Last week the New England Journal of Medicine published a perspective announcing a milestone in the pandemic. Also, we reached another milestone of sorts with the authorization of bivalent covid vaccines down to 6 months of age. I think the milestone designation is a bit overhyped, but the topics are worth exploring.
Vaccine Correlate of Protection (CoP)
The NEJM blurb's title was a bit misleading, saying this milestone had been attained. It depends on how you define CoP, but at this point we don't have an antibody or other cutoff that anyone can point to as a true CoP. The authors acknowledge this in the text. It's worth thinking about what we have so far and what barriers we face in finding a true CoP for covid.
Healthcare providers pretty much know that multiple measures of immune response can be analyzed, but it's quite a challenge to figure out which of those measurements correlate with protection. It is clear that both serum anti-spike IgG antibody and anti-SARS-CoV-2 neutralizing antibody titers correlate pretty well with protection from infection and illness; the higher the titer, the less likely the outcome will occur. However, there is still no specific number to predict with reasonable confidence that an individual is protected from a specific outcome. The reasons (and barriers) are multiple: 1) covid is a respiratory mucosal infection that can be invasive into the bloodstream - mucosal antibody might be a better target for a CoP, but that is a much more difficult set of circumstances; 2) antibody levels decline after vaccination, so an individual's titer at one point in time is going to fall fairly quickly; 3) assays have been performed in different labs with slightly different techniques - the lab methods need to be standardized going forward; and 4) the current CoPs were obtained primarily from data on previously uninfected subjects who received anti-spike vaccines before omicron and even delta variants had appeared - sort of a moving target or wack-a-mole problem we've faced with covid all along.
All this aside, even the current CoPs are extremely helpful to evaluate and approve newer version of covid-19 vaccines.
Bivalent Vaccines Authorized for Younger Children
FDA has authorized, and ACIP recommended, that both Pfizer and Moderna bivalent vaccines now be used for booster/third dosing in children starting at 6 months of age. Details are available at the linked websites. The endpoint for the current authorization is age 5 years for Pfizer and age 6 years for Moderna, just because of different age cutoffs used for the original vaccine trials by the 2 companies. The wording is a little confusing due to the nature of prior authorizations of the monovalent vaccines.
Moderna's monovalent vaccine was originally authorized as a 2-dose series based on immunogenicity, safety, and efficacy data in children ages 6 months through 5 years. Thus, the Moderna bivalent vaccine is designated as a booster dose to be given at least 2 months after the 2-dose primary series is completed.
Conversely, the Pfizer dose is not a booster, but is considered part of a 3-dose primary series. Pfizer's original studies of the monovalent vaccine in this age group did not meet immunogenicity targets in the 2- through 4-year-old age group and thus was eventually authorized as a 3-dose series for the 6-month through 4-years age group.
Don't let this confuse healthcare providers or families. Essentially both Pfizer and Moderna dosing should be considered as a 3-dose package. Whether the third dose is called part of the primary series or a booster shouldn't matter in practical terms. I'm hoping CDC and ACIP will clarify this in their online materials for families.
I don't see any compelling reason to favor one product over the other in this age group, I would just recommend choosing whichever is more convenient to obtain. A bigger problem is the extremely low vaccination rate in this population. (You will need to click the "Age" tab in the first graph section to see the data.)
Who Cares About Milestones Anyway?
In a relatively short time I will achieve what some people call a milestone, becoming a septuagenarian. I don't plan on feeling any differently. For this whole milestone thing, I can only say, Bah! Humbug!