tetano
Editor, Senior Moderator
Vaccine
. 2025 Jul 4:62:127459.
doi: 10.1016/j.vaccine.2025.127459. Online ahead of print. Exposure to two antigenically distinct SARS-CoV-2 variants broadens neutralization patterns
Melanie M Schmitt[SUP] 1 [/SUP], Annika Rössler[SUP] 2 [/SUP], Antonia Netzl[SUP] 3 [/SUP], Ludwig Knabl[SUP] 4 [/SUP], Albert Falch[SUP] 1 [/SUP], Patrick Neckermann[SUP] 5 [/SUP], Marta Bermejo-Jambrina[SUP] 1 [/SUP], Wegene Borena[SUP] 1 [/SUP], Gagandeep Singh[SUP] 6 [/SUP], Florian Krammer[SUP] 7 [/SUP], Dorothee von Laer[SUP] 1 [/SUP], Ralf Wagner[SUP] 8 [/SUP], Derek J Smith[SUP] 3 [/SUP], Janine Kimpel[SUP] 9 [/SUP]
Affiliations
Previous exposure to one severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant influences neutralizing antibody responses induced by subsequent exposures. Consecutive exposures predominantly back-boost pre-existing immunity and expand cross-neutralizing antibodies while de novo variant-specific responses are poorly induced. In this study, we analyzed neutralizing antibodies against a panel of variants in plasma samples from individuals after exactly two exposures: twice pre-Omicron variant (either two dose vaccinated or infected and one dose vaccinated), pre-Omicron followed by early Omicron variant, or twice early Omicron variant. We found that exposure to two antigenically distinct variants, either pre-Omicron followed by Omicron or two different Omicron variants, increased the neutralization breadth. However, no significant cross-neutralization against the genetically closely related human coronavirus SARS-CoV was induced. Using depletion experiments, we showed that the first exposed variant strongly influences the specificity of antibodies. The second exposure primarily expanded cross-reactive antibodies rather than inducing a variant-specific response against the later variant, highlighting the phenomenon of immune imprinting in the context of SARS-CoV-2. Overall, our results indicate that multiple exposures to SARS-CoV-2 improve cross-neutralization against a variety of variants, but also underscore the lack of de novo antibody production against the more recently encountered variant.
Keywords: Cross-neutralization; Immune imprinting; Neutralizing antibodies; SARS-CoV-2.
. 2025 Jul 4:62:127459.
doi: 10.1016/j.vaccine.2025.127459. Online ahead of print. Exposure to two antigenically distinct SARS-CoV-2 variants broadens neutralization patterns
Melanie M Schmitt[SUP] 1 [/SUP], Annika Rössler[SUP] 2 [/SUP], Antonia Netzl[SUP] 3 [/SUP], Ludwig Knabl[SUP] 4 [/SUP], Albert Falch[SUP] 1 [/SUP], Patrick Neckermann[SUP] 5 [/SUP], Marta Bermejo-Jambrina[SUP] 1 [/SUP], Wegene Borena[SUP] 1 [/SUP], Gagandeep Singh[SUP] 6 [/SUP], Florian Krammer[SUP] 7 [/SUP], Dorothee von Laer[SUP] 1 [/SUP], Ralf Wagner[SUP] 8 [/SUP], Derek J Smith[SUP] 3 [/SUP], Janine Kimpel[SUP] 9 [/SUP]
Affiliations
- PMID: 40617091
- DOI: 10.1016/j.vaccine.2025.127459
Previous exposure to one severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant influences neutralizing antibody responses induced by subsequent exposures. Consecutive exposures predominantly back-boost pre-existing immunity and expand cross-neutralizing antibodies while de novo variant-specific responses are poorly induced. In this study, we analyzed neutralizing antibodies against a panel of variants in plasma samples from individuals after exactly two exposures: twice pre-Omicron variant (either two dose vaccinated or infected and one dose vaccinated), pre-Omicron followed by early Omicron variant, or twice early Omicron variant. We found that exposure to two antigenically distinct variants, either pre-Omicron followed by Omicron or two different Omicron variants, increased the neutralization breadth. However, no significant cross-neutralization against the genetically closely related human coronavirus SARS-CoV was induced. Using depletion experiments, we showed that the first exposed variant strongly influences the specificity of antibodies. The second exposure primarily expanded cross-reactive antibodies rather than inducing a variant-specific response against the later variant, highlighting the phenomenon of immune imprinting in the context of SARS-CoV-2. Overall, our results indicate that multiple exposures to SARS-CoV-2 improve cross-neutralization against a variety of variants, but also underscore the lack of de novo antibody production against the more recently encountered variant.
Keywords: Cross-neutralization; Immune imprinting; Neutralizing antibodies; SARS-CoV-2.