus in the future.
The new technology from Moderna and Pfizer uses messenger RNA (mRNA) from the spike proteins on the SARS-CoV-2 virus. An mRNA vaccine allows human cells to make a viral protein, or a piece of protein, that triggers an immune response. Four additional mRNA-based vaccines, currently in the early phase of clinical trials, are also being investigated.
Patel explains that human immunity has two different wings. The innate immune system is the first line of defense in any infection. The adaptive immune system develops a specific response for each type of pathogen and provides long-term systematic defense. As we grow, we encounter millions of pathogens in our lives and we develop antibodies that can then help us in the future with subsequent exposures. Vaccines are used to develop an adaptive immune response against a particular pathogen without causing disease.
“Researchers are using the mRNA that codes for the spike protein,” Patel says. “The idea is that the mRNA is delivered through different vehicles. For example, Moderna and Pfizer use lipid nanoparticles as carrier molecules to carry this piece of mRNA and deliver it to the human cells. The human cells then make the spike protein and that viral protein will raise immunity to protect us from future infections.”
Other vaccine candidates, such as AstraZeneca and Sputnik V, use adenoviruses, which have been genetically altered so they cannot replicate in the body, for drug delivery.
“People may be worried that corners have been cut to develop these vaccines,” says Patel. “I can say, based on the data available, that no corners have been cut in terms of study and producing these molecules, doing the laboratory tests and performing the clinical trials. This pandemic encouraged every layer, from scientists to the authorities to the regulatory bodies, such as the Food and Drug Administration, to work around the clock. Everybody pushed their best to come up to this stage. The data have shown the same short-term side effects as any vaccine, including mild fever and muscle pain.”
At this stage, the long-term side effects of an mRNA vaccine aren’t known. Because RNA molecules have a very short life, Patel expects few, if any, long-term side effects will occur. Vaccine developers will likely continue with Phase 4 clinical trials, known as post-market surveillance, to monitor what happens in the population over the longer term. The Phase 4 trials will further confirm or help refine the safety and efficacy of vaccine candidates. And, as cases of COVID rise in almost all parts of the world, there’s no time to waste.
Patel says he’s encouraged by the fact that more vaccines should be available early next year. Some of the vaccines, Moderna’s for example, require very cold storage because mRNA is an unstable molecule. That presents logistical problems, especially for countries where electricity and transportation are problems.
“It’s true researchers don’t know precisely how long immunity will last after someone has been vaccinated. We can’t wait for data, as we are going through a pandemic,” he says. “We need something that actually stops the spread of SARS-CoV-2 right now. If we keep this virus out of circulation for a year or two, that’s good enough. At this stage, I want something that is effective and efficacious, with no major side effects, that the population can take and can reduce the virus spread to the level that our health-care systems can cope with the cases that come in. Right now, we are averaging close to 1,600 cases in Alberta every day. Eventually our doctors, nurses and health-care providers, our ICUs, will reach the point that they cannot help everybody.”
In some of the forums Patel has been monitoring, people have voiced concerns that an mRNA vaccine will change their genetic content or they may allude to various conspiracy theories.
“This is an RNA molecule and it does not integrate with your genome. It does not change your genetic material,” says Patel. “If people really want to look for information, they can refer to the Government of Canada, the WHO, the Centres for Disease Control and others. These are the authentic sources with really easy-to-use information. Stay away from conspiracy theories and false information.
“Look for authenticated sources, not blogs written by people who have no idea what they’re talking about. Everybody is pretending to be a virologist and vaccine expert. People should rely on information from medical professionals and follow the government’s recommendations. The politicians also need to listen to their medical professionals. If I have a plumbing problem, I’m not going to ask an electrician to fix it. I need to get a plumber.”
Around the globe, approximately three per cent of people infected with SARS-CoV-2 have died. The encouraging data on the safety and efficacy of mRNA vaccines, where survival is extremely likely, make it a logical alternative. Patel points to the fact that many vaccines, including Hepatitis B, diphtheria-pertussis-tetanus, rotavirus, and measles-mumps-rubella-varicella vaccines, have prevented numerous outbreaks.