What are the difficulties/challenges against developing a coronavirus vaccine?

Question

Multiple groups of scientists are trying to develop a coronavirus vaccine but they are not yet being fruitful. What challenges or difficulties are there in the process that slowing down and/or causing failure in development of vaccine?

Answer 1

There are multiple challenges presented, and many of those are not limited to coronavirus vaccine.

As mentioned above, it just takes time. Before a vaccine can be used in patients, clinical trials must be performed to validate the safety and efficiency of the vaccine candidate. A Clinical trial includes three phases, which again, just takes time.

But to really answer your question, what are some challenges of developing a vaccine?

To begin with, from the perspective of lab research, we first need to develop a vaccine candidate. What protein on the virus should we take as an antigen? There are many many proteins on the virus, and for CoV, we know it is a protein called Spike protein. It is the neutralizing target on the virus. Which means, when an antibody bound to this site, it could prevent the virus from infecting the cells. Okay, then we have to know, do we need to do something to this protein to make a vaccine? For example, when we try to manufacture this protein into a vaccine, what if the protein is degraded? Or it somehow becomes a 'bad' protein that simply cannot stimulate immune responses in human? These are just some examples of roadblocks of developing vaccine.

Let's suppose we finally work those out. Then what's next? Each candidate vaccine needs to be tested in animals before going into human clinical trial. This step is time-consuming.

Now we are finally ready to start clinical trials. According to FDA, the vaccine for human trials (also for each drug) needs to be produced under Good Manufacturing Practices (GMP). It's basically a standard operating procedure to make sure that the vaccine candidate can be manufactured in a large-scale, quality-controlled manner. There are many many challenges, like how to purify the protein? How to scale-up production. This is partly of the reason why the first vaccine in trial in USA is an mRNA, and in China is a DNA, both of which does not require complicated protein purification.

As you can see, the list of challenges can go on and on. But there are scientists and doctors working diligently on it. Hopefully we'll get there.

Answer 2

Vaccine development is not as easy as just inject some inactivated virus as:

1. Vaccine can have side effects such as inflammatory reactions. So for a good vaccine the side effects must be negligible or within a tolerable limit.

2. Vaccine may not induce immune response. It may be ignored by the immune system as just some random debris. So a good vaccine must be recognised as a foreign object by the immune system.

3. The vaccine may be not so specific. I.e, the immune response may have high cross-reactivity that may undesirably interfere with some undesired biomolecule or unrelated process.

4. The desired activity of the vaccine may be too specific, i. e. on slightest genestic variation of the virus, the vaccine may fail.

5. An attenuated strain as a vaccine, may have a possibility to revive and form revertant strains. A good vaccine must be safe from pathogenicity

6. The immune response may not last long. For a good vaccine the immunity have to last long.

7. The shelfed vaccine must have some stability with time, temperature, transport etc. If the vaccine quickly loses its activity then it wont stay usable.

8. Some individuals may not respond to the vaccine, such as depending upon genetic preconditions. So a good vaccine must elicit immune response to a wider range of population.

9. There may be challenges regarding isolation, preservation and maintaining a desired 3-D structure of the protein from virus.

Alongwith

10. Any research-process tend to be slow, and unpredicted problems may appear at any steps.

These are likely to make any vaccine development as conceptually slow, tedious, testing dependent, and safety concerned.

References:

Polio vaccination: Past, present and future

The ideal vaccine

Eliminating vaccine cross-reactivity

Vaccine efficacy article on Wikipedia

Answer 3

Immunology is very complex, with so many interactions that prediction is difficult.

For example, some vaccine candidates will probably be designed to provoke an immune response against the proteins on the spikes of the virus. If that protein is similar to proteins already existing naturally in the body, then the vaccine wont work, because immune cells that attack the self are destroyed during their maturation.

Answer 4

A vaccine needs to be able to neutralize the virus (bind to it and masking from entering the cell) with high affinity. Now the virus is a large complex structure, so it is not immediately clear how to design a vaccine that can achieve that.

Screening antibodies from recovered patients might be a good idea, but it takes effort and time. What is more, the antibodies isolated from those patients may not be optimal for a vaccine, and some rational design based on those antibodies might be needed.

Another challenge is how to get a sustained level of vaccine proteins in the human body. The cutting-edge in the field right now is to use mRNA instead of proteins. You can read something about Moderna, which spearheaded this effort in the pandemic. But we still do not know what those RNAs are doing and where they are going in the body, so it takes many experiments and creativity to send those mRNAs into the human body so it can function properly.

To make a vaccine, you also need very strict production standard known GMP to make sure that the product is clean, pure and safe. This is not very easy and not every lab in the world can do.