First SARS-CoV-2 vaccinations immune response to new virus variants

Immunological imprinting impacts human antibody reaction to SARS-CoV-2 mutations.


A new study from the Perelman School of Medicine at the University of Pennsylvania reveals that prior exposure to earlier SARS-CoV-2 vaccines strongly influences antibody responses to new variant infections and vaccinations.

The study, published in Immunity, examined antibody responses in people infected with or immunized against the BA.5 and XBB variations. The immune reactions mainly came from B cells previously triggered by vaccines against the ancestral strain, even though notable changes existed between these variations and the original strain.

The study indicates that booster shots against BA.5 and XBB variants effectively prevent severe illness, highlighting the enduring impact of initial viral exposure on immune responses to future variants.

Study co-senior author Scott Hensley, Ph.D., a professor of Microbiology at Penn Medicine, said, “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.”

E. John Wherry, MD, PhD, of Penn Medicine, also led the study. It was discovered that, despite their variations, antibodies to the novel strains BA.5 and XBB primarily targeted the original strain’s unaltered viral sites. This pattern held even after several exposures.

Certain antibodies were directed towards specific locations on the more altered XBB protein. Because B cells from the first viral exposure could cross-react with the new variations, the immune responses primarily depended on them. More original strain B cells allowed individuals to produce more potent immune responses against BA.5 and XBB.

When a person’s initial reaction to a virus influences subsequent reactions to related strains, this phenomenon is known as “immunological imprinting” or “original antigenic sin.” This has long been understood, particularly about influenza viruses. There is concern that among those exposed to prior strains, it may impede their immune responses to more recent strains. Because SARS-CoV-2 is constantly evolving, scientists are examining how imprinting influences how the virus reacts to its variations.

In this study, researchers examined the effects of imprinting on antibody responses to the SARS-CoV-2 variants BA.5 and XBB. These 2022-emerging versions differ significantly from the original virus. Later on, booster injections were added for these variations.

Hensley said that “having previous vaccines is really beneficial. They aid in developing memory B cells, which produce antibodies against novel SARS-CoV-2 variants fast.”

The study suggests that previous exposure to the original SARS-CoV-2 strain affects how our bodies respond to BA.5 and XBB variants and their boosters. While these responses still protect us, it’s unclear if this protection will remain strong as new variants emerge. Therefore, researchers advise ongoing monitoring of immune imprinting’s impact on SARS-CoV-2 responses through further studies.

Journal reference:

  1. Timothy S. Johnston, Shuk Hang Li, et al., Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants. Immunity. DOI: 10.1016/j.immuni.2024.02.017.