Note: There will be no Q&A tomorrow. Happy Dr. Martin Luther King Jr. Day!   

Question: Well, it appears that we are going to run out of vaccines for a time and that means some folks will be left with more time between their first and second doses than recommended.  So I guess my question is, what do we know from other vaccines about larger than recommended spacing between the first and second dose?  

Answer: I’m not sure that we’ll run out of vaccines since production is supposed to be ramping up, but it’s a real possibility.  Unfortunately, it is extremely challenging to know what’s going on with the US vaccine stockpile.  We had understood that the USG held back distributing half of all vaccines in the stockpile for 2nd doses.  In fact, just earlier this week HHS Sec. Azar stated that the administration would be “releasing the entire supply for order by states, rather than holding second doses in reserve.”  As a result, states ramped up distribution capacity and invited a wider range of priority populations to make appointments for vaccination.  By Friday, it became clear that all doses had already been distributed. Sec. Azar stated, “No. There’s not a reserve stockpile.”  What a mess.  

As to your question, we talked about changes to vaccine schedule in our Q&A of 1/6, but did not examine evidence from other vaccines.  WHO offers this helpful set of recommendations for interrupted or delayed routine immunization (Table 1).  As far as I understand it, the main issues are these five, for which I’ve provided a few examples (non-exhaustive!) as related to other vaccines:

1. Partial vaccination likely offers only partial immunity (i.e. people are still at some risk of disease after 1 shot)
   • For example, the measles vaccine requires 2 shots.  The first shot offers a great deal of protection (93% effective at preventing measles) but the second shot boosts the protection to 97%.  For polio, the difference is greater with one dose having the protective efficacy of about 50% but two doses being about 80%-90% and 3 doses being 99%-100% effective. 
2. Delaying/confusing the timing of 2nd dose could mean much greater loss to follow-up (i.e. many people only get 1 shot and remain at risk of infection/disease); 
   • In a study of vaccine delay among children, researchers found “Children whose parents intentionally delayed were significantly less likely to receive all vaccines by 19 months of age than children whose parents did not delay (35.4% vs. 60.1%, p<0.05).”
3. A partial immune response could push the virus to mutate faster; 
   • As described in this 2012 paper, “Partially effective immune response enough to exert selective pressure, but not effective enough to suppress escape viral mutants is the most effective driving force of antigenic variation.”    
4. Changing the dosing schedule without adequate evidence could increase vaccine hesitancy (i.e. by confirming fears about the scientific rigor of the vaccine efforts);
   • Among parents who express vaccine hesitancy about childhood vaccination schedules, perceptions of safety are a big driver of concerns.  With regard to COVID, efforts to push vaccines out more quickly by changing the dosing schedule could reduce public trust.  
5. Some interrupted vaccines require repeat of the 1st dose, though unlikely with the COVID vaccines, if it were the case, it would add more stress to vaccine production/ distribution/ administration.  
   • As shown in Table 1, most interrupted vaccines resume without repeating the first dose.

Table 1. WHO Recommendations for Interrupted or Delayed Routine Immunization (Sept. 2020)