How Many Boosters are too Many? Original Antigenic Sin? Get that 4th Shot! (When the Time Comes)

(CNBC) Is the best strategy against omicron to boost with the original vaccine? Quoting Dr. Paul Offitt,

“The question is, if you keep priming and boosting with a strain, which is basically to make an immune response against the ancestral strain, will that limit your ability then to make an immune response to a virus, which is very much different than the ancestral?”

Consider this scenario:

  • A person is  vaccinated against  the original Wuhan strain, and re-vaccinated multiple times against Wuhan.
  • That person receives a new vaccine targeting Omicron.
  • Will the immunological memory of the Wuhan strain hijack the response to the new, Omicron-specific vaccine, blocking the creation of antibodies against Omicron?

This occurrence is called original antigenic sin. It  occurs with some viruses, such as influenza and HPV. There are even instances of antibody-dependent-enhancement, ADE, when immunization makes a disease worse; this was noted for the original SARS. In depth: (ScienceDirect) The “original antigenic sin” and its relevance for SARS-CoV-2 (COVID-19) vaccination.

The reverse could also be true; repeated vaccination against the Wuhan strain could continue to enhance protection against all circulating strains for some time into the future.  Some encouraging data is found in (JAMA) Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection

Read the text, and look at this chart, which compares the antibody responses of breakthrough infections against 5 strains, Wuhan, Alpha, Beta, Gamma, and Delta. In every case, recipients of two doses of Pfizer had much stronger antibody responses than unvaccinated controls.

Omicron was not included in the study. But boosted recipients have good protection against Omicron.

In all the data so far, there is not a hint of “original antigenic sin”. Could it show up in the future? The Rubik’s Cube of COVID mutations holds many possibilities; the average person’s massive lifetime exposure to many coronaviruses works against it. OAS remains hypothetical.

When the  time comes, I’ll be getting that fourth shot.