A third dose?

There’s been a pretty dramatic run of events in the past week re: booster shots in the US. For those of you who have not closely followed, this is what’s happened thus far:

• June 25: During an ACIP meeting, Dr. Sara Oliver delivered a fantastic presentation (as per usual) stating that the CDC will not suggest a booster until one of two things happen:

  1. Evidence of declining protection against illness, such as declines in vaccine effectiveness. NOT only waning antibody response

  2. An escape variant (variant of concern substantially impacting vaccine protection)

• July 8 (Thursday): Pfizer announced it will seek emergency use authorization (EUA) for a booster shot due to new evidence regarding reduced vaccine effectiveness

• July 8 (Thursday): The CDC and FDA quickly released a counter statement saying there is no evidence for a third shot at this time

• July 12 (today): Key players from both sides had a closed door meeting to discuss Pfizer and FDA/CDC’s differing opinions.

So, what did they discuss during the meeting today?

I’m guessing three topics came up…

First, Pfizer said there was evidence for waning antibodies. They cited an Israeli study showing a decrease in vaccine effectiveness (specifically against symptomatic disease) 6-months post inoculation. Further, they said an internal Pfizer study showed that a booster could give us “5 to 10 times higher response than two doses”. These two studies are not publicly available yet. But even without them, we know that antibodies (COVID19 or not) naturally decrease over time. And the rate in which they decrease is highly dependent on the initial efficacy rate. Because Pfizer started with such a high efficacy (94%), it will take longer for antibodies to wane compared to less efficacious shots. Also, antibodies are important but they are not the whole story. Two other types of cells, T-cells and memory B-cells, hold the key to long-term immunity. Unfortunately, they are a lot more difficult to study.

Second, Pfizer referenced the Delta variant for the need of a booster shot. I’ll be honest, though, I’m not entirely sure why. We have pretty solid evidence that our mRNA vaccines work against Delta. It’s protecting decently against symptomatic disease but, more importantly, protecting against severe disease.

Third, I assume the discussion then turned to an even more important debate: Do specific populations need a booster?

Since April, France has handed out boosters to cancer patients and others with immune system impairments. Israel also started three-dose regimens this week. Other countries, like the UK, are planning to administer booster shots in September to older populations (70+), healthcare workers, and 16+ that are immunocompromised.

There is plenty of scientific evidence demonstrating that some immunocompromised groups don’t get full protection from the COVID19 vaccines. This is especially true among organ transplant patients, some cancer patients, and some patients using immunosuppressive drugs.  

So, several research groups have studied the impact of a third shot among specific immunocompromised groups:

• A French study found that the number of organ transplant recipients who had antibodies increased from 40% (after two doses) to 68% (after 3rd dose). Out of 59 patients, 33 (56%) remained without antibodies after the third dose.

• An American study among organ transplant patients found that among 24 patients with no antibodies after the second vaccine dose, 6 (25%) patients had high levels of antibodies after the third dose. 16 (67%) patients had no antibodies after the third dose.

So, a third dose helps a little but not a lot. It could also help on a population-level. Emerging evidence (here, here, and here) suggest that immunocompromised individuals act as incubators for mutations. For example, the first documented case of B.1.526 was found in a patient with advanced AIDS.

So, do we get a third shot?

The scientific evidence says we don’t need one right now. At least for the general population. As we know, scientists continually reevaluate the situation, so this may change tomorrow or this may never change. Today, we don’t need it. The need for a booster for specific populations is another question.

Other important considerations into this policy debate include:

• Global vaccine equity. In other words, could that third dose be better used in other countries so we stop this virus from spreading quickly (and thus mutating)?

• Time. The application takes a while and, in a month or so, we may have more data or a new variant. So, one might argue that this is a proactive approach.

• Profits. One also can’t help but think that big pharma will financially benefit from a third dose.

Nonetheless, Pfizer can apply for a booster EUA. This certainly doesn’t mean that the FDA and/or CDC will approve it. It would be beneficial for everyone to get on the same page though. And hopefully that was the result from the meeting today. Only time will tell.

Love, YLE