August 17th, 2021

C19 Weekly Briefing Supplement on the importance of maintaining high circulating levels of neutralizing antibodies through vaccine boosters.  

Booster Shots

The new wave of the pandemic is being driven by Delta which bypasses prior immunity at a higher rate than any previous variant.  How is Delta managing to do this?  It appears likely that some combination of mutations allow it to escape key neutralizing antibodies while affording it the ability to generate more viral copies (viral titers among people infected with Delta are 1,000 times higher than those of people infected with the original strain of the virus), combined with timing.  People have the highest level of neutralizing antibodies shortly after getting vaccinated or infected and then those levels wane gradually over months until they are low enough to allow for breakthrough infections.  It is likely that those who were vaccinated or infected several months ago have less immune protection against getting infected than those who were vaccinated or got infected more recently.  

The process of getting C19 starts with exposure–a person inhales viral aerosols that stick to mucous membranes in the nose, nasopharynx, or lungs.  This is called colonization.  If someone has high levels of circulating neutralizing antibodies in the immune system of the mucous membranes (called the "MALT"), they can kill off the virus before it penetrates into the body's interior to cause an infection.  This is what happens in most people who were recently vaccinated.  However, as circulating neutralizing antibody titers wane over time, the MALT has fewer soldiers to keep colonization contained and this allows breakthrough infections to occur.

There are now sufficiently ample data showing that an additional shot of vaccine boosts circulating neutralizing antibodies to levels much higher than those seen after completion of the initial vaccination regimen.  This should provide those who get booster shots with much stronger protection against getting infected (lots of neutralizing antibodies circulating in the MALT).  And there have been no reports of adverse events from receiving a third shot of mRNA vaccine or a second shot of Janssen vaccine.  So what's the delay and why are so many experts still not recommending booster shots across the board?  Three reasons have been given: 

1. It isn't fair that some people get a third shot when others have not received even one shot.  This is the argument the WHO is making against boosters in rich countries.  And on a global level, they have a good point.  But this is not a scientific argument and domestically, we have more vaccine here than people who want it.  In fact, we are throwing out thousands of doses every day.  Why not make use of them instead of throwing them away? 
2. Breakthrough infections rarely lead to severe disease because B and T cells are durable and once the infection takes hold in someone who has been vaccinated, it is very unlikely to land them in the hospital and extremely unlikely to kill them.  Therefore, since breakthrough infections are less severe, boosters are not needed.  True, but C19 is a disease with at least two and possibly three phases.  The first is the acute viral phase when some people get very sick and die.  The current standard vaccination regimen, as stated, is sufficient to protect against this.  The second is the post-viral phase when about 30% of people struggle with ongoing physical and mental symptoms (long-covid).  And a potential third phase to the disease has yet to be seen: what happens down the road to patients whose hearts, brains, blood vessels, lungs, etc., have been damaged by the primary infection?  Will they develop higher rates of cardiovascular or Altzheimer's disease?   These latter two phases of C19 can happen to people who have mild or even asymptomatic viral periods and there is no indication that this will not happen or will happen less often among vaccinated persons who experience breakthrough infections.  
3. We don't yet know if boosters will help, harm, or do nothing because large scale Phase III clinical trials have not been conducted.  That's also true, but there are significant preliminary data showing boosters to be both safe and likely highly effective at helping prevent infections and no data to suggest otherwise.    

The focus of most public health and infectious disease experts has been on the acute viral period of C19.  That's largely because, while some other infections can cause long-term health consequences, most do not, and most doctors by training are concerned about preventing severe illness and death.  But C19 has shown itself to be different from other common RTIs in so many ways (it's airborne, it's more contagious, it's more deadly, it shape-shifts more quickly than expected, etc.) and the fact that it causes such a high degree of chronic and potentially chronic illness is just one more distinguishing feature of this novel virus.  It is not unreasonable to be concerned that in the end, the second and third phases of C19 will wind up taking a larger toll on society than the (sometimes deadly) first phase.  If boosters were available today, I'd take one immediately.  

943. Iceland recommends booster shots for all citizens who got Janssen at 8 weeks post-vaccination.  
https://www.landlaeknir.is/um-embaettid/frettir/frett/item47133/maelt-med-orvunarbolusetningu-fyrir-einstaklinga-sem-fengu-covid-19-boluefni-janssen

944.  Moderna seeks authorization of the first variant-specific booster shot; but it's tuned to Beta, not Delta.  
https://www.healio.com/news/primary-care/20210225/moderna-sends-variantspecific-vaccine-to-nih-for-clinical-study

945.  Pfizer submits data from Phase I clinical trials on booster doses which they now recommend for the general population.  Boosters triggered the production of significantly higher levels of circulating neutralizing antibodies against Delta.  
https://www.cnbc.com/2021/08/16/covid-vaccine-booster-shot-pfizer-submits-data-to-fda-for-approval.html

946.  Dr. Fauci: "Everyone will need a booster shot."  
https://www.cnbc.com/2021/08/12/covid-booster-shot-fauci-says-it-is-likely-everybody-will-eventually-need-a-third-vaccine.html

947.  Israel is now doing booster shots for all persons 50 and over and for all healthcare workers. 
https://www.voanews.com/middle-east/israel-rolls-out-covid-booster-shots-anyone-over-50

948.  Biden Administration to approve booster shots for most Americans at 8 months post-vax, beginning with healthcare workers. 
https://www.nytimes.com/2021/08/16/us/politics/booster-shots.html