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. 2021 Mar 2;11:4554. doi: 10.1038/s41598-020-79590-7

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Next-generation H3 COBRA HA multi-consensus sequence layering approach scenarios and final antigen designs. Secondary layer consensus sequences derived from influenza isolates spanning a 2.5 year period are used to generate a “backbone” consensus sequence (light grey bar). (a) Scenario 1. Secondary consensus sequences produced from the most recent 6-months of A(H3N2) influenza circulation are added into the backbone sequences, and secondary sequences from the oldest 6-month season of the 3-year period are dropped off. This process is repeated for each 6-month period of the design era. (b) Scenario 2. Secondary sequences produced from the most recent 6-months of influenza circulation are added to the “backbone” sequence and the oldest sequences from the design era are retained. This process is repeated for each 6-month period of the design era. (c) Description of the next-generation COBRA H3 HA vaccine antigens, their design eras, and the scenario used to generate them. TJ1–4 were designed utilizing wild-type influenza virus HA sequences from 2002 to 2007, and TJ5–9 were generated from HA input sequences that were in circulation from 2008 to 2015.