Why can’t we have a vaccine for coronavirus tomorrow?

As the acute phase of the novel coronavirus pandemics starts to ebb, the discussion is moving towards vaccines and how can we protect the populace from another wave in the fall or the next spring

It seems clear that to fight off the virus, and prevent another public health crisis, most if not all of us must have immunity (herd immunity).We will develop the immunity either by having been infected and recovered, or by having received a vaccine.  This reality is the force behind the rush to develop a vaccine sooner than later.

Whereas you, I and our elected officials would like to have an effective vaccine available for everyone who wants it, tomorrow, it just cannot happen that fast. For an effective, safe, commercially available vaccine in hundreds of millions of doses (or billions of doses for the whole world), there are many known and un-foreseen challenges.

I have discussed the basics about vaccines in a previous blog and will skip them here.

One of the challenges is to determine what component of the virus should be used for the vaccine. Do we use the whole virus, some of its parts, its spikes or it’s RNA (the innards)?  No one knows that for sure. The scientists cannot use the whole live virus, as it will cause infection. So can they use a dead virus, partially dead (attenuated) virus, or perhaps a piece of it? If so, then which piece that will serve as the best stimulant (vaccine) to yield effective antibody for protection against the viral infection?

At this given moment, many companies, private and not-for-profit, universities and the governmental institutes are working on all of these issues all over the world. Each step requires its own time to be accomplished.  First, different components (potential candidates to be vaccines) from the virus must be isolated, purified and injected in different laboratory animals to find out which one elicits the best immune response. Choosing the right laboratory animal is also important because the immune response of each animal may be different. After injecting the viral component, one must wait for the animal to develop antibodies. Once there are enough antibodies, they are extracted from the blood of the animals and tested against the virus. This helps pick the best component as the potential vaccine.

If the animal experiments, also called the pre-clinical studies positive, the researchers then the permission to move on to human clinical trials. The human trials are usually held in three phases. Phase I involves only a handful of human volunteers. The purpose of phase I is to find how does the human body reacts to the potential vaccine or chemical and what is the maximum tolerable dose. Once successful, the phase II is initiated. Phase II needs a larger group to assess the safety and efficacy of the potential vaccine or a drug. This is followed by phase III trial where hundreds or thousands of actual patients are enrolled. The phase II and phase III trials can be open or blinded ( where the patient and the doctors either know or don’t know what is being given), non-randomized or randomized (where the researchers pick or chose the recipient vs a computer automatically assigns the treatment respectively) and whether the research item is being compared to a placebo or an already known treatment or vaccine. Hence the designs of various randomized clinical trials (RCTs) can vary one from another.

It is challenging to find volunteers who agree to be guinea pigs even if they are paid to participate in such a research. For the trial to be statistically valid, one needs to have a certain number of participants in a trial. Will the researchers be able to get all the participants that they need? If many trials have been opened at the same time, will it make it even more difficult for each to enroll the required number of participants?

The other hurdle is this: Will the participating patients be willing to accept a placebo rather than the real vaccine as a requirement of a phase III trial ?  Of hundreds of people who are interviewed, only a few agree. 

Given the fear and uncertainty about this virus and some of the challenged listed above, it may take a long time to enroll enough participants to get the trial off the ground.

What if by time the trials are completed; the infection has already started to wane or even disappear? Will the private companies be willing to invest in manufacturing a product at a great cost, knowing very well that their product may no longer be needed?

It takes many months or years to design, plan, recruit patients, conduct the trial, collect, and analyze the data and present it to the FDA. We only have one FDA and hence everyone must get in line for their turn to be able to have their projects evaluated. Many a times, after the initial review, the experts at the FDA may send the researchers back to the bench for correcting the statistical analysis or clarifying the data.

Another important aspect of developing a vaccine is funding. It takes millions or even billions of dollars to carry out the research, manufacture, store, market, distribute, and sell a new drug.  As a business, it makes sense to invest the dollars to invent a drug and if successful own its patent and reap the profits for many years to come. Vaccines on the other hand do not have a long shelf life. The viruses change and mutate, and new ones arrive ever year, making the previously manufactured vaccines ineffective. That is one reason most vaccine are produced with public private partnerships.

If a government invests in developing a vaccine, should it limit its availability only to its own citizens? In a world today, travel is cheap and easy, and people are constantly moving taking the viruses with them from place to place. Should the production of a vaccine against a pandemic like this one be a joint global effort, and if so, how do we assign financial burden on various nations? If a vaccine is successfully developed by a commercial entity, how should it be priced given the disparities and purchasing power between the developed and underdeveloped nations? How much profit should be allowed the private entrepreneurs and companies who put up the money for developing the vaccine? These are difficult questions and can only be answered by collaboration.

Lets us hope that with enthusiasm, creativity and collaboration, we can help us overcome these hurdles and have an effective vaccine available “very soon”.