Recommendations for vaccine strain updates and the influenza A H3N2 and pH1N1 strains to be used for the human influenza vaccine, according to the method described in Klingen, Reimering et al., which performed favorable in comparison to the recommendations of the WHO in retrospective testing experiments. All data of the study as well as the software are available here.
We provide the recommendations with our method in parallel to the WHO, using a computational approach. In short, the SD plots method utilizes all available genetic sequences of the major surface protein of circulating influenza A viruses. From available sequences from the EpiFlu database, a genealogy is calculated for each subtype, and the changes in frequencies of amino acid changes associated with a particular clade are determined. Changes increasing significantly in frequency among the sequenced isolates over consecutive seaons are considered as candidate changes providing a selective advantage. If these changes have reached a frequency of more than 50% in the current season and are located in antigenicity-altering regions of the surface protein, an update of the vaccine strain with a strain from the particular clade is recommended. There is no consideration of antigenic or neutralization data from the current season, as this is not made (publicly) available by the WHO. Note that analysis of clade-associated amino acid change dynamics is different from counting frequencies of amino acid changes from the raw data. The latter approach cannot distinguish between homoeoplasies, i.e. amino acid changes introduced multiple times in parallel in the evolutionary history, and thus of the genetic context of changes, or consider changes that have later been reverted again.
| Current season | Season recommended | Date of recommendation | Recommended H3N2 vaccine strain | Recommended pH1N1 vaccine strain |
|---|---|---|---|---|
| 2017S | 2018S | 19 September 2017 | A/Singapore/INFIMH-16-0019/2016 | A/Michigan/45/2015 |
| 2018N | 2019N | 22 February 2018 | A/Singapore/INFIMH-16-0019/2016 | A/Michigan/45/2015 |
| 2018S | 2019S | 27 September 2018 | A/Switzerland/8060/2017 | A/Michigan/45/2015 |
| 2019N | 2020N | 21 February 2019 (updated on 21 March 2019) | A/Kansas/14/2017 | A/Brisbane/02/2018 |
| 2019S | 2020S | 27 September 2019 | A/South Australia/34/2019 | A/Brisbane/02/2018 |
| 2020N | 2021N | 28 February 2020 | A/Hong Kong/2671/2019 | A/Guangdong-Maonan/SWL1536/2019 (Egg-based vaccine) |
| 2020S | 2021S | 25 September 2020 | A/Hong Kong/2671/2019 | A/Victoria/2570/2019 (Egg-based vaccine) |
Information about current vaccine strains is obtained from the WHO and the Francis Crick Institut.
*The antigenicity and avidity changing sites that we use for the evaluation have been experimentally identified for the H3N2 subtype and don't necessarily have the same function in the pH1N1 virus. To our knowledge, there are no comprehensive studies of antigenicity or avidity altering sites in the pH1N1 virus yet, which makes the evaluation of observed sites in the SD plots difficult for this subtype and the recommendation should be taken with caution.
Comparison of predominant antigenic types for human influenza A/H3N2, predictions using SD plots and recommendations made by the WHO. The selection of a vaccine strain takes place two seasons before the vaccine is available. Any prediction of newly arising antigenically novel strains should therefore be compared to the predominant antigenic type two seasons later (indicated by diagonal lines in plot). First row: colored boxes indicate the predominant antigenic variant and additional colored borders indicate different dominantly circulating strains matching the same antigenic variant. Second row: for the SD plots analysis, seasons are marked with an X, if sweep-related changes distinguish the respective vaccine strain from the previous one. Seasons with sweep-changes not associated with antigenicity-altering or avidity-changing sites are marked in grey. Third row: sweep-related changes in antigenicity or avidity changing sites. Using these as a criterion for vaccine strain updates, results in a simultaneous or earlier detection of newly emerging antigenic types than with the procedure utilized by the WHO. Fourth row: detected sweep-related sites neither known to change the avidity or the antigenicity. Fifth row: WHO recommendations. Until 2017N, performance was evaluated in retrospective testing, where data from after the time of the WHO vaccine strain meeting for a particular season was excluded from the analysis. From 2017S onwards, predictions were made for the future and can be monitored live at https://github.com/hzi-bifo/SDplots_VaccineUpdates (marked in Figure above).