CDC performs genetic and antigenic characterization of U.S. viruses submitted from state and local health laboratories using Right Size Roadmap submission guidance. These data are used to compare how similar the currently circulating influenza viruses are to the reference viruses used for developing new influenza vaccines and to monitor evolutionary changes that continually occur in circulating influenza viruses. Antigenic characterization data are based on an animal model (influenza-naive ferrets), and do not reflect pre-existing protection provided by past influenza infections and vaccinations. Additional antigenic characterization studies involving people vaccinated with current influenza vaccines are conducted later in the season; these data account for pre-existing protection in different populations against circulating influenza viruses. Genetic and antigenic characterization data are not used to make calculations about vaccine effectiveness (VE). CDC conducts VE studies each year to measure the benefits of flu vaccines in people. Interim estimates of 2019-2020 flu vaccine effectiveness have been released.

CDC genetically characterized 2,463 influenza viruses collected in the U.S. from September 29, 2019, to April 4, 2020.

Influenza Virus Characterization from viruses collected in the U.S. from September 29, 2019 Virus Subtype or Lineage Genetic Characterization Total No. of

Subtype/Lineage

Tested Clade Number (% of

subtype/lineage

tested) Subclade Number (% of

subtype/lineage

tested) A/H1 896 6B.1A 896 (100%) A/H3 510 3C.2a 480 (94.1%) 2a1 480 (94.1%) 2a2 0 2a3 0 2a4 0 3C.3a 31 (5.9%) 3a 31 (5.9%) B/Victoria 965 V1A 965 (100%) V1A 0 V1A.1 60 (6.2%) V1A.3 905 (93.8%) B/Yamagata 92 Y3 92 (100%)

CDC antigenically characterizes a subset of influenza viruses by hemagglutination inhibition (HI) or neutralization based Focus Reduction assays (FRA). Antigenic drift is evaluated by comparing antigenic properties of cell-propagated reference viruses representing currently recommended vaccine components with those of cell-propagated circulating viruses. CDC antigenically characterized 547 influenza viruses collected in the United States from September 29, 2019, to April 4, 2020. These data are not used to make calculations about vaccine effectiveness (VE). CDC conducts VE studies each year to measure the benefits of flu vaccines in people.

Influenza A Viruses

A (H1N1)pdm09: 212 A(H1N1)pdm09 viruses were antigenically characterized by HI with ferret antisera, and 175 (82.5%) were antigenically similar (reacting at titers that were within 4-fold of the homologous virus titer) to cell-propagated A/Brisbane/02/2018-like reference viruses representing the A(H1N1)pdm09 component for the 2019-20 Northern Hemisphere influenza vaccines. The decrease in the percent of A(H1N1)pdm09 viruses similar to A/Brisbane/02/2018 is due to some of the recent viruses selected for testing having a single amino acid change that is antigenically distinguishable in antigenic assays using ferret sera. Similar viruses were observed last season as well and these represented a small proportion of virus circulating. We have observed an increase in the proportion of H1N1pdm09 viruses with this change late in the US season.

212 A(H1N1)pdm09 viruses were antigenically characterized by HI with ferret antisera, and 175 (82.5%) were antigenically similar (reacting at titers that were within 4-fold of the homologous virus titer) to cell-propagated A/Brisbane/02/2018-like reference viruses representing the A(H1N1)pdm09 component for the 2019-20 Northern Hemisphere influenza vaccines. The decrease in the percent of A(H1N1)pdm09 viruses similar to A/Brisbane/02/2018 is due to some of the recent viruses selected for testing having a single amino acid change that is antigenically distinguishable in antigenic assays using ferret sera. Similar viruses were observed last season as well and these represented a small proportion of virus circulating. We have observed an increase in the proportion of H1N1pdm09 viruses with this change late in the US season. A (H3N2): 86 A(H3N2) viruses were antigenically characterized by FRA with ferret antisera, and 40 (46.5%) were antigenically similar to cell-propagated A/Kansas/14/2017-like reference viruses representing the A(H3N2) component for the 2019-20 Northern Hemisphere influenza vaccines.

Influenza B Viruses

B/Victoria: 201 B/Victoria lineage viruses, including viruses from both co-circulating sub-clades, were antigenically characterized by HI with ferret antisera, and 120 (59.7%) were antigenically similar to cell-propagated B/Colorado/06/2017-like reference viruses representing the B/Victoria component for the 2019-20 Northern Hemisphere influenza vaccines.

201 B/Victoria lineage viruses, including viruses from both co-circulating sub-clades, were antigenically characterized by HI with ferret antisera, and 120 (59.7%) were antigenically similar to cell-propagated B/Colorado/06/2017-like reference viruses representing the B/Victoria component for the 2019-20 Northern Hemisphere influenza vaccines. B/Yamagata: 48 B/Yamagata lineage viruses were antigenically characterized by HI with ferret antisera, and all 48 (100%) were antigenically similar to cell-propagated B/Phuket/3073/2013-like reference viruses representing the B/Yamagata component for the 2019-20 Northern Hemisphere influenza vaccines.

CDC also assesses susceptibility of influenza viruses to the antiviral medications including the neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir) and the PA endonuclease inhibitor baloxavir using next generation sequence analysis supplemented by laboratory assays. Viruses collected in the United States since September 29, 2019, were tested for antiviral susceptibility as follows:

susceptibility of influenza viruses to the antiviral medications Antiviral Medication Total

Viruses* A/H1 A/H3 B/Victoria B/Yamagata Neuraminidase

Inhibitors Oseltamivir Viruses

Tested 2,433 885 502 954 92 Reduced

Inhibition 1 (0.04%) (0.0%) (0.0%) 1 (0.1%) (0.0%) Highly

Reduced

Inhibition 4 (0.2%) 4 (0.5%) (0.0%) (0.0%) (0.0%) Peramivir Viruses

Tested 2,433 885 502 954 92 Reduced

Inhibition (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) Highly

Reduced

Inhibition 5 (0.2%) 4 (0.5%) (0.0%) 1 (0.1%) (0.0%) Zanamivir Viruses

Tested 2,433 885 502 954 92 Reduced

Inhibition 2 (0.1%) (0.0%) (0.0%) 2 (0.2%) (0.0%) Highly

Reduced

Inhibition (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) PA Endonuclease Inhibitor Baloxavir Viruses

Tested 2,541 884 584 978 95 Reduced

Susceptibility (0.0%) (0.0%) (0.0%) (0.0%) (0.0%)

* Six influenza viruses showed reduced or highly reduced inhibition by at least one neuraminidase inhibitor. Four A(H1N1)pdm09 viruses showed highly reduced inhibition to oseltamivir and peramivir while showing normal inhibition to zanamivir. In addition, one B/Victoria virus showed highly reduced inhibition to peramivir and reduced inhibition to oseltamivir and zanamivir, while another influenza B/Victoria virus showed reduced inhibition to zanamivir.

A total of 556 additional viruses (211 A(H1N1)pdm09, 32 A(H3N2), and 313 B) collected in Alabama, Alaska, Florida, Illinois, Iowa, Louisiana, Massachusetts, Michigan, Nevada, New York, North Carolina, Pennsylvania, South Dakota, Virginia and Wisconsin were analyzed for resistance to neuraminidase inhibitors by pyrosequencing assay. Three (1.4%) of the 211 A(H1N1)pdm09 viruses tested had the H275Y amino acid substitution in the neuraminidase and showed highly reduced inhibition by oseltamivir and peramivir. No molecular markers associated with reduced or highly reduced inhibition by neuraminidase inhibitors were detected in A(H3N2) and type B viruses tested.