Initial SARS-CoV-2 vaccinations prime immune cells to respond to subsequent variants

Immunological imprinting from the original ancestral SARS-CoV-2 strain has a significant impact on the antibody responses to the variants and boosters based on them.

Antibody responses to new SARS-CoV-2 variant infections and vaccinations are powerfully shaped by prior exposures to earlier SARS-CoV-2 vaccines, according to a new study from the Perelman School of Medicine.

A person wearing latex gloves using a pipette and a microscope in a lab.
Image: iStock/Thicha Satapitanon

In the study, published in Immunity, co-senior authors Scott Hensley and E. John Wherry analyzed antibody responses in people infected with or vaccinated against the relatively new SARS-CoV-2 variants BA.5 and XBB. They found that even though BA.5 and XBB are very different from the original “ancestral” version of SARS-CoV-2, the responses to these newer variants came almost entirely from the B cell repertoire that was already in place due to prior vaccinations against the ancestral strain.

These responses efficiently prevented BA.5 and XBB variants from infecting cells, which likely explains why BA.5 and XBB boosters protect recipients against severe illness from these new variants. Yet the findings underscore the power of an initial viral exposure, like from the initial SARS-CoV-2 vaccines, to shape immune responses to new variants even years later.

“Detailing how SARS-CoV-2 immune history influences the antibody response to new variants, through studies such as this one, will ultimately help us design more effective vaccines,” says Hensley, a professor of microbiology at Penn Medicine.

The phenomenon in which an initial antibody response to a virus dominates and delimits the response to later strains of the same virus is called “immunological imprinting,” or “original antigenic sin.” Given the striking ability of SARS-CoV-2 to evolve new variants, researchers have begun to detail imprinting’s effects in the SARS-CoV-2 context.

In the study, the researchers examined imprinting’s effects on antibody responses to SARS-CoV-2’s BA.5 and XBB variants. “Prior vaccinations are highly beneficial for establishing memory B cells that can be rapidly recruited to produce neutralizing antibodies against new SARS-CoV-2 variants,” Hensley says.

The main implication of the findings, according to the researchers, is that immunological imprinting from the original ancestral SARS-CoV-2 strain has a significant impact on the antibody responses to the BA.5 and XBB variants and boosters based on them.

Read more at Penn Medicine News.