Rabies Virus Neutralizing Activity,Safety,and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults

Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Methods Subjects were randomly(1:1:1)allocated to Groups A(20 IU/kg NM57),B(40 IU/kg NM57),or C(20 IU/kg HRIG).One injection was given on the day of enrollment.Blood samples were collected on days-7 to 0(pre-injection),3,7,14,28,and 42.Adverse events(AEs)and serious AEs(SAEs)were recorded over a period of 42 days after injection.Results All 60 subjects developed detectable rabies virus neutralizing antibodies(RVNAs)(>0.05 IU/mL)on days 3,7,14,28,and 42.The RVNA levels peaked on day 3 in all three groups,with a geometric mean concentration(GMC)of 0.2139 IU/mL in Group A,0.3660 IU/mL in Group B,and0.1994 IU/mL in Group C.At each follow-up point,the GMC in Group B was significantly higher than that in Groups A and C.The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C.Fifteen AEs were reported.Except for one grade 2 myalgia in Group C,the other 14 were all grade 1.No SAEs were observed.Conclusion The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG,and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar.Safety was comparable between NM57 and HRIG.

Establishment of a Chinese street rabies virus library and its application for detecting neutralizing activity

Background:The injection of rabies immune globulin(RIG)is of the utmost importance in the management of category III exposures to rabies-suspect animals.Because of the high cost and limited availability of existing RIG,one possible replacement for RIG is monoclonal antibodies(MAbs)against the rabies virus(RABV).Consequently,it is necessary to determine the neutralizing activity of the MAbs against rabies viruses,especially street rabies virus.However,the method to detect the neutralizing activity of MAbs against street rabies virus remains undefined.Methods:To establish a method for detecting the neutralizing activity of MAbs against street rabies virus,we constructed a library consisting of 12 strains of street RABV from 11 provinces in China.Using this street RABV library and the Reed-Muench formula,we established a method for detecting the neutralizing titer of the MAbs.The reliability and repeatability of the method were evaluated by repeatedly measuring the neutralizing activity of a MAb and a post vaccination serum.Results:A total of 12 strains of street RABV were chosen for inclusion in the street RABV library,which covered six Chinese lineages(China I-China VI)and grew to high titers in N2A cells(>105 FFD50/ml).On the basis of the library,we constructed the method to detect the neutralizing activity of the MAbs.The results of repeatedly measuring the MAbs and positive serum showed excellent reliability and repeatability of the method established in this study.Conclusions:This study established a street RABV library reflecting the epidemiological features of Chinese rabies viruses,which provides a platform for detecting the neutralizing activity of MAbs against rabies viruses circulating in China.

A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9

Background:The new emerging avian influenza A H7N9 virus,causing severe human infection with a mortality rate of around 41%.This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin(HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province,China.The human monoclonal antibodies(mAbs)were generated by amplification and cloning of these HA-specific B cells.First,all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay.Then,those mAbs,exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting(HAI)and microneutralizationin vitro assays.Finally,the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes,including H1N1 and H3N2.The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50(TCID_(50))of H7N9 virus(influenza A/Nanjing/1/2013)invitro,with neutralizing activity as low as 78 ng/mL.In addition,the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

Neutralization activity of influenza A virus humanized antibodies against new subtypes of influenza viruses

Antibodies are ideal for controlling the influenza A virus,but their effect on newly emerging strains is unclear.Here,we assessed the neutralization activity of the humanized monoclonal antibodies(mAbs)F10,H98 and H40 against circulating influenza viruses(H5N1,H1N1,H3N2 and H7N7 and new subtypes viruses H5N6 and H7N9).The results showed that all the three humanized mAbs(F10,H98 and H40)displayed different degrees of virus neutralization activities when encountered with different subtypes of influenza viruses.Remarkably,the humanized monoclonal antibody F10 produced higher and broader neutralization titers(range 25–1.56μg/ml)than those of the other two humanized mAbs(H98(range 50–3.12μg/ml),H40(range 50–5.56μg/ml))to against the viruses H5N1,H1N1,H3N2,H7N7,H5N6 and H7N9.This mAb may represent a new class of heterosubtypic neutralizing humanized mAb that could replace vaccines and chemical drugs.

Palladium-catalyzed allylation of active methylene compounds with allyl perfluoroalkanoates under neutral conditions

Palladium-catalyzed allylation of carbonucleophiles has been widely used for carbon-carbon bond formation.Among the allylic compounds studied,allylic acetates were mostwidely used as precursors of(π-allyl)palladium intermediates.However,bases such as NaHmust be used to generate anions in this reaction.Recently,research on carrying out the palla-.

Low-complexity model predictive control of a four-level active neutral point clamped inverter without weighting factors

The four-level active neutral point clamped(ANPC)inverter has become increasingly widely used in the renewable energy indus-try since it offers one more voltage level without increasing the total number of active switches compared to the three-level ANPC inverter.The model predictive current control(MPCC)is a promising control method for multi-level inverters.However,the conven-tional MPCC suffers from high computational complexity and tedious weighting factor tuning in multi-level inverter applications.A low-complexity MPCC without weighting factors for a four-level ANPC inverter is proposed in this paper.The computational burden and voltage vector candidate set are reduced according to the relationship between voltage vector and neutral point voltage balance.The proposed MPCC shows excellent steady-state and dynamics performances while ensuring the neutral point voltage balancing.The efficacy of the proposed MPCC is verified by simulation and experimental results.