BackgroundGiven that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants.Methods/Principal FindingsWe selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy.Conclusions/SignificanceOur studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.

AIE, aggregation-induced emission; ATP, adenosine-5'-triphosphate; ATRP, atom transfer radical polymerization; BSA, bovine serum albumin; CBA, cystamine bisacrylamide; CC, Cytochrome C; CDDP, cisplatin; CT, computed tomography; DC, dendritic cell; DiI, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate; DOX, doxorubicin; dPG, dendritic polyglycerol; DTT, dithiothreitol; EAMA, 2-(N,N-diethylamino)ethyl methacrylate; EPR, enhanced permeability and retention; GrB, granzyme B; GSH, glutathione tripeptide; HA, hyaluronic acid; HAase, hyaluronidases; HCPT, 10-Hydroxycamptothecin; HEP, heparin; HPMC, hydroxypropylmethylcellulose; LBL, layer-by-layer; MTX, methotrexate; NCA, N-carboxyanhydride; OVA, ovalbumin; PAH, poly(allyl amine hydrochloride); PBA, phenylboronic acid; PCL, polycaprolactone; PDEAEMA, poly(2-diethylaminoethyl methacrylate); PDGF, platelet derived growth factor; PDPA, poly(2-(diisopropylamino)ethyl methacrylate); PDS, pyridyldisulfide; PEG, poly(ethylene glycol); PEGMA, polyethyleneglycol methacrylate; PEI, polyethyleneimine; PHEA, poly(hydroxyethyl acrylate); PHEMA, poly(2-(hydroxyethyl) methacrylate; PNIPAM, poly(N-isopropylacrylamide); PMAA, poly(methacrylic acid); PPDSMA, poly(2-(pyridyldisulfide)ethyl methacrylate); PTX, paclitaxel; PVA, poly(vinyl alcohol); QD, quantum dot; RAFT, reversible addition-fragmentation chain transfer; RGD, Arg-Gly-Asp peptide; ROP, ring-opening polymerization; ROS, reactive oxygen species; TMZ, temozolomide; TRAIL, tumor necrosis factor-related apoptosis inducing ligand; VEGF, vascular endothelial growth factor.

The pressure drop over a packed bed with sintered ore particles was studied experimentally. The sintered ore particles were characterized to determine their equivalent particle diameter, bed voidage, and sphericity. The pressure drop experiments were performed on unsorted and sieved particles with various size distributions for a superficial velocity up to 2.4 m/s, covering flow regimes from laminar to turbulent. It was shown that the Ergun equation underestimates the pressure drop for such highly irregular-shaped particles by about 40%. The measured modified friction factor was well correlated to a scaled Ergun equation, which was verified to be valid for the modified particle Reynolds number up to 12 000 toward design and optimization of vertically arranged sinter coolers for waste heat recovery.

Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype has caused devastating damage to poultry flocks and sporadic human H5N1 infections. There is concern that this virus subtype may gain transmissibility and become pandemic. Rapid diagnosis and surveillance for H5N1 subtype viruses are critical for the control of H5N1 infection. In this study, we report a robust antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) based on H5-and N1-specific monoclonal antibodies (