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. 2022 Jan 6;185(3):457–466.e4. doi: 10.1016/j.cell.2021.12.033

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Additional mRNA vaccine dose (“booster”) induces potent neutralizing responses against SARS-CoV-2 Omicron variant that are low-to-absent in primary series (“non-boosted”) vaccinees

(A) Schematic representation of vaccinee cohorts of healthy adult community dwellers and healthcare workers. Participants who completed their primary series of vaccination with two-dose mRNA-1273 (Moderna), two-dose BNT162b (Pfizer), or 1-dose Ad26.COV2.S (Janssen) were included in this study. Vaccinees were stratified into four subgroups, as follows: infection-naive, non-boosted individuals that received primary vaccination series within last 3 months (“recent vax”); individuals that received primary vaccination series 6–12 months before and were either without (“distant vax”) or with a history or serologic evidence of SARS-CoV-2 infection (“distant vax + infection”); and infection-naive individuals that were boosted within the last 3 months (“booster vax”). History of SARS-CoV-2 infection was determined by either self-reported history of positive PCR test and/or positive anti-SARS-CoV-2 nucleocapsid antibody test.

(B) Schematic of experimental workflow of high-throughput SARS-CoV-2 pseudovirus neutralization assay used to determine neutralization titer of vaccinee sera against variants. Select images were created with BioRender.com.

(C) Neutralization titers (in WHO IU/mL) of wild-type (WT), Delta, and Omicron pseudoviruses were determined for people who received primary vaccination series with mRNA-1273 (top panel; in red), BNT162b2 (middle panel; in blue), or Ad26.COV2.S (bottom panel; in green) and classified into the aforementioned subgroups (in A). Dark horizontal lines for each group denote geometric mean titer. Pie charts show the proportion of vaccinees within each group that had detectable neutralization against the indicated SARS-CoV-2 pseudovirus. Fold-decrease in geometric mean neutralization titer of Omicron relative to wild type within a subgroup is shown as a number with “×” symbol within the gray region; this was done only for vaccinee subgroups where neutralization against wild-type pseudovirus was detected in 100% of individuals. All fold-decreases shown have unadjusted p < 0.05 with paired t test. Within “booster vax” subgroups (far right), boosters were homologous (same vaccine) except for 1 of 33 mRNA-1273 vaccinees that crossed-over to BNT162b (top panel; in blue), 6 of 30 BNT162b vaccinees that crossed-over to mRNA-1273 (middle panel; in red), and 7 of 8 Ad26.COV2.S vaccinees that crossed-over to mRNA-1273 (bottom panel; in red).