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seasonal A(H1N1) viruses circulating previously have since been replaced
by this pandemic A(H1N1)pdm09 strain (1-3).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.