The reason we do a second vaccination is that these later doses help to solidify immune memory, in part by giving extra training to the cells that produce antibodies, a process called affinity maturation. But this process begins with the single dose, and the evidence collected between the time of the 1st and 2nd doses in 10Ks of people in the Phase 3 trials suggests that the level of affinity maturation may provide enough protection to meet the standards we have set for vaccine approval during this pandemic even without the 2nd dose. we should begin immediate single-dose trials, recruiting volunteers from low-risk populations who are 1st in line for the vaccinations.
Magical extra doses and supply chain optimization:

some of the vaccine distribution sites had access to low dead-volume syringes, syringes that leave less vaccine trapped between the plunger and needle — the “dead volume” — after a shot is given. Thus, less vaccine was wasted in the syringe and more available for putting into arms using the low dead-volume syringes.
This is quite remarkable. Increasing vaccine supply by 20% by building more factories could cost billions. We should do that, it would be worth it. But in this case, we managed to increase supply by at least 20% use a relatively inexpensive redesign of the syringe. What this indicates is the importance of thinking along the entire supply chain for opportunities for optimization.
Single-Shot and first doses first
The FDA panel voted unanimously to authorize the J&J vaccine. Good. Note, however, that the single-shot J&J vaccine is quite comparable to the first dose of the Pfizer and Moderna vaccines. Yet, few people are demanding that J&J be required to offer a second shot at all, let alone in 3-4 weeks (What about vaccine escape! How long does immunity with a single-shot last! What about the children!). It really is scandalous how these objections to a single-shot have disappeared. This is evidence of what I call magical thinking–an undue focus on the clinical trial design as having incantatory power.
Why did J&J focus on a single-shot? Was this because of “the science”, i.e. something unique about their vaccine? No. J&J focused on a single-shot vaccine for the same pragmatic reasons that I favor First Doses First.
J&J chose to begin with the single shot because the World Health Organization and other experts agreed it would be a faster, more effective tool in an emergency. (emphasis added).
Since that time, Dr Dolittle has insisted we stick to the 2 shots regime. Criminal negligence.
Fractional doses work
in an article on new vaccine boosters there is this revealing statement:
Any revised Moderna vaccine would include a lower dose than the original. The company went with a high dose in its initial vaccine to guarantee effectiveness, but the company is confident the dose can come down, reducing side effects without compromising protection.
Arrgh! Why wait for a new vaccine??? Fractional dosing now! The article also notes:
One of Moderna’s co-founders is known for his research on microneedles, tiny Band-Aid-like patches that can deliver medications without the pain of a shot. Moderna has said nothing about delivery plans, but it’s conceivable the company might try to combine the 2 technologies to provide a booster that doesn’t require an injection.
The skin is highly immunologically active so you can give lower doses with a microneedle patch. The microneedles are sometimes made from sugar and don’t hurt.
Dose stretching works extremely well
A new paper on dose-stretching makes 3 big points. First, “Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.” Future vaccines may not have to go through lengthy clinical trials but can instead rely on these correlates of immunity.
A 50% or 25% dose of the Moderna or Pfizer vaccine looks to be more effective than the standard dose of some of the other vaccines like the AstraZeneca, J&J or Sinopharm vaccines. The point is not that these other vaccines aren’t good–they are great! The point is that by using fractional dosing we could rapidly and safely expand the number of effective doses of the Moderna and Pfizer vaccines.
Second, even if efficacy rates for fractional doses are considerably lower, dose-stretching policies are still likely to reduce infections and deaths. A 50% dose strategy reduces infections and deaths under a variety of different epidemic scenarios as long as the efficacy rate is 70% or greater.
Third, it is better to start vaccination with a less efficacious vaccine than to wait for a more efficacious vaccine. Thus, Great Britain and Canada’s policies of starting First Doses first with the AstraZeneca vaccine and then moving to second doses, perhaps with the Moderna or Pfizer vaccines is a good strategy.
