There's been some discussion about whether #COVID19 #vaccines should be rolled out as 1 dose instead of 2 (or lower doses). We call this a "dose-sparing" strategy, and it's been used before during outbreaks in the setting of vaccine shortages - notably yellow fever. 1/11

A few years ago, Brazil had a terrible yellow fever outbreak, but there was (and is) a severe YF vaccine shortage. Based on thoughtful @WHO guidance, Brazil gave 1/5th the standard dose. There are lessons from this strategy that I think can be helpful for the current debate. 2/11

First, this @WHO document outlining the pros and cons of fractional YF vaccine dosing (with little data, in a crisis) provides a framework for the discussion - we don't need to reinvent the public health wheel for these complicated issues. 3/11 https://apps.who.int/iris/bitstream/handle/10665/246236/WHO-YF-SAGE-16.1-eng.pdf;jsessionid=BABA0B361CF3F1BA2A1DDD5A20084054?sequence=1

Second, the Brazil example shows there is precedent for rolling out a vaccine strategy that is unapproved and not tested in an efficacy trial. So, there is not hard and fast rules about what we can do as a society when faced with difficult choices. 4/11

However, yellow fever vaccines are very different than COVID19 vaccines - why? Because there are clear "correlates of immunity" for yellow fever. They had very small studies looking at fractional dosing, but the data was more interpretable. Antibody levels hit a known target.5/11

For COVID19 we don't yet know our immune target, what antibody level or type is needed. We WILL know it, but probably not for another 6 weeks. So, it's harder to interpret small immuno data, and efficacy data is short f/u so far 6/11

The second reason why the Brazil example doesn't apply to us (in addition to the immune correlates piece) is that Brazil had the infrastructure in place for distribution and vaccination. Not perfect. But existed. This is not our situation right now. 7/11

Finally, WHO was very clear that one of the major risks to applying an untested dose-sparing regimen was potential damage to credibility. They worried that rolling out a vaccine that people perceived to be less effective (and experimental) could jeopardize the entire program.8/11

Ultimately, the Brazil example tells me that dose-sparing during a pandemic is an option, but that the risks and benefits need to be addressed square-on. In my view, the benefit for mRNA vaccines is likely small, since we can't distribute the vaccines we have as it is. 9/11

It probably will increase coverage a little, and I'm sure it's partially protective. But this is uncertain and may be only a marginal improvement. Especially when, IMO, the risks are quite large - the biggest risk being to credibility. 10/11

Vaccine mistrust and low uptake work hand in hand with poor distribution to sabotage all of our best efforts. No dose-sparing strategy can overcome those challenges, and that's where our focus should stay. 11/11