Yesterday, August 12th 2021, the Food and Drug Administration “authorized” an extra vaccine dose for the Pfizer and Moderna mRNA vaccines for those who have received organ transplants (this had already been recommended) and “some people with weakened immune systems.” (link: https://www.washingtonpost.com/health/2021/08/12/booster-shot-coronavirus/).  The process by which these doses will be made available to the public is, theoretically, going to be worked out at a CDC meeting today, Friday the 13rd.  Not exactly an auspicious start.

So what were the FDA thinking and to whom do these recommendations for a booster apply?  

At its core, the Biden Administration seems to be folding under the relentless PR pressure generated by Pfizer suggesting a drop in vaccine efficacy (defined: degree to which a vaccine prevents disease, and possibly also transmission, under ideal and controlled circumstances – comparing a vaccinated group with a placebo group) over time.  Their paper, which has not undergone peer review, (link: https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v1.full.pdf) shows robust vaccine efficacy at 6 months and concludes the following among 44,000 participants over age 16 and 2000 participants aged 12-15 (note that this study group received their vaccination as early as July 27th 2020 and as late as January 12th, 2021):

1. Vaccine Efficacy against COVID-19 was 91% (95% CI 89.0‒93.2) through up to 6 months of follow-up
2. Vaccine Efficacy of 86%‒100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. 
3. Vaccine Efficacy against severe disease was 97% (95% CI 80.3‒ 99.9). 
4. In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) Vaccine Efficacy was observed. 

That sounds pretty good, right?  Considering that 18 months ago we would be doing backflips over a vaccine that had 50% (annual flu shot) to 70%, it seems that 91% at 6 months is excellent. For those interested in an excellent summary of vaccine efficacy, please refer to this WHO link:  https://www.who.int/news-room/feature-stories/detail/vaccine-efficacy-effectiveness-and-protection

The Biden Administration and the FDA are concentrating on this sentence in the referenced Pfizer paper:

“From its peak post-dose 2, observed Vaccine Efficacy (VE) declined. From 7 days to <2 months post-dose 2, VE was 96.2% (95% CI [93.3-98.1]); from 2 months to <4 months, VE was 90.1% (95% CI [86.6- 92.9]); and from 4 months to the data cut-off, VE was 83.7% (95% CI [74.7-89.9]).”

There are a ton of limitations to this observation, the first being that high not the least of which is a much wider confidence interval for the 83.7% estimate.  Notice that for the Vaccine Efficacy estimates from 7 days to 2 months that the 95% confidence interval is about 5 percentage points.  This is essentially the same (6 percentage points) for the 2 month to 4 month estimate.  However, for 4 months and beyond we are looking at a confidence range of 15% – meaning that the vaccine efficacy could be as high as 89.9%. Typically wide confidence intervals are due to fewer observations and, in fact, on careful inspection of the data (Figure 2; page 15) only 12,670 remain in the vaccinated group (started with 23,040) and 11,802 remain in the placebo group (started with 23.037).  Remember too, most of those who were in the placebo group have now been vaccinated.

The authors themselves note “preliminary analyses of breakthrough cases have not yet identified a correlate of protection, as vaccine protection rates remain high.”  Further, “early protection against COVID-19 without robust serum neutralization indicates that neutralizing titers alone do not appear to explain early BNT162b2- mediated protection from COVID-19. Other immune mechanisms (e.g., innate immune responses, CD4+ or CD8+ T-cell responses, B-cell memory responses, antibody-dependent cytotoxicity) may contribute to protection.”

Remember too in all of this – protection against severe disease remains at 97%.

A very fuzzy interpretation of these data are offered by Pfizer CEO Albert Bourla (who interestingly is a veterinarian with a PhD in Reproductive Biotechnology – so perhaps has good insight into ‘herd’ immunity):

“There is very good protection in the beginning, and then there’s waning. And when you come closer to six months, [waning] which is even more profound with delta [variant],” Pfizer chief executive Albert Bourla said. “The waning is … more profound for mild cases, but there is a clear waning also for hospitalizations and severe disease.”

I’m not sure which paper he is reading as the one offered has no data at 6 months (only greater than 4 months) and does not offer any subtype analysis when it comes to the delta variant, rather references only the South African (beta variant).

But practically, what does this mean? The FDA has linked their booster recommendation to those individuals with “a similar level of immune-system impairment” as those who have undergone organ transplants.  This should encompass about 2.7 percent of U.S. adults, according to the CDC, or about 7 million people, are immunocompromised. Some, like transplant patients, take immune-suppressing drugs to prevent organ rejection. Others have blood cancers and other illnesses that damage the immune system. Still others are on cancer chemotherapy.

As noted above, the CDC’s Advisory Committee on Immunization Practices is expected to vote to recommend the extra doses on Friday and to give further details on how they will be administered. The panel also is likely to urge patients to talk to their doctors about the additional shots – but without specific guidance from the CDC, it is unclear what advice doctors will offer.

 In reality, there is no process for ‘qualification’ or ‘authorization’ for a booster dose so really it will be left up to patients to self-identify.  Record keeping for boosters itself will be left to patients as, in California, there is no methodology to distinguish a third ‘booster’ dose from a routine first or second. There is no authorizing body, no prescription to be written. With a paper-based system, those coming in for a third booster will present themselves and be recorded as a new first dose – a process which will artificially inflate estimates of vaccine coverage across the state.