Abstract
Since the 2017 Southern Hemisphere influenza season, the A(H1N1)pdm09-like virus recommended for use in the vaccine was changed because human, but not ferret, sera distinguish A(H1N1)pdm09 viruses isolated after 2013 from the previously circulating strains. An amino acid substitution, lysine to glutamine, at position 166 (H3 numbering) in the major antigenic site of HA was reported to be responsible for the antigenic drift. Here, we obtained two anti-A(H1N1)pdm09 HA monoclonal antibodies that failed to neutralize viruses isolated after 2013 from a vaccinated volunteer. Escape mutations were identified at position 129, 165, or 166 in the major antigenic site of HA. Competitive growth of the escape mutant viruses with the wild-type virus revealed that some escape mutants possessing an amino acid substitution other than K166Q showed superior growth to that of the wild-type virus. These results suggest that in addition to the K166Q mutation that occurred in epidemic strains, other HA mutations can confer resistance to antibodies that recognize the K166 area, leading to emergence of epidemic strains with such mutations.
Highlights
The first influenza pandemic of the 21st century began in 2009 with the emergence of the A(H1N1)pdm[09] virus, which replaced the previous seasonal H1N1 virus[1,2]
In vitro selection of escape mutants from these monoclonal antibodies revealed that a mutation at position 166 of HA was responsible for the resistance to neutralization, suggesting that the antigenic drift was caused by the selective pressure of the human antibodies recognizing the epitope around position 16617
An antigenic variant with the HA-K166Q mutation was selected in nature and became an epidemic strain in the 2012–2013 season, A(H1N1)pdm[09] viruses possessing the N129D or S165N mutation temporarily appeared in the 2010–2011 season[20,21]
Summary
The first influenza pandemic of the 21st century began in 2009 with the emergence of the A(H1N1)pdm[09] virus, which replaced the previous seasonal H1N1 (sH1N1) virus[1,2]. Middle-aged adults (i.e., born between 1965 and 1979) were reported to have a high antibody titer against the epitope around position 166 of the HA of A(H1N1)pdm[09] viruses that were circulating before 2012, since they had been exposed to sH1N1 viruses that were circulating before 1985 and whose HA lacked the 129-NHT-131 glycosylation site These middle-aged adults suffered from A(H1N)pdm[09] virus infection with substantial morbidity and mortality during the 2013–2014 influenza season because of low neutralization antibody titers against the viruses possessing the K166Q substitution[12]. These reports demonstrate that the epitope around position 166 plays a role in the antigenic drift recently detected in assays with human, but not ferret, sera. We attempted to obtain escape mutants possessing an amino acid substitution other than at position 166 and compared their growth ability with that of the wild-type virus
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