Vaccine Challenges
By Nayyer Ali MD
The world continues to groan under the burden of the COVID-19 epidemic. While case rates and fatalities are under control in East Asia, they continue to explode in Europe and the US. Third World countries are also seeing disease spread and economies shudder to a halt, but with less robust public health systems, it is hard to get a sense of how bad the disease is afflicting them.
Even with the relative success of East Asia, social distancing and reduced economic activity continue to keep the virus from surging back into epidemic spread.
Bill Gates correctly remarked that the world is not going back to normal till we have a vaccine. This is absolutely true. But what are barriers to getting a vaccine and how soon can we expect one?
The basics of vaccination are well known. If your immune system encounters a new virus, it recognizes it as foreign and develops special proteins called antibodies that specifically bind and kill the virus. We can jumpstart this process by exposing a well person to a part of virus or a dead or weakened virus to induce this response without causing the disease. This works for most viruses with a few exceptions. If the virus has a very high rate of mutation, then it changes its outer coat so often that one infection does not prevent you from getting or another next year with a mutated version. This is why a flu vaccine is given every year. HIV, the virus that causes AIDS, has several complex mechanisms that allow it to evade our immune response. But most viruses do not, which is why we can vaccinate for smallpox or measles or yellow fever.
There are over 50 groups working on developing a vaccine, and two have even dosed their first human subject in early trials. So why is this going to take a year or more? The process is lengthy because we need to make sure the vaccine works and that it is safe. First, a candidate vaccine needs to be designed. There are many different approaches being taken, from very traditional to a brand new strategy that has never been tried with any previous vaccine. The vaccines will need to be tested first on monkeys, both to see that it is safe in them, and that it induces them to make antibodies to the virus and protects them from infection. Once that is done, human testing can begin. The first round of testing will be for safety, with volunteer test subjects getting the trial vaccine and being observed for any side effects or complications. This will take two months at least to accomplish.
The second round of testing will be to find out if the vaccine induces the production of useful and persistent antibodies. The proper dose to get this response will need to be determined. The antibodies produced will need to be analyzed for their ability to destroy COVID-19.
The final round is testing for efficacy. This can be a lengthy process. To find out if a vaccine works, it must be randomly administered to a group of subjects, and not given to another group. The two groups then must be tracked closely to see how many patients get infected over the next several months. In the case of vaccines for HIV or malaria, these groups must be tracked for years. What you need to show is that the group that received the vaccine had much fewer or perhaps no cases of the disease than the group that did not get the vaccine. The results must be so striking as to leave no room for doubt that the vaccine works. This final round could take six months or more, depending on how many infections are seen in the two groups and how much virus is circulating in the community.
Can this key step be sped up? Yes, it can. Normally in a vaccine trial, the researcher does not intentionally try to infect the test subjects with disease. It is left to chance and time to see if infections occur. This is only ethical, one does not intentionally try to sicken people in the name of science. But given how profoundly destructive this virus is to the global economy and to the rhythm of our lives, could we make an exception here? For example, instead of having a few thousand test subjects get the vaccine and a few thousand control subjects not get it, maybe we give the vaccine to a few thousand people, then challenge them with the virus itself to see if they do not get infected? If they do not, it would prove the vaccine works and we could answer the question in less than eight weeks rather than six months or more. But how could we ethically do this? Such an approach requires intelligent well-informed volunteers who understand the risk. They could be compensated, but we do not want to distort people’s choices too much by money. We would use only young healthy people, who do not have much risk of dying from the virus. But we still need a backup plan in case a subject became seriously ill if the vaccine didn’t work. One option is to be prepared to treat these patients with transfusion of serum from a donor who has recovered from COVID-19. A recovered patient is making antibody to the virus, and we could use their serum as way to transfer those antibodies to an infected individual. This plasma donation therapy is already being tried and initial reports are positive. If this does in fact work, then we would have the ability to rescue a vaccine subject who gets the infection. If an effective anti-viral drug becomes available that too could make it safe to do this sort of accelerated vaccine study.
We need a vaccine to get back to normal across the globe. Developing one as quickly as possible is a priority. We should look at deliberately challenging test subjects with the virus as a way to rapidly determine if an experimental vaccine will actually work.
