Well-Being Prevention & Cures

What is ‘hybrid immunity’ and why does it matter?

Story at a glance

  • Health officials are recommending third doses of the Pfizer/BioNTech vaccine for some people.
  • Experts are also thinking about how natural infection and vaccination may work together in the immune system.
  • A “hybrid immunity” from infection and vaccination could lead to a stronger immune response.

Health officials have recommended third doses of the Pfizer/BioNTech vaccine to people over 65, as well as those with health conditions or living in long term care facilities. The director of the Centers for Disease Control and Prevention (CDC) expanded to also recommend it for people in high risk jobs. Experts have also been talking about “hybrid immunity,” in which someone who was infected with the coronavirus later receives the vaccine. This combination seems to lead to a stronger immunity than with the vaccines alone.

A review published in the journal Science explains the theory of “hybrid vigor immunity” in which the combination of natural immunity and vaccine-generated immunity results in a “larger-than-expected immune response.” Hybrid vigor is a scientific concept in botany in which two plant lines are bred to create a stronger hybrid version because of the combination of genetic traits from the two parents.

For the concept of hybrid immunity, the combination would be of two types of stimulation to the immune system in the forms of natural infection and vaccination. The authors of the review suggest that this could happen with immunity because a broader range of immune cells, including both B and T cells, could get activated.

“With prior infection, their antibodies are able to recognize numerous variants, but with the addition of the vaccine, they are able to generate a large number to have a stronger effect against the virus,” Shane Crotty, one of the review authors and virologist at the La Jolla Institute for Immunology, told ABC News.


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In relation to the discussion about booster shots, some experts think there could be benefit to a delayed third dose.

“The best thing we can hope for is that three vaccine doses will emulate the super immune response, found among those previously infected with the virus,” said Paul Goepfert, an infectious disease physician and director of the Alabama Vaccine Research Clinic, to ABC News. “This [type of immunity] will protect against variants in the future.”

For hybrid immunity, timing seems to be an important factor.

“What we have seen is that waiting six months does mount a better immune response later,” Geopfert said to ABC News. “It seems that our immune system likes to rest and develop antibodies, and then mount a stronger response when it sees the same pathogen again later on.”


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