Avian influenza is the most contagious disease not only in poultry, but also in humans. Avian influenza in humans occurs mainly in Southeast Asia, but no human-to-human pandemic has occurred. Meanwhile, outbreaks of a...Avian influenza is the most contagious disease not only in poultry, but also in humans. Avian influenza in humans occurs mainly in Southeast Asia, but no human-to-human pandemic has occurred. Meanwhile, outbreaks of avian influenza in poultry occur on a global scale and cause a large economic loss. Migration antibodies passed from mother birds via eggs are said to be an important component of the immune system that protects birds from infection. Thus, the immunity status of mother birds can determine the ability of offspring to defend against infection. In this study, we investigated the presence of anti-avian influenza virus antibody in chickens hatched on a poultry farm in Indonesia and examined the involvement of migratory antibodies in protecting against virus infection by infectious experiments of highly pathogenic avian influenza in chickens. Blood was collected from randomly selected chicks, and antibodies against avian influenza virus were evaluated in all birds. Since these young birds had no history of vaccination, the antibodies were deemed to have been transferred from the mother birds. The enzyme-linked immunosorbent assay antibody titer in each bird varied. Infection of these birds with highly pathogenic avian influenza virus A/H5N1 intra-nasally resulted in a high mortality rate in chicks with low antibody titers but a low mortality rate in chicks with high antibody titers. These findings indicate that migratory antibody prevented highly pathogenic avian influenza A/H5N1 infection in chicks, suggesting that such a preventive effect could also be expected with outdoor natural infection.展开更多
In this present study, we predicted the neutralizing epitope of a modeled H5N1 hemagglutinin 1046T when interacted with a modeled monoclonal antibody variable fragment 8H5Fv using molecular dynamics simulation. Follow...In this present study, we predicted the neutralizing epitope of a modeled H5N1 hemagglutinin 1046T when interacted with a modeled monoclonal antibody variable fragment 8H5Fv using molecular dynamics simulation. Following the production run of the molecular dynamics simulation, we observed the average change of solvent accessible surface of the antigen alongside the formation of hydrogen bonds between the two structures during the simulation. Based on the acquired data, we predicted the neutralizing epitope of the 1046T antigen to be consisted of residues Asp 84, Glu85, Phe86, Ile87, Asn88, Val89, Pro90, Ile132, Ser136, Val147, Pro152, Tyr153, Leu154, Arg161, and Tyr268. By calculating the RMSD of the Cα backbone chain of the complex during the simulation we found the structure to be generally stable suggesting a well maintained steric hindrance, while RMSD calculation of the predicted neutralizing epitope backbone suggests the stability of the neutralizing epitope itself.展开更多
Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of e...Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.展开更多
Human outbreaks of highly pathogenic avian influenza （HPAI） such as H5N1 and novel avian strains such as H7N9 have provoked significant public health concern. An outbreak of H5N1 in humans was first reported in Hon...Human outbreaks of highly pathogenic avian influenza （HPAI） such as H5N1 and novel avian strains such as H7N9 have provoked significant public health concern. An outbreak of H5N1 in humans was first reported in Hong Kong （HK）, China in 1997. This event was curtailed by a variety of public health measures including the culling of over 1.5 million chickens in the city.1 HSN1 has since re-emerged in multiple countries with over 600 reported infections and, since 2003, a case fatality of about 59% （World Health Organization （WHO） report, as of January 24, 2014）.展开更多
The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target f...The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.展开更多
Gastrointestinal(GI)cancers represent the leading cause of cancer-related mortality worldwide.Antibody drug conjugates(ADCs)are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient sur...Gastrointestinal(GI)cancers represent the leading cause of cancer-related mortality worldwide.Antibody drug conjugates(ADCs)are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient survival.ADCs combine tumour-antigen specific antibodies with cytotoxic drugs to deliver tumour cell specific chemotherapy.Currently,only two ADCs[brentuximab vedotin and trastuzumab emtansine(T-DM1)]have been Food and Drug Administration approved for the treatment of lymphoma and metastatic breast cancer,respectively.Clinical research evaluating ADCs in GI cancers has shown limited success.In this review,we will retrace the relevant clinical trials investigating ADCs in GI cancers,especially ADCs targeting human epidermal growth receptor 2,mesothelin,guanylyl cyclase C,carcinogenic antigen-related cell adhesion molecule 5(also known as CEACAM5)and other GI malignancy specific targets.We will review potential hurdles for their success and provide new perspective for future treatment.展开更多
