Pfizer: Our vaccine neutralizes Omicron after three doses but is shakier after two

AP Photo/Mark Lennihan, Pool

Good news, although it’s naturally being spun by some vax skeptics as part of a con. “Aha. Of course they want us to get another $hot.”

If instead the company had come out and said that the booster doesn’t work, the reaction would be, “Aha. Of course they want us to get an updated Omicron $hot.”


The skeptics can take their chances with natural immunity. For the rest of us, three doses produces enough neutralizing antibodies in lab studies to provide as much protection against Omicron as two doses provided against the original Wuhan strain of the virus. Which, I’m guessing, means that Pfizer won’t end up producing an Omicron-specific vaccine after all. There are costs to doing that, scientific and financial. If the current formula works after three doses, why tinker with it?

The real news here is that two doses might suffice to protect people from severe illness after being infected with Omicron. Given that the variant appears to produce milder symptoms than Delta to begin with, those who’ve had two doses but are ambivalent about getting a third might be okay with what they have.

Sera from individuals who received two doses of the current COVID-19 vaccine did exhibit, on average, more than a 25-fold reduction in neutralization titers against the Omicron variant compared to wild-type, indicating that two doses of BNT162b2 may not be sufficient to protect against infection with the Omicron variant. However, as the vast majority of epitopes targeted by vaccine-induced T cells are not affected by the mutations in Omicron, the companies believe that vaccinated individuals may still be protected against severe forms of the disease and are closely monitoring real world effectiveness against Omicron, globally.

A more robust protection may be achieved by a third dose as data from additional studies of the companies indicate that a booster with the current COVID-19 vaccine from Pfizer and BioNTech increases the antibody titers by 25-fold. According to the companies’ preliminary data, a third dose provides a similar level of neutralizing antibodies to Omicron as is observed after two doses against wild-type and other variants that emerged before Omicron. These antibody levels are associated with high efficacy against both the wild-type virus and these variants. A third dose also strongly increases CD8+ T cell levels against multiple spike protein epitopes which are considered to correlate with the protection against severe disease. Compared to the wild-type virus, the vast majority of these epitopes remain unchanged in the Omicron spike variant.


In graph form:

You’re much better protected against infection and severe illness from Omicron if you’ve had three shots but you might be protected from severe illness if you’ve had two. Logically, that points away from developing an updated vaccine and towards telling the public, “Get a booster ASAP or take your chances and hope for the best.” Which is the message that’s circulating among relevant authorities this morning:

There are three catches with Pfizer’s results, though. The first is that this was a lab study, testing blood taken from vaccinated people against the variant in vitro. That gives scientists a sense of how effective antibodies will be inside the body but they’ll need actual clinical trials to know that for sure.


The second catch is that the blood they used to run the study was taken from people who’d only recently received their second or third doses:

How well protected are you from Omicron if you were boosted three months ago, say? Presumably your antibody levels have already begun to wane by now.

The third catch is that Pfizer’s study is just one of four that appeared overnight testing how well antibodies produced by its vaccine fare against Omicron. I wrote about another from South Africa last evening that showed neutralizing antibodies were 40-fold less effective against the variant after two doses. Notably, that South African study used a live version of Omicron; Pfizer’s study used a “pseudovirus” that they engineered in the lab to mimic Omicron.

Of the four studies testing Pfizer’s vaccine against the variant, the ones using the actual virus show a much steeper drop in antibodies’ ability to neutralize Omicron than the ones using a pseudovirus do.


Note the Ciesek study in particular, which found a roughly 30-fold loss in neutralizing protection *even among the boosted* when antibodies were pitted against the live Omicron virus. That’s a lot different from Pfizer’s encouraging data using the pseudovirus.

So maybe a new Omicron-specific vaccine isn’t off the table after all.

Here’s Scott Gottlieb, a Pfizer board member, emphasizing that even two doses will provide some protection.

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