It seems likely that the only way we will be able to go out of our homes and relate to the rest of society in a “normal” fashion is to have an effective vaccine. At least for the immediate future. Once more than 60% of the population is immune, or has been immunized, the concept of “herd immunity” takes over. At that point, casual interaction with a stranger is much less likely to lead to disease.
Vaccine manufacturing and marketing is tricky. For some diseases, antibody production does not lead to a cure. For example, HIV antibodies do not protect people against AIDS. The HIV virus has found ways to avoid being attacked by antibodies. Many people with hepatitis C suffer devastating complications from this virus despite their having plenty of antibody. This is one of the reasons that the search for an AIDS vaccine has failed (so far) to produce impressive results.
Vaccine makers look for what they call a “target.” In the old days, whole viruses, made weak by chemical treatments, were used as targets. This technique is still used for many vaccines. Today, most of the time the target is part of one of the proteins that surrounds the virus. Since viruses mutate so often, the targeted protein should be one that has shown the least tendency to mutate. When a virus changes its protein coating, there is only so much tinkering that it can do. A drastic change in the core of the protein molecule would change its shape in a way that it would not fit well around the viral genetic material, thus leaving it exposed and defenseless. Most COVID anti-protein vaccines are focusing on its “spike” protein; the small protrusions that you see in the ubiquitous COVID diagrams. So far, the spike protein has not shown a strong tendency to mutate, which probably means that any significant change in its composition has led it to collapse on itself, as egg proteins do when you heat them.
Anti-protein vaccines are made by breaking up the protein into smaller pieces, then trying to figure out which piece is more likely to elicit a strong antibody response. Sometimes the whole protein is used. This explains why there could be dozens of different vaccines that are supposed to do the same thing: attack a certain protein.
Another way to generate a target protein is to use the virus genetic material to teach our own cells how to make a viral protein. These are called RNA vaccines. A (courageous) healthy volunteer is injected with viral RNA. The volunteer’s cells make whatever viral protein the injected RNA codes for. The volunteer’s immune cells recognize that this protein does not belong to the volunteer. Lots of anti-protein, therefore anti-viral antibodies are made.
RNA vaccines have the advantage of convenience. We will not have to build huge incubators that will grow enough virus for us to split into little pieces. Viral RNA can be snipped from only one virus, placed into a yeast (or many other types) of cell, and millions of RNA copies come out quickly. The disadvantage is that this a new concept: we do not know if it will work. The first human volunteer was injected with Covid RNA in England a couple of days ago.
Another theoretical target is the receptor, or anchor, that the virus uses to hook itself onto the cell. It could be blocked in some way that will not be harmful. There are people who have a genetic mutation that lacks the receptor that HIV needs to get into our immune cells. These people never get sick if they are exposed to HIV. I know a lot less about these efforts, but they are promising.
Once clinical tests are started, information must be gathered. Is there an age group, or racial group, that fails to make adequate antibodies? Are coexisting conditions a barrier to generate protection? Are they safe to use in people who are immunosuppressed? There are instances (uncommon, thankfully) where people who have been vaccinated get sicker than “normal” when exposed to the targeted virus. Will this happen?
Of course, the most important information gathered is about efficacy. Are the antibodies that the vaccine induces capable of killing the virus? Are enough of them generated? Will they last for a year, or a lifetime?
Massive data collection about safety is essential. A 1% rate of serious side effects is unacceptable when the goal is to vaccinate billions of human beings. Therefore, any vaccine made is unlikely to come to market sooner than 18 months away.
Treatment is also complicated. The potential targets are numerous.
Receptor blockers. Inhibitors of RNA production. Compounds that force viral proteins to twist in a way that renders them useless. Fortunately, there is a data base of thousands of chemicals that have been made to do one of the things discussed above but were not used because better options were found. At least 400 chemicals are being considered and tested.
You have heard about hydroxychloroquine, which is being looked at, and remdesivir, which has been tried in several hundred people. There is much more to come. The problem here is that each drug company has been very jealous about keeping a lid on their product. I have no problem with the pursuit of profit, but maybe there is a role for a higher authority to order all of them to cooperate, with a guarantee for reasonable profit for the makers of the best products.
Where do we go from here?
As I said yesterday, the logical next step is for every nation, every manufacturer, and every scientist to come together and exchange ideas and chores through a common platform. Yesterday the WHO announced the beginning of such a group. So far Germany, France, Burroughs, and other firms have agreed to participate. The Saudis have donated $2 billion, and Bill Gates has also given money. They need $8 billion to start; a mere pittance when we consider what this virus has and will cost us. The United States and China were nowhere to be seen at this announcement.
One wonders: To what extent will national pride prevent us from being one of many to get the credit? Can we, just for this quest, settle for being great instead of the greatest?
This Post Has 11 Comments
This explanation is an excellent introduction to a very important process against which to measure the numerous expectations that are being bandied about in the myriad news items broadcast, printed and retold each day with varying degrees of accuracy. Thank you!
Thank you; it is very difficult to read between the lines of what we are fed. Just yesterday, Dr. Hahn of the FDA danced around a question of whether the POC antibody tests available were accurate. From my reading, and from the infectious disease specialists that I know, the answer is a resounding NO; accuracy is as low as 20%. He did not acknowledge this. In the meantime, people are dying and the survivors are scared.
It’s important to keep well informed on this, literally as if our lives depended on it, which happens to be the case.
My head is spinning after this one, but always impressed with your knowledge and ability to try to help us all understand
Thank you for explaining this very complicated process of trying to develop a vaccine. I very much miss your knowledge of treating my own RA. Having had RA for 54 years, should I be worried about getting this virus when businesses start to open again? Should I continue to stay out of the public. Would like your opinion.
Yes; you are at risk, both because we are getting older and because your immune system is malfunctioning for quite a while. I wish that I could be more optimistic; I’m afraid we have another year of distancing ahead of us, with a few lulls here and there. A WHO warning from today says that even having antibodies against COVID may not protect you from getting sick (as happens with HIV). Life has changed.
Thank you Dr. Garriga – my old Paco friend! Dear Kathy Noelker sent me these four posts and what a wealth of information!! I would so enjoy your future posts! Sending good health vibes to you and Phyllis!!
Love to be back in touch with the sisterhood.
Thank you for all this information. It is a whole lot for me to take in but I get the idea that this will take a while.
Nice to see you active on your blog again Dr. Garriga! Thanks for the very thorough explanations that are helpful to understanding all that is happening right now. Stay healthy!
Thanks for the encouragement. Hope to be able to circulate again by summer’s end.