Antigenic Drift of the Hemagglutinin from an Influenza A(H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro

The influenza A(H1 N1)pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years.Here,we analyzed a clinical influenza A(H1 N1)pdm09-infected patient case hospitalized for two months in Guangdong(from December 14,2019 to February 15,2020).This isolate,named A/Guangdong/LCF/2019(LCF/19),was genetically sequenced,rescued by reverse genetics,and phylogenetically analyzed in the context of other relevant pdm09 isolates.Compared with earlier isolates,this pdm09 virus’s genetic sequence contains four substitutions,S186 P,T188 I,D190 A,and Q192 E,of the hemagglutinin(HA)segment at position 186–192(H3 numbering)in the epitope Sb,and two of which are located at the 190-helix.Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in2018.To characterize the pathogenicity of this novel substitution motif,a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued.Kinetic growth data revealed that the reassortant viruses,including the LCF/2019 with the PTIAAQE substitution,propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney(MDCK)cells.The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018,suggesting that old vaccines might not effectively protect people from infection.Due to the difference in the selection of vaccine strains,people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.

Relatively rapid evolution rates of SARS-CoV-2 spike gene at the primary stage of massive vaccination

A series of stringent non-pharmacological and pharmacological interventions were implemented to contain the pandemic but the pandemic continues.Moreover,vaccination breakthrough infection and reinfection in convalescent coronavirus disease 2019(COVID-19)cases have been reported.Further,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants emerged with mutations in spike(S)gene,the target of most current vaccines.Importantly,the mutations exhibit a trend of immune escape from the vaccination.Herein the scientific question that if the vaccination drives genetic or antigenic drifts of SARS-CoV-2 remains elusive.We performed correlation analyses to uncover the impacts of wide vaccination on epidemiological characteristics of COVID-19.In addition,we investigated the evolutionary dynamics and genetic diversity of SARS-CoV-2 under immune pressure by utilizing the Bayesian phylodynamic inferences and the lineage entropy calculation respectively.We found that vaccination coverage was negatively related to the infections,severe cases,and deaths of COVID-19 respectively.With the increasing vaccination coverage,the lineage diversity of SARS-CoV-2 dampened,but the rapid mutation rates of the S gene were identified,and the vaccination could be one of the explanations for driving mutations in S gene.Moreover,new epidemics resurged in several countries with high vaccination coverage,questioning their current pandemic control strategies.Hence,integrated vaccination and non-pharmacological interventions are critical to control the pandemic.Furthermore,novel vaccine preparation should enhance its capabilities to curb both disease severity and infection possibility.