As a a virologist, I’m reassured by data out of China showing that a fairly basic vaccine protected monkeys from SARS2 #COVID19-like disease. While this was likely result, details are important- they didn’t see “enhancement”, which many feared. biorxiv.org/content/10.110…
This vaccine is made by growing SARS2 in cells in a laboratory and inactivating them using a chemical that basically freezes the virus. If the virus were the Terminator, it’s like you’ve soldered the robot’s joints in place… it’s renders the bad guy harmless but still…
…lets immune system study what the bad guy looks like so it can prepare to spot the invading army of Terminators (aka immunity). I’ve discussed how immunity works in other threads – look at my pinned tweet. (Please do look there first b/f asking questions- faster for you.)
Note: Flu vaccines are made same way: grow strains of flu (in chicken eggs) & inactivate resulting virus. Importantly, this group mixed their inactivated SARS2 w/ an immune stimulant (adjuvant) called Alum, which puts a spotlight on the vaccine, drawing immune system’s attention.
That Alum was used and vaccine was effective is reassuring b/c cutting edge vaccines have moved on to other, in some ways better, adjuvants. Indeed, other adjuvants should be better. But so far it's good to see that Alum could be good enough. So here's what the researchers saw.
When monkeys (specifically, a species called rhesus macaques) were vaccinated with various doses of the inactivated SARS2 vaccine, the monkeys developed antibodies. When the monkeys were then exposed to SARS2, the animals were protected from disease.
The high dose of the vaccine protected animals so well that researchers saw little signs of virus even replicating after animals were exposed. That's good. If virus indeed was blocked from even infecting, then it means that a vaccinated person, if exposed...
...might not become a carrier (i.e. might not spread infection). The middle and low doses of vaccine allowed the monkeys to become infected (so they could likely still spread it) but …their lungs were protected from infection and they showed no or few signs of disease.
Unvaccinated animals became infected and showed clear signs of disease. The vaccine worked. And if we had a vaccine that worked anything like this and everyone took it, we would likely achieve herd immunity & save millions of lives without the need for further social distancing.
This was always the most likely outcome of such a study – we know how to make vaccines. But there was also a risk that maybe some vaccines, particularly crude ones like this Alum-adjuvanted inactivated virus vaccine, would cause disease enhancement (i.e. make an infection worse).
That was seen once with an RSV vaccine in the 1960s. And having antibodies after one's first infection by Dengue virus can make second infection with a related strain worse. That's thought to be b/c sometimes antibodies can help virus infect cells it otherwise couldn’t infect.
If you’ve read my explanation of antibodies as being like police dogs that grab onto part of a bad guy (see pinned thread), then antibody-dogs are most effective when they grab a part of bad guy that stops (neutralizes) the bad guy from breaking into a home (infecting cells)...
...or attacking a police officer (immune cell). But imagine that a police dog grabs a criminal by the pant leg, slowing him but leaving him free to turn on the police officers drawn to the skirmish. That can happen and cause virus to be more likely to infect immune cells...
...which can make the disease worse. That happened in case of SARS1. A vaccine that introduced just a part of SARS1 (vaccinia vector encoding full-length spike protein) into rhesus macaque monkey was successful in generating...
...antibodies, even some neutralizing ones, but, when monkeys were infected w/SARS1, their disease was worse than the disease SARS1 caused in unvaccinated animals. This paper has remained in the back of my mind, worrying me just a bit. Now I feel better. insight.jci.org/articles/view/…
The other vaccines in development are in some ways likely to be better than this inactivated viral vaccine. They use modern adjuvants that tell the immune system to make the right kind of antibodies (for scientists: TH1-skewing towards IgG1) instead of wrong ones (IgG4).
Admittedly, the vaccine that showed SARS1 enhancement was a somewhat more modern vaccine that should have made the right kind of antibodies & yet it still showed enhancement, so we need more animal data. Fortunately...
...all the companies working on vaccines are working with various laboratories around the world on these kinds of animal vaccination and infection models (called “challenge” studies b/c animals are “challenged” with virus). It’s good to know that, even if some show enhancement…
…we now have at least one type of vaccine in development that works in monkeys and doesn’t cause enhancement. Note: a vaccine research unit at Colorado State University is also working on a SARS2 inactivated vaccine (@BARDA- please take note). source.colostate.edu/researchers-se…
Bottom line, as I’ve written before, vaccines are coming and they will work. I estimate that we should have vaccines available for healthcare and other front-line workers towards end of this year and for masses sometime in March/April 2021. Until then, stay safe.
By the way, for those who will rightfully ask what would make me feel even more comfortable that a vaccine won't cause enhancement, it would be seeing that labs can actually cause enhancement of SARS2 with some intentionally bad vaccine.
That animal work is ongoing. Would reassure us that enhancement is possible but that vaccines we are taking into human trials aren't causing it. Also, actual human data will help. Those studies are also ongoing; I would expect first data from a large enough study in June/July.
