INTRODUCTION
In 2009 a new H1N1 influenza A virus emerged in Mexico and spread quickly through the global human population, thereby causing the first influenza pandemic of the 21st century and the seasonal A(H1N1) viruses circulating previously have since been replaced by this pandemic A(H1N1)pdm09 strain (1-3). With respect to their antigenic properties, A(H1N1)pdm09 viruses have remained closely related to the first viruses that emerged in 2009 ; the initial vaccine virus A/California/7/2009 was replaced only twice: in season 2017-2018 by Michigan/45/2015 and in season 2019-2020 by Brisbane/02/2018 (https://www.who.int/influenza/vaccines/virus/recommendations/en/ ). A high level of antigenic reactivity remained between circulating viruses and antisera to the initial vaccine virus of 2009 (https://www.crick.ac.uk/sites/default/files/2018-07/crick_nh_vcm_report_feb_2017_v2.pdf). Accordingly, the hemagglutinin (HA) of A(H1N1)pdm09 viruses is similar to that of 1918 pandemic influenza A(H1N1) viruses (4): While it lacks the multiple N-glycosylation sites that were associated with antigenic drift of the previous seasonal A(H1N1) viruses, it retains codon-motifs that are able to become N-glycosylated (5). Therefore it is deemed probable that antigenic drift of A(H1N1)pdm09 viruses will occur in the near future (5). A(H1N1)pdm09 viruses are strong antigens in humans and therefore vaccine effectiveness achieved by the A(H1N1)pdm09 viruses is superior to that observed for A(H3N2) influenza viruses (6, 7). Here, we report the emergence of antigenic drift variants that may be the first signs of the predicted antigenic evolution of A(H1N1)pdm09 viruses. Antigenic drift may have substantial clinical and therapeutic implications, as has been exemplified by the drift of the previous A(H1N1) seasonal viruses, which led to neuraminidase inhibitor resistance during the last years of their circulation in the human population (8, 9). Thus, continued surveillance of A(H1N1)pdm09 viruses is of major importance.