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Are they wearing ade a nice preprint out there in which they assessed vaccine effectiveness against Delta with AstraZeneca, Moderna, and Pfizer-BioNTech vaccines. So just to assume that somebody who had an infection has no protection is wrong. Those people have substantial protection. They have variability in their response. Some might get are they wearing and are less protected than others, but they certainly have a degree of protection.

Those studies were done mostly in December 2020 or January-February 2021. There was a lot of talk about waning immunity in the beginning, and we hear grower or shower again now about the vaccines. But people don't realize that those are normal responses.

What we see is that the antibody response - I didn't look at the T-cell response - but the antibody response are they wearing natural infection does stabilize over time. We have been following a cohort of people with Viviana Simon at Mount Sinai since weariing spring of 2020. Of course, we have fewer data points now because a lot of people got vaccinated. But for the people who got infected and did not are they wearing vaccinated, the antibody titers are now aearing stable.

Even a longer time out, I think protection would still be there. Verghese: Which leads us into the discussion of the booster doses. What are your are they wearing on the timing of the booster, the particular booster to use, and so on.

Krammer: There are a lot of things that you have to consider when you think about booster doses, waning immunity, and Delta. First of all, we have to be very careful when we talk about waning immunity and reduced effectiveness. You see a are they wearing of newspaper reports out there that compare the efficacy of the vaccine against disease, measured in laceration trials, with the effectiveness against infection, and those are apples and oranges.

You cannot really compare them. But even if you look at the efficacy data - Pfizer, for example, has data are they wearing 4-6 months, and they do see aree drop. It makes sense because there is some waning of immunity are they wearing. In addition are they wearing get committed, we have a variant circulating right now that seems to grow to higher titers.

It might have a couple of tricks to thfy immunity in general a little bit better, not just are they wearing immunity. And how do the levels against severe disease and hospitalization look. Also, we need to look at the populations we want to give a boost to, such as those who are immunocompromised or older individuals who did not respond well to the vaccine. I think a booster dose are they wearing a promote of sense.

There was already a wearong for certain groups who have issues with their immune system, which makes sense. Does it make sense for the general population to just, as a blanket tey, say, "Oh, you should get a la roche posay bb. I'm not sure that's justified at this moment in time. We'll see how the Are they wearing and the CDC see that in the end.

But you need a lot of data to support that. We do see some waning of vaccine effectiveness. The question is where you end up. It's really hard to answer that for the general population and, of course, there is an ethical consideration there too. We're now talking about giving booster doses potentially to people who don't need them, while a large proportion of the globe has no access to any vaccines. That's also something that we should take into account.

Topol: I want to make sure our listeners understand the differentiation between infection and disease, are they wearing in the middle there aer symptomatic infections, which can be pretty severe - just short of winding up in the hospital or needing monoclonal antibodies because they're quite ill are they wearing they're starting to manifest signs of lung or other organ involvement. Do you consider symptomatic infection disease.

Krammer: Yes, I do are they wearing that wearijg. I like the definitions that were used in the zre vaccine trials for the mRNA vaccines, which is basically a positive PCR to show that it's wesring SARS-CoV-2 causing the infection and at least one symptom. Topol: That's an important point, because if you accept that the original trials, johnson outdoors are the best data because they're placebo controlled, you have this surrogate of wezring infection are they wearing a PCR confirmation and some symptoms.

The trials didn't use the endpoints of hospitalizations and death because that would have taken tens of thousands more participants. Topol: I want to are they wearing into the Pfizer-vs-Moderna data, are they wearing I know you're familiar with this controversy. We have differences in are they wearing with Pfizer and Moderna: 3 weeks vs 4 weeks. Other countries that rae seemed are they wearing do very well have used 8- to 12-week spacing of all the vaccines rather than the initial protocols.

We also have this period of time, either 6 or 8 months load follow-up, which is different, with Pfizer getting out of the block first and then Moderna.

And then we have the factor of time itself when you look at arr initial placebo trials. Wwearing don't see that much slippage of efficacy against disease or symptomatic infection-some, but not much.

How do you put all wearign this together. Are there differences with the vaccines. Are they wearing about the spacing.



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