As my antibodies slowly decline, I have been thinking about long-term efficacy of the RNA vaccines against the B.1.351 (SA) variant. As one of the trial guinea pigs, I’m eight months out from my second Pfizer shot.
The NIH recently published a study in which Moderna trial volunteers who were 6 months out from their second shot gave some blood so that their antibodies could be tested against some of the variants of concern. The researchers did multiple different tests on these antibodies, and for all of them, the SA variant was the most successful at evading the antibodies.
At six months, the difference between how well the antibodies performed for the older and SA variants narrowed compared to earlier time points. This is to be expected, because your immune system initially makes “first run” antibodies and then later comes up with better ones. It then lets the weaker ones decline and keeps the better ones for long-term immunological memory. This means that people who have low antibodies because they have declined, and not because their response was weak to start off with, probably have higher-quality antibodies. For example, one of the tests they ran was the ability of the antibodies to block binding of spike to the ACE2 receptor. At day 43 (two weeks after the second shot) the antibodies were 28 times worse at blocking binding to the B.1.351 spike than the older spike. At day 209 (6 months after the second shot) they were only 9.1 times worse. That’s still a pretty big difference, but it’s a lot more manageable than 28x. If the Roche/Labcorp antibody test needs to be at least 20-50 to have some efficacy against the older variant, it needs to be 9.1 times that (182-455) to have some efficacy against B.1.351, at least for the specific function of blocking binding of the spike to the ACE2. I’ve written before that 50 is a reasonable point to start thinking about a booster, because it means that you’re probably a few months out from having no immunity against infection at all. I don’t like 182-455, because it sounds really specific, and in reality this is a rough estimate. I’m going with 200-500, to round to the nearest hundred, and hopefully communicate the level of uncertainty that way.
As I’ve written before, preventing binding to the cell is not the only way that antibodies can prevent infection, and those other antibody functions are likely to be less affected by the mutations in the variant. When the NIH group looked at simple binding of the antibodies to the spike at six months, the B.1.351 variant was only about 2-fold weaker. So I consider 200-500 to be a worst-case scenario for the threshold. It may well be that the real number needed is lower. But I don’t think that it’s likely to be much higher, assuming that one has had an initial strong response and declined to this level at six or more months. The AZ vaccine (28 day spacing) starts at about 500 and unfortunately has no efficacy against infection with B.1.351. (I haven’t seen data yet for efficacy against severe disease.) It may also be possible that at longer than six months, overall antibody quality will be even better, meaning that one can get by with even lower levels. As an aside, the J&J vaccine is designed to give higher-quality antibodies from the start, so even though total antibody levels are lower than AZ, J&J has pretty good efficacy against B.1.351 (64% efficacy against moderate-to-severe covid). Pfizer ran a randomized controlled trial in SA and had 8 cases, all in the placebo group, but of course those were recently-vaccinated people. But it does fit in that most people who get Pfizer are well over 500 on the Roche/Labcorp test initially. A study of the Pfizer vaccine in Qatar found 75% efficacy against infection with B.1.351 and 97% against severe/critical disease with it. That one was not randomized, and so the vaccinated group may have been people who were at higher risk of infection.
I also found a very interesting study from a hospital in Luxembourg. They had an outbreak of B.1.351, and four healthcare workers who had had covid before B.1.351 was in Europe caught it. Those four had taken the Roche/labcorp antibody test before catching B.1.351, and so we know what antibody levels failed for them. They were: 74.2 (about a month before the second case), 25 (about a month and a half before the second case), 68.9 (about a month before the second case), and 131 (a few weeks before the second case.) Of course, we don’t know anything about the quality of those antibodies, but they are all lower than my proposed 200-500 range, so this fits with the way I’m thinking about this problem so far. All four of these were young people (20s and 30s) and symptoms were no worse for the second infection than the first.
While I was reading these papers, my Labcorp results came back, and my antibodies are at 357. Because my state is pretty much all B.1.1.7 right now, I don’t feel the need to go get a booster. But I am planning to move somewhere with a lot of B.1.351 in January, so I definitely will get the B.1.351 variant booster when it comes out. Both Pfizer and Moderna are working on B.1.351 boosters.
Memory B and T cells would probably help protect me against severe disease, even if I didn’t get a booster. Those memory cells can reactivate and start making more antibodies within days. That boost of antibodies is something like the infusion of Bamlanivimab given to high-risk people within the first few days, but better because the antibodies you make are more diverse and your immune system makes them for free. In the clinical trial of Bamlanivimab, it cut the risk of hospitalization by about 75%. So getting an early boost of antibodies is not a guarantee that you won’t have severe disease, but it helps a lot. And the vaccine might give an added benefit against severe disease from T-cell memory, even without a booster.
The advantage of keeping my antibodies up is to keep my risk of infection low. Probably if I got an infection, it would be mild, but I’d rather prevent the infection entirely if I have the option. And aside from the benefit to me, it will help prevent me from spreading the virus to someone else. My immune system is generally well-behaved, and my reaction to the vaccine was not severe, so I don’t think there is much downside in getting another dose.
NIH study of Moderna at six months: https://www.biorxiv.org/content/10.1101/2021.05.13.444010v1.full.pdf
Bamlanivimab trial: https://www.nejm.org/doi/full/10.1056/nejmoa2029849
J&J efficacy: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2101544
Efficacy of Pfizer against B.1.351 in Qatar: https://www.nejm.org/doi/pdf/10.1056/NEJMc2104974
Efficacy of AZ against B.1.351: https://www.nejm.org/doi/full/10.1056/NEJMoa2102214
Pfizer in SA: https://www.nature.com/articles/d41586-021-01222-5
Four reinfections in Luxembourg: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.18.2100423