Prevention and treatment of lethal influenza A virus bronchopneumonia in mice by monoclonal antibody against haemagglutinin stem region.
The protective properties of monoclonal antibody (MoAb) C179 directed to the stem region of haemagglutinin (HA) H2 that possessed fusion-inhibition and unique broad cross-neutralizing activities were examined in a mouse model. The MoAb efficiently protected mice against a lethal challenge with pneumovirulent human (H1) and avian (H2) strains of influenza A virus. Survival rates in mice that received intraperitonealy (i.p.) 1000 micrograms of the MoAb per mouse a day before the virus challenge were 90% for H1 and 100% for H2 strain. The dose of the MoAb of 100 micrograms per mouse significantly decreased mortality in mice. Moreover, the MoAb was also efficient in treatment of lethal bronhopneumonia caused by H2 influenza virus. The survival rate in mice that received 1000 micrograms of the MoAb per mouse 2 days after the virus challenge was 90%, while that in the control group was 30% only. These results indicate that the MoAb was effective in protection of animals against lethal influenza A infection without significant difference between H1 and H2 subtypes. The MoAb exerted significant effect in treatment of mice infected with H2 influenza virus. Thus, these data allow to suggest that the stem region of HA might be a potential target for prevention of influenza virus infection and antiviral therapy.
Lipatov
A S
AS
D.I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Moscow, Russia.
Gitelman
A K
AK
Smirnov YuA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001996:Bronchopneumonia / Q000517:prevention & control / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D006389:Hemagglutinins, Viral / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000628:therapy*; D011024:Pneumonia, Viral / Q000517:prevention & control / Q000628:therapy*; D011897:Random Allocation; D013997:Time Factors
D000911:Antibodies, Monoclonal; D006389:Hemagglutinins, Viral