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Cell Rep
. 2026 Mar 6;45(3):117052.
doi: 10.1016/j.celrep.2026.117052. Online ahead of print.
Repeated COVID-19 vaccine boosters elicit variant-specific memory B cells in humans
M Alejandra Tortorici 1 , Kaitlin R Sprouse 2 , Amin Addetia 1 , Jack T Brown 1 , Jimin Lee 1 , Cameron Stewart 1 , Benjamin Merz 1 , Alex Harteloo 3 , Anna Elias-Warren 3 , Helen Y Chu 4 , David Veesler 5
Affiliations
The first exposure to a pathogen impacts subsequent immune responses toward related pathogens. This immune imprinting explains that infection or vaccination with circulating SARS-CoV-2 variants primarily recalls cross-reactive memory B cells induced by prior Wuhan-Hu-1 (Wu) spike (S) exposure. The magnitude and persistence of immune imprinting in mRNA vaccinees are not understood. We investigate serum antibody and memory B cell responses after administration of multiple XBB.1.5 and JN.1/KP.2 COVID-19 vaccine boosters. We find that the JN.1/KP.2 booster elicits broadly neutralizing antibody responses against recent SARS-CoV-2 variants by recalling Wu S-induced immunity in all but one individual. We detect an increased fraction of serum antibodies, and particularly memory B cells, recognizing XBB.1.5 and KP.2, but not Wu, relative to individuals who received a single XBB.1.5 booster. Repeated exposures to antigenically divergent S thus contribute to overcoming immune imprinting and support vaccine updates for continued protection.
Keywords: COVID-19 vaccines; CP: immunology; SARS-CoV-2 spike glycoprotein; antigenic sin; coronaviruses; immune imprinting; immunology; memory B cells; neutralizing antibodies; serum antibodies; virology.
. 2026 Mar 6;45(3):117052.
doi: 10.1016/j.celrep.2026.117052. Online ahead of print.
Repeated COVID-19 vaccine boosters elicit variant-specific memory B cells in humans
M Alejandra Tortorici 1 , Kaitlin R Sprouse 2 , Amin Addetia 1 , Jack T Brown 1 , Jimin Lee 1 , Cameron Stewart 1 , Benjamin Merz 1 , Alex Harteloo 3 , Anna Elias-Warren 3 , Helen Y Chu 4 , David Veesler 5
Affiliations
- PMID: 41800618
- DOI: 10.1016/j.celrep.2026.117052
The first exposure to a pathogen impacts subsequent immune responses toward related pathogens. This immune imprinting explains that infection or vaccination with circulating SARS-CoV-2 variants primarily recalls cross-reactive memory B cells induced by prior Wuhan-Hu-1 (Wu) spike (S) exposure. The magnitude and persistence of immune imprinting in mRNA vaccinees are not understood. We investigate serum antibody and memory B cell responses after administration of multiple XBB.1.5 and JN.1/KP.2 COVID-19 vaccine boosters. We find that the JN.1/KP.2 booster elicits broadly neutralizing antibody responses against recent SARS-CoV-2 variants by recalling Wu S-induced immunity in all but one individual. We detect an increased fraction of serum antibodies, and particularly memory B cells, recognizing XBB.1.5 and KP.2, but not Wu, relative to individuals who received a single XBB.1.5 booster. Repeated exposures to antigenically divergent S thus contribute to overcoming immune imprinting and support vaccine updates for continued protection.
Keywords: COVID-19 vaccines; CP: immunology; SARS-CoV-2 spike glycoprotein; antigenic sin; coronaviruses; immune imprinting; immunology; memory B cells; neutralizing antibodies; serum antibodies; virology.