A deterministic model for homologous antibody dependant enhancement on influenza infection

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 population level,antibody dependant enhancement can promote H1N1 and H3N2 influenza virus cooperate to sustain long-term circulation on human populations according to antigenic seniority theory.

Genomic similarity and antibody-dependent enhancement of immune serum potentially affect the protective efficacy of commercial MLV vaccines against NADC30-like PRRSV

Porcine reproductive and respiratory syndrome(PRRS)is one of the most significant diseases affecting the pig industry worldwide.The PRRSV mutation rate is the highest among the RNA viruses.To date,NADC30-like PRRSV and highly pathogenic PRRSV(HP-PRRSV)are the dominant epidemic strains in China;however,commercial vaccines do not always provide sufficient cross-protection,and the reasons for insufficient protection are unclear.This study isolated a wild-type NADC30-like PRRSV,SX-YL1806,from Shaanxi Province.Vaccination challenge experiments in piglets showed that commercial modified live virus(MLV)vaccines provided good protection against HP-PRRSV.However,it could not provide sufficient protection against the novel strain SXYL1806.To explore the reasons for this phenomenon,we compared the genomic homology between the MLV strain and HP-PRRSV or NADC30-like PRRSV and found that the MLV strain had a lower genome similarity with NADC30-like PRRSV.Serum neutralization assay showed that MLV-immune serum slightly promoted the homologous HP-PRRSV replication and significantly promoted the heterologous NADC30-like PRRSV strain replication in vitro,suggesting that antibody-dependent enhancement(ADE)might also play a role in decreasing MLV protective efficacy.These findings expand our understanding of the potential factors affecting the protective effect of PRRSV MLV vaccines against the NADC30-like strains.

Seroepidemiologic study on convalescent sera from dengue fever patients in Jinghong,Yunnan

After dengue virus(DENV)infection,antibody-dependent enhancement(ADE)is easy to occur when the neutralizing antibody(NAb)gradually decreases to a sub-neutralizing concentration.In this cohort surveillance,we utilized sera samples collected from dengue fever patients at different convalescent phases in Jinghong City,to investigate the dynamic change rule of DENV-specific antibodies,and to analyze the risk of ADE caused by secondary infection with heterologous serotypes DENVs.For baseline serosurvey,191 four-year and 99 six-year sera samples during convalescence were collected in 2017 and 2019,respectively.The positive rate of DENVspecific immunoglobulin G was 98.4%in 2017,which significantly decreased to 82.8%in 2019.The geometric mean titer(GMT)of NAb decreased from 1:155.35 to 1:46.66.Among 290 overall samples,73 paired consecutive samples were used for follow-up serosurvey.In four-year sera,the GMTs of NAb against DENV-3 and cross-reactive antibodies against DENV-1,DENV-2 and DENV-4 were 1:167.70,1:13.80,1:18.54 and 1:45.26,respectively,which decreased to 1:53.18,1:10.30,1:14.60 and 1:8.17 in six-year sera.In age-stratified analysis,due to the increasing number of ADE positive samples from 2017 to 2019 in 31–40 and 51–60 years groups,the risk of ADE in DENV-4 infection was positively associated with the extension of convalescent phase,and the odd ratio was higher than other groups.With the recovery period lengthened,the risk of secondary infection with DENV-1 and DENV-2 was reduced.Our results offer essential experimental data for risk prediction of severe dengue in hyper-endemic dengue areas,and provide crucial scientific insight for the development of effective dengue vaccines.