title: Cross clade prophylactic and therapeutic efficacy of polyvalent equine immunoglobulin F(ab')2 against highly pathogenic avian influenza H5N1 in mice.
abstract: BACKGROUND
  Highly pathogenic avian influenza H5N1 virus (HPAI H5N1) has the potential to cause a new pandemic, which may lead to disasters in the world. However, we cannot predict the HPAI H5N1 strain that might cause the pandemic. Therefore, broad-spectrum prophylactic or therapeutic preparations for containment of a possible future pandemic are urgently needed. Polyvalent equine immunoglobulin F(ab')2 may be a promising candidate.
  
  
  METHODS
  We prepared four pepsin digested immunoglobulin F(ab')2 from the horses immunized with purified VNH5N1-Puerto Rico/8/34 (PR8)/CDC-RG (VNRG, Clade 1), A/Indonesia/05/2005(H5N1)-PR8-IBCDC-RG2 (INRG, Clade 2.1), and A/Anhui/01/2005(H5N1)-PR8-IBCDC-RG5 (AHRG, Clade 2.3.4) and PBS (negative control), respectively. The protective effect of the monovalent or polyvalent F(ab')2 against A/Ostrich/SZ/097/04 (clade 0) infection was determined by cytopathic effect (CPE) in cultured Madin-Darby canine kidney (MDCK) cells. The prophylactic and therapeutic efficacy of the polyvalent F(ab')2 was further evaluated by observing survival, weight loss and viral load when the polyvalent F(ab')2 was introduced into mice one day prior to-, three days post-lethal challenge with A/Ostrich/SZ/097/04.
  
  
  RESULTS
  The half neutralization doses (ND50) of purified monovalent equine F(ab')2 prepared by the VNRG, INRG or AHRG-immunized horses and polyvalent one against A/Ostrich/SZ/097/04 were 320, 1280, 1280 and 2560 in cultured MDCK cells, respectively. 10 μg polyvalent F(ab')2 could completely protect mice infected with 100 half lethal doses (LD50) of A/Ostrich/SZ/097/04 in preventive settings. In therapeutic settings, even when injected three days post lethal infection, mice were still completely protected, although 200 μg of polyvalent F(ab')2 was required.
  
  
  CONCLUSIONS
  Our work has provided experimental supports for testing the broad-spectrum protective efficacy of polyvalent equine immunoglobulin F(ab')2 for the future large trials.
authors: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors: Zhongpeng
authors: Z
authors: Zhao
authors: Fang
authors: F
authors: Yan
authors: Zhongwei
authors: Z
authors: Chen
authors: Deyan
authors: D
authors: Luo
authors: Yueqiang
authors: Y
authors: Duan
authors: Penghui
authors: P
authors: Yang
authors: Zhong
authors: Z
authors: Li
authors: Daxin
authors: D
authors: Peng
authors: Xiufan
authors: X
authors: Liu
authors: Xiliang
authors: X
authors: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D006736:Horses / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D007140:Immunoglobulin Fab Fragments; D007252:Influenza Vaccines