Objectives This experiment used whole-cell patch-clamp technique to investigate the course of recovery from use- dependent block of Na ＋ channels （Nav 1.5） in human embryonic kidney （HEK） cells, on which to veri...Objectives This experiment used whole-cell patch-clamp technique to investigate the course of recovery from use- dependent block of Na ＋ channels （Nav 1.5） in human embryonic kidney （HEK） cells, on which to verify the effects of volatile oil of Nardostachy chinesis Batal （Gansong）. Methods Two pulses generated by computer followed by a recovery pulse and a test pulse, the interval duration between the two pulses varied from 16 ms to 1 s, and holding potential is -80 mV to - 140 inV. The peak Na^＋ current for a given recovery time was normalized to the tully recovered peak current, and the normalized value was the plot as a function of the recovery time to study the effects of 3 ppm concentration Gansong volatile oil on recovery from use-dependent block of Navl. 5 in HEK. Results It showed that Gansong group, comparing with control group, delayed the time courses of recovery from use-dependent block [ （33.2± 5.77 ） ms for control group and （52.5± 6.08 ） ms for 3 ppm Gansong group, P 〈 0.05 ] In the presence of Gansong, inhibition of the Na^＋ current was enhanced by increasing frequency of depolarizing pulse from 56.5 ms to 16 ms. In the control group, the time course of recovery showed that recovery started at 19.5 ms and finished by 36.5 ms. In the presence of Gansong, the time course of recovery showed that recovery started at 36.5 ms and finished by 56.5 ms. Na^＋ currents recovered from the use-dependent block varying with holding potential （holding potential-dependent）. Conclusions The results suggested that Na ＋ currents recovered from the use-dependent block correlated with persistent time, holding potential. The Gansong volatile oil has inhibitive effect on the Na^＋ current recovery.展开更多
文摘Avian influenza is the most contagious disease not only in poultry, but also in humans. Avian influenza in humans occurs mainly in Southeast Asia, but no human-to-human pandemic has occurred. Meanwhile, outbreaks of avian influenza in poultry occur on a global scale and cause a large economic loss. Migration antibodies passed from mother birds via eggs are said to be an important component of the immune system that protects birds from infection. Thus, the immunity status of mother birds can determine the ability of offspring to defend against infection. In this study, we investigated the presence of anti-avian influenza virus antibody in chickens hatched on a poultry farm in Indonesia and examined the involvement of migratory antibodies in protecting against virus infection by infectious experiments of highly pathogenic avian influenza in chickens. Blood was collected from randomly selected chicks, and antibodies against avian influenza virus were evaluated in all birds. Since these young birds had no history of vaccination, the antibodies were deemed to have been transferred from the mother birds. The enzyme-linked immunosorbent assay antibody titer in each bird varied. Infection of these birds with highly pathogenic avian influenza virus A/H5N1 intra-nasally resulted in a high mortality rate in chicks with low antibody titers but a low mortality rate in chicks with high antibody titers. These findings indicate that migratory antibody prevented highly pathogenic avian influenza A/H5N1 infection in chicks, suggesting that such a preventive effect could also be expected with outdoor natural infection.
文摘In this present study, we predicted the neutralizing epitope of a modeled H5N1 hemagglutinin 1046T when interacted with a modeled monoclonal antibody variable fragment 8H5Fv using molecular dynamics simulation. Following the production run of the molecular dynamics simulation, we observed the average change of solvent accessible surface of the antigen alongside the formation of hydrogen bonds between the two structures during the simulation. Based on the acquired data, we predicted the neutralizing epitope of the 1046T antigen to be consisted of residues Asp 84, Glu85, Phe86, Ile87, Asn88, Val89, Pro90, Ile132, Ser136, Val147, Pro152, Tyr153, Leu154, Arg161, and Tyr268. By calculating the RMSD of the Cα backbone chain of the complex during the simulation we found the structure to be generally stable suggesting a well maintained steric hindrance, while RMSD calculation of the predicted neutralizing epitope backbone suggests the stability of the neutralizing epitope itself.
