Archive for July 23, 2020

On the Many Potential Real-Life Problems with Any COVID-19 Vaccine

July 23, 2020 26 comments

Most of you might have recently heard something about progress in the development of one (or more) of the many vaccines being developed for COVID-19. While I don’t want into a lot of detail about the types of vaccines being developed, two are getting most of the attention. One is the ‘RNA-based’ one such as those from (Moderna, Pfizer etc. The other type is adenovirus-based ones such as that Oxford-AZ and CanSino vaccine. Even with the initial results of these, and many more, vaccines- I predict that even the most successful vaccine will have to overcome tons of real-life problems. And I am not the only one to hold that opinion. Here is why..

1] RNA-based vaccines of the type developed by Moderna and Pfizer/BioNTech are problematic for more than one reason. Firstly, no RNA-based vaccine has yet been approved for human or animal use. Sure.. this is partly due to the reason that the technology, injecting encapsulated mRNA to make you own cells produce the antigen you want to stimulate an immune response against is fairly new technology. But there is a second reason- specifically, mRNA based vaccines are notorious for causing grade 3 and higher reactions in a small percentage of individuals. Though Moderna is trying its best to obscure the data, more than a few people in their relatively small phase I trial developed reactions serious enough to require prompt medical attention.

Why does this matter? Well.. let us consider how things will play out if they have a 5% incidence of such reactions during a mass vaccination drive against COVID-19. Imagine you vaccinate a million people and 5% of them develop such reactions. Even if they are can be easily treated in the hospital or a clinic, you have 50,000 fairly ill people who wouldn’t be there if they had not taken this vaccine. Also, if there are 50,000 people ill enough to require medical attention, you can bet a few of them will end up becoming much more ill or even dying. Let me remind you that the mortality due to COID-19 in people under 50 is less than 1 in 1,000. What are the chances that the vaccine kills and hospitalizes as many people as the infection in younger age groups?

This is not to say that vaccines with such high rates of side-effects are useless. The vaccine for smallpox and older versions of the rabies vaccine also had rather high rates of side effects. But there is the thing.. smallpox, when it existed, was a very contagious illness with 30% mortality rate. Rabies has a mortality of almost 100% once the infection has reached the central nervous system. Most people will be fine with a vaccine for smallpox or rabies that kills one in a few thousand people, because of the high fatality rates of those infections. The same cannot be said about COVID-19. To make matters more interesting, we don’t know if mRNA based vaccines are more likely to induce auto-immune diseases than other, more conventional, vaccines.

2] The other main type of COVID-19 vaccines use fairly harmless adenoviral vectors that express some proteins from the virus in question. In contrast to mRNA based vaccines, we have a decent amount of experience with such vaccines in both animals and humans trials. Also vaccines that use a similar strategy- where one fairly harmless virus expresses proteins of a far more harmful virus to induce immunity to later have been used to develop a few vaccines used in animals and at least one for humans (Ebola vaccine). We can, therefore, be a bit more certain that the safety of vaccines in this category is not as unknown as those mRNA-based vaccines. Also, the rate of complications for such viral-vector based vaccines is noticeably lower than mRNA vaccines.

The initial data from the Oxford-AZ vaccine trials also suggest that they do a much better job at stimulating immunity to the virus among CD4 and CD8 T-lymphocytes. It is known that immunity to Coronaviruses in animals is more cell-based than antibody based. In other words, the Oxford-AZ vaccine is likely to produce better immunity under real-life conditions with noticeably fewer side-effects than mRNA based vaccines. The CanSino vaccine, which uses a human adenoviral vector, seems to be a bit less effective than the Oxford-AZ vaccine which uses a chimpanzee adenoviral vector- perhaps, because of pre-existing immunity to human adenoviruses. Between mRNA and adenoviral-vector based vaccines, I would put my money on the later.

3] The next issue concerning COVID-19 vaccination comes down to the logistics of producing, distributing and actually giving the vaccine. Having the best vaccine means shit all if you cannot produce it on a large scale without breakdowns in quality control. Once again, the adenoviral-vector based vaccines are a bit better than mRNA-based ones in that regard, especially with existing infrastructure. Distributing the vaccine, even if effective will however pose quite a few problems. For starters, who do you vaccinate first- the groups most likely to die from infection or those most likely to transmit it? How do you vaccinate hundreds of millions in a very short time without a huge number of people ending up in hospitals due to side-effects, even if temporary.

And what are you going to do about all the people who would rather wait and see what happens to initial bunch of vaccine recipients? What if there is a large wave of hospitalizations from first widespread use of whichever COVID-19 vaccine ends up being approved. Remember even a 2% incidence of severe reactions is a large number once you are talking about millions of recipients. How will you convince people to keep getting vaccinated if initial use of COVID-19 vaccine causes tens of thousands of hospitalizations? This is especially likely for mRNA-based vaccine such as those being developed by Moderna and Pfizer/BioNTech. Then there are issues of efficacy. What if the approved vaccines prove to be only 80-90% effective. While this is a perfectly acceptable for many existing vaccines- dumbfuck “ivy-league experts” have promised the sky to masses.

I can think of many other issues, but we are already past a thousand words. Might write more in a future post on this topic, depending on responses to this one.

What do you think? Comments?