COVID-19 cases are on the rise across the country, and the public is eagerly anticipating the development of a coronavirus vaccine. But most people are not vaccine experts, and questions often float around the internet, inciting uncertainty and confusion. Luckily, WWU has its very own virologist; to find some answers, Western Today chatted with Associate Professor of Chemistry Gerry Prody.
Western Today: What is a vaccine?
A vaccine is a way to stimulate your immune system to start to mount a response to something that you might encounter in the future. In other words, it’s a way for us to develop immunity to a pathogen before we actually get infected by that pathogen and so we can develop immunity without getting sick. Considering an antiviral vaccine, one often targets the outside of the virus, or the coat protein as the vaccine agent. This the case for several of the promising vaccines in development against SARS-CoV-2.
Western Today: How do they work?
There are 4 types of vaccines; each have slightly different modes of action.
1. Live-attenuated vaccines: This form of vaccine contains weakened strains of the pathogen so it is capable of replicating in our bodies. It will generally produce a very robust and long-lasting immune response, stimulating both the humoral arm of the immune system to produce antibodies and the cell mediated arm of the immune system to produce specific T cells, although people occasionally come down with a mild form of the disease from this type of vaccine. These vaccines also must be kept cool to remain viable. The MMR (measles, mumps, rubella) vaccine is one of these, for example.
2. Inactivated vaccines: As this name implies, this type of vaccine contains “killed” versions of the pathogen. The immune responses to these vaccines are not as strong or long-lasting as the response to live vaccines. Rabies, polio and flu are examples of this type of vaccine.
3. Subunit, recombinant, polysaccharide, and conjugate vaccines: This type of vaccine relies on a small piece of the pathogen to stimulate an immune response. In the case of some of the COVID vaccines under development, the S or spike protein of the viral shell is the vaccine target. The idea is to have the immune system recognize the virus shell, and produce antibodies against it without coming in contact with the virus itself. Some examples of this type of vaccine are the shingles vaccine, the HPV (human papilloma virus) vaccine, and the Hepatitis B vaccine. An emerging problem with this strategy may be that people who are recovering from COVID-19 infections do not seem to retain their immune memories for very long—just a few months. So even if these vaccines work, we may need to be revaccinated frequently.
4. Toxoid vaccines: Some pathogens, especially bacteria, produce toxins which are actually the disease causing agents. Vaccines can help protect against these toxins. Examples of this type of vaccine are the tetanus and diphtheria vaccines. These, as you know, require booster shots over your lifetime.
Adding to these possibilities are the use of molecular biological tools to enhance our abilities to create vaccines without relying on the pathogens at all. Recombinant DNA technology exploits the DNA or RNA sequences that encode for the proteins to be expressed once they have been administered. One of the promising COVID vaccines under development is an engineered RNA vector which codes for the spike protein mentioned above.
Western Today: What does it take to develop a vaccine?
Vaccine development, in general, is a long and arduous process, as well as an expensive one. Once people identify a disease to target, they need to define strategies to stimulate the immune system to fight it, and the immune system is an incredibly complicated beast.
Once the strategy has been locked down, usually university or pharmaceutical investigators develop a potential vaccine or vaccines, and then animal testing begins to see if the vaccine is safe in animal models and if an immune response is generated. Then, further testing ensues to see if that immune response is protective. If all those results are positive, clinical trials may be initiated. The FDA sets the rules for these next sets of tests. In Phase I, between 20 and 100 healthy volunteers are tested to see if the vaccine is safe: are there any serious side effects? Does the dose affect the side effects? etc. This usually takes three to six months, and then a few more months to process the data. Then, in Phase II, there are several hundred volunteers receiving the vaccine. They are checked for the most common side effects as well as their immune responses. Again, this takes months or more with additional months for data crunching. Finally, if the preceding tests indicate that the vaccine is safe and efficacious, some might receive approval to move to Phase III clinical testing involving thousands of volunteers. This usually involves a longer period of time, often 18 months to 2 years, with more time for analyses.
Only about 10% of drugs/vaccines that enter clinical trials ultimately receive FDA approval. And then, the scale up to the manufacturing of millions of doses of the vaccine has to occur. This timeline usually takes about 10 years.
Western Today: There are many false statements and myths surrounding vaccinations (i.e. they have toxic substances in them, they cause autism, etc.). Can you debunk these for us?
In general, vaccines are very safe and save lives. One has only to look back at epidemics like the polio epidemic in the 1940s and be thankful that we have been able to control that illness and many others in America thanks to vaccination. Vaccines contain many ingredients, due to their nature. They need to be manufactured in bulk, stored, shipped, and remain stable for periods of time, etc. Among other things, vaccines contain adjuvants which stimulate the immune system’s response to the vaccine. In the lab, these could be things like mineral oil. In manufactured vaccines, the commercial adjuvants used are similar to those found in antacids, antiperspirants and other common items.
Vaccines also contain small amounts of formaldehyde to prevent bacterial contamination during manufacturing and distribution. This is a normal body chemical, also found in the environment and many household products. The main ingredient accused of causing autism was Thimerosal. This hypothesis has been totally debunked and the person responsible for propagating it, Bryan Wakefield, a British physician, had his paper describing the purported link to autism retracted and his medical license revoked. Since then, innumerable studies have found no links whatsoever between Thimerosal and autism. Regardless, no vaccines available now contain this antibiotic with the exception of the multidose flu vaccine, and single dose vaccines are available without Thimerosal.
