Makary: Interesting. You know, I'm really interested in what you said about whether or not the spike protein was the right thing to target in the vaccines -- and it turns out it was very effective. Because I was having this conversation with one of my colleagues who does a lot of immunology research. And I asked the question -- I like to put big questions out there to have a discussion -- and the question was, do you think natural immunity or vaccinated immunity is stronger, and which one's more durable, two different domains. And I'd love your thoughts on that. But one interesting thing he said was he thought that maybe natural immunity, if you really get sick and you've got to mount a big antibody response, may be better because your body is developing antibodies and memory to all of the surface of the virus, not just the spike protein, and that may be better immune protection.
Racaniello: I think it's an interesting question and there's no one answer because every virus is slightly different. For example, the human papillomavirus, the vaccines we have make amazing immunity, better than immunity you get from natural infection, because there's so much protein in those vaccines. And you end up having great mucosal immunity, which is what you need there. On the other hand, other vaccines allow infection without disease. Of course, the polio vaccines were only tested to prevent polio, not to prevent infection. That's all we cared about.
Now for SARS-CoV-2, yes, having other proteins in the mix is a good idea. I think it depends on the severity of the disease. We did a paper 6 months ago which studied people who had died from COVID. So this was a very serious disease. And their lymph nodes had no germinal centers, which means no memory B cells to SARS-CoV-2. Even though they had antibodies, they had very low affinity antibodies.
And so the outcome of that was the idea that if you have a very serious disease, then you're not likely to have a long memory response. Now, those are people who died. So we don't know how it applies to people who have lived because they were able to take out their lymph nodes and study them. And it's not so easy to do in people who have survived. So a natural infection can have consequences. So, on the one hand, yes, you make a lot of viral proteins and those are great epitopes for mainly T cells because I think most of the antibodies that are going to block infection are going to be spike directed. But any other viral protein could in theory be a T-cell target. So you'll get more epitopes.
The counter view is that the virus may encode immune antagonists that could alter the immune response in some way that's not as good as, say, a vaccine. So it really depends. And we don't know enough yet. So I think if people are making a blanket statement that natural infection is always better, that's not always correct. It really depends on the virus.