A deterministic model for homologous antibody dependant enhancement on influenza infection  

作　　者：Shilian Xu Jiaru Yang 

机构地区：[1]Department of Environment and Genetics,School of Agriculture,Biomedicine and Environment,La Trobe University,Bundoora,VIC,3086,Australia [2]Department of Mathematical and Physical Sciences,La Trobe University,Bundoora,VIC,3086,Australia [3]Department of Biochemistry and Molecular Biology,Biomedicine Discovery Institute,Monash University,Clayton,VIC,3800,Australia [4]The Institute for Tropical Medicine,School of Basic Medical Sciences,Kunming Medical University,Kunming,650500,China

出　　处：《Infectious Disease Modelling》2024年第4期1265-1275,共11页传染病建模（英文）

摘　　要：Antibody dependant enhancement refers that viral infectivity was unexpectedly enhanced at low antibody concentration compared to when antibodies were absent,such as Dengue,Zika and influenza virus.To mathematically describe switch from enhancement to neutralisation with increase of antibody concentration,one hyperbolic tangent variant is used as switching function in existed models.However,switching function with hyperbolic tangent contains four parameters,and does not always increase with antibody concentration.To address this problem,we proposed a monotonically increasing Logistical function variant as switching function,which only contains position parameter and magnitude parameter.Analysing influenza viral titre estimated from 21 focus reduction assay(FRA)datasets from neutralisation group(viral titre lower than negative control on all serial dilutions)and 20 FRA dataset from enhancement group(viral titre higher than negative control on high serial dilution),switching function with Logistic function performs better than existed model independent of both groups and exhibited different behaviour/character;specifically,magnitude parameter estimated from enhancement group is lower,but position parameter estimated from enhancement group is higher.A lower magnitude parameter refers that enhancement group more rapidly switches from enhancement to neutralisation with increase of antibody concentration,and a higher position parameter indicates that enhancement group provides a larger antibody concentration interval corresponding to enhancement.Integrating estimated neutralisation kinetics with viral replication,we demonstrated that antibody-induced bistable influenza kinetics exist independent of both groups.However,comparing with neutralisation group,enhancement group provides higher threshold value of antibody concentration corresponding to influenza infectivity.This explains the observed phenomenon that antibody dependent enhancement enhances susceptibility,severity,and mortality to influenza infection.On populatio

关 键 词：Antibody dependent enhancement Logistical function Switching function Influenza virus 

分 类 号：R511.7[医药卫生—内科学]