People can develop mild symptoms from vaccines, as one can from any medication. Severe reactions are rare, although not nonexistent. Certainly, it is far, far better to do preventative treatment, i.e. vaccinate, than to try to treat the potentially fatal diseases once they develop. Vaccines also help populations develop immunity and that is the only way society will be able to win the fight against a pandemic such as we are facing now.
I grew up in a time before vaccinations were available. I did receive the polio vaccinations as a child (on a sugar cube) and I am probably among the few reading this who was vaccinated against smallpox, a disease with no known natural occurrences today (Hopefully, it will not rear its ugly head now that corpses are melting in the tundra in Siberia, where many smallpox victims were buried during the last epidemic.). When I was a child, if another child came down with mumps, measles, or chicken pox, the child’s mother would call all our mothers to schedule an impromptu “party” so that we could all become infected as youngsters rather than run the risk of developing more serious illnesses later in life.
Trust me. Vaccinations are better.
Western Today: Based on what you know, when do you predict a COVID-19 vaccine will be developed and widely accessible? Have you heard anything about the timeline?
At this time, there are upwards of 150 vaccines under development around the world, with 27 in human clinical trials and a handful of those looking quite promising. In fact, just this week, the Oxford group in England announced that they may have a vaccine available to go to manufacturing by September! They are making the risky decision to start gearing up manufacture even as the vaccine just enters Phase III trials. The vaccine should be available for frontline workers almost immediately after completion of Phase III trials. Our current administration has invested billions of dollars in several different groups that are fairly far along in the vaccine development. Whether or not any of these vaccines will actually come to fruition is anyone’s guess. The Oxford vaccine, which is called ChAdOx1 nCoV-19, is undergoing large scale trials in Britain, Brazil and South Africa. It is made from a non-replicating version of an adenovirus, which is one of the viruses that causes the common cold, and it expresses the part of the coronavirus spike protein. This protein is what binds to receptors (ACE-2 or angiotensin I converting enzyme 2) on our cells to gain entry.
Scaling up manufacturing takes time. If we have widely available vaccinations within a year, I would call that pretty amazing. Dr. Anthony Fauci, our chief scientist on infectious diseases, is predicting 12-18 months.
The next problem seems to be allocation of the doses once all the manufacturing hurdles are overcome. No one seems to know who is in charge of this. Under normal circumstances, this should fall under the auspices of the CDC, but they have been particularly silent (or silenced?) Someone needs to decide the order of allocation of doses when and if manufacturing starts to ramp up. We can probably all agree that front-line hospital workers should get the first doses, but what should happen after that?
Western Today: There are rumors that the COVID-19 vaccine is being rushed through the development process and people are concerned that this will make it unsafe. What are your thoughts?
This is not a rumor. These vaccines are being pushed through the pipelines at pandemic speeds never before attempted nor realized. As I mentioned earlier, the Oxford group’s vaccine may be ready for emergency use by September. That is unprecedented. Normally, Phase III clinical trials last 12-18 months alone so that safety and efficacy issues can be thoroughly addressed and analyzed. Obviously, shortcuts are being taken in the interest of global health. The FDA will likely also shorten the approval processes. Will the risks be worth it? We can only wait and see. And hope. The good news is that these vaccines relied heavily on previous research done on the related viruses of SARS and MERS so that the preliminary research steps that usually take 2-5 years were previously completed.
Of the vaccines in the clinical trial stages, several invoke novel vaccine strategies that have never been used in humans before. They will undergo the full spectrum of safety and efficacy tests. Also, before their use is put into practice, many additional obstacles such as the need for very specialized distribution systems will need to be addressed.
Western Today: Another concern surrounding the COVID-19 vaccine is that this virus mutates too quickly and the vaccine won’t be effective on mutations. Do mutations often cause issues with vaccines? Based on your expertise, do you expect mutations to cause issues with this vaccine?
This does not seem to be a big problem for this virus. Unlike most RNA viruses, it is able to find mistakes and correct them. This is due to a proofreading function called ExoN which most other coronaviruses don’t have. This domain is part of the RNA polymerase which replicates the viral RNA. When it detects a mismatch, which would normally lead to a mutation, it fixes it. Because of this, the Sars-CoV-2 mutation rate is much lower than most other RNA viruses like HIV or influenza.
Infuenza has an additional challenge because it can undergo recombination with other forms of flu. It’s difficult to predict which combination we’ll see in a given year, which is why we need to have new vaccines each year. With Sars-CoV-2, we have the lower mutation rate working in our favor with respect to developing a stable vaccine. It is hoped that even if the virus does mutate, there will be sufficient similarity to the strain used in vaccine development that vaccination may reduce disease severity, even if it does not provide complete protection from infection.
Gerry Prody has taught at Western since 1984. She received her doctorate in biochemistry from the University of California at Davis in 1981. To read our last Q&A with Prody about what viruses are, and how they work, click here.