基金supported by the General Program of the National Natural Science Foundation of China[No.31570162]the National Key Research Program[No.2016YFC1200200].
文摘Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
文摘Human outbreaks of highly pathogenic avian influenza （HPAI） such as H5N1 and novel avian strains such as H7N9 have provoked significant public health concern. An outbreak of H5N1 in humans was first reported in Hong Kong （HK）, China in 1997. This event was curtailed by a variety of public health measures including the culling of over 1.5 million chickens in the city.1 HSN1 has since re-emerged in multiple countries with over 600 reported infections and, since 2003, a case fatality of about 59% （World Health Organization （WHO） report, as of January 24, 2014）.
基金supported by the Natural Science Foundation of Guangdong (No. 2015A030313741)the National Natural Science Foundation of China (No. 31440041)+2 种基金Shenzhen Peacock Innovation Plan Fund (No. KQCX20140520154115029)Shenzhen Knowledge Innovation Program (No. JCYJ20140901003939 026)Novo Nordisk A/S-Chinese Academy of Sciences Research Fund (No. NNCAS-2013-9)
文摘The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.
文摘Gastrointestinal(GI)cancers represent the leading cause of cancer-related mortality worldwide.Antibody drug conjugates(ADCs)are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient survival.ADCs combine tumour-antigen specific antibodies with cytotoxic drugs to deliver tumour cell specific chemotherapy.Currently,only two ADCs[brentuximab vedotin and trastuzumab emtansine(T-DM1)]have been Food and Drug Administration approved for the treatment of lymphoma and metastatic breast cancer,respectively.Clinical research evaluating ADCs in GI cancers has shown limited success.In this review,we will retrace the relevant clinical trials investigating ADCs in GI cancers,especially ADCs targeting human epidermal growth receptor 2,mesothelin,guanylyl cyclase C,carcinogenic antigen-related cell adhesion molecule 5(also known as CEACAM5)and other GI malignancy specific targets.We will review potential hurdles for their success and provide new perspective for future treatment.
基金National Natural Science Foundation of People's Republic of China(No.30660060)
文摘Objectives This experiment used whole-cell patch-clamp technique to investigate the course of recovery from use- dependent block of Na ＋ channels （Nav 1.5） in human embryonic kidney （HEK） cells, on which to verify the effects of volatile oil of Nardostachy chinesis Batal （Gansong）. Methods Two pulses generated by computer followed by a recovery pulse and a test pulse, the interval duration between the two pulses varied from 16 ms to 1 s, and holding potential is -80 mV to - 140 inV. The peak Na^＋ current for a given recovery time was normalized to the tully recovered peak current, and the normalized value was the plot as a function of the recovery time to study the effects of 3 ppm concentration Gansong volatile oil on recovery from use-dependent block of Navl. 5 in HEK. Results It showed that Gansong group, comparing with control group, delayed the time courses of recovery from use-dependent block [ （33.2± 5.77 ） ms for control group and （52.5± 6.08 ） ms for 3 ppm Gansong group, P 〈 0.05 ] In the presence of Gansong, inhibition of the Na^＋ current was enhanced by increasing frequency of depolarizing pulse from 56.5 ms to 16 ms. In the control group, the time course of recovery showed that recovery started at 19.5 ms and finished by 36.5 ms. In the presence of Gansong, the time course of recovery showed that recovery started at 36.5 ms and finished by 56.5 ms. Na^＋ currents recovered from the use-dependent block varying with holding potential （holding potential-dependent）. Conclusions The results suggested that Na ＋ currents recovered from the use-dependent block correlated with persistent time, holding potential. The Gansong volatile oil has inhibitive effect on the Na^＋ current recovery.
