Dr. Subbarao and her coworkers first tested whether the human H5N1 mAbs could protect mice from severe H5N1 infection. Groups of five mice received either of two human H5N1 mAbs at one of three dosages or human mAbs against diphtheria or anthrax. One day later, the mice were exposed through their noses to lethal doses of H5N1 influenza virus.
All the control micethose receiving non-H5N1 mAbsrapidly developed severe illness and died within a week. In contrast, all the mice that received the first H5N1 mAb testedregardless of dosesurvived, while 80 percent of mice receiving the highest dose of the second H5N1 mAb survived. Additional tests showed that mice receiving either of the two protective H5N1 mAbs had levels of virus in the lungs that were 10 to 100 times lower than those in control mice, and little or no virus moved beyond the lungs.
The investigators also tested the therapeutic potential of the human H5N1 mAbs. Using blood products from influenza survivors is an old idea, the researchers note. During the flu pandemic of 1918-19, for example, physicians took serum from recovered flu patients and gave it to new victims; recent historical research indicates that those blood transfusions, when given early in the illness, sometimes saved recipients' lives.
In their study, Dr. Subbarao and her colleagues infected groups of mice with a lethal dose of an H5N1 virus that had circulated in Vietnam in 2004. A total of 60 mice were given one of the four H5N1 mAbs at 24, 48 or 72 hours after infection while a control group received non-influenza mAbs. All the mice in the control group died within 10 days of infection, while 58 of the 60 treated mice survived. All four H5N1 mAbs conferred robust protection. Most surprisingly, says Dr. Subbarao, the survival rate was excellent even when treatment was delayed for three days.
Spurred by these results, the NIAID inve
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
28-May